butalbital/aspirin/caffeine/codeine (Rx)

Tension Headache

1-2 tab/cap PO q4hr; not to exceed 6 tabs/caps per day

To discontinue therapy, decrease dose by 25% to 50% every 2-4 days; monitor for symptoms/signs of withdrawal; if withdrawal symptoms occur, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both; do not abruptly discontinue therapy in a physically dependent patient

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids and butalbital, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options [e.g., non-opioid, non-barbiturate analgesics] have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia

Dosing Considerations

Use lowest effective dosage for shortest duration consistent with individual patient treatment goals

Initiate dosing regimen for each patient individually, taking into account patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse

Evidence supporting efficacy and safety of drug in treatment of multiple recurrent headaches is unavailable

The FDA has recommended that codeine not be used in children <12 years and all pediatric patients undergoing tonsillectomy and/or adenoidectomy

Tension Headache

<16 years: Safety and efficacy not established

≥16 years: 1-2 tab/cap PO q4hr; not to exceed 6 tabs/caps per day

To discontinue therapy, decrease dose by 25% to 50% every 2-4 days; monitor for symptoms/signs of withdrawal; if withdrawal symptoms occur, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both; do not abruptly discontinue therapy in a physically dependent patient

Use caution; barbiturates not recommended in the elderly

Tension Headache

1-2 tab/cap PO q4hr; not to exceed 6 tabs/caps per day

To discontinue therapy, decrease dose by 25% to 50% every 2-4 days; monitor for symptoms/signs of withdrawal; if withdrawal symptoms occur, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both; do not abruptly discontinue therapy in a physically dependent patient

Contraindicated (9)

• abrocitinib

  abrocitinib and aspirin both increase anticoagulation. Contraindicated. Antiplatelet drugs, except for low-dose aspirin (=81 mg qDay), during the first 3 months of treatment are contraindicated.

• alvimopan

  alvimopan, codeine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• dichlorphenamide

  dichlorphenamide increases levels of aspirin by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

• doravirine

  butalbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• fezolinetant

  caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• isocarboxazid

  isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• linezolid

  linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• mifepristone

  aspirin, mifepristone. Other (see comment). Contraindicated. Comment: Aspirin induced antiplatelet activity may induce excessive bleeding after an abortion w/mifepristone (RU 486).

• phenelzine

  phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

Serious - Use Alternative (116)

• abemaciclib

  butalbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• acrivastine

  acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alosetron

  butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• alpelisib

  butalbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

• amisulpride

  amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.

• antithrombin alfa

  butalbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

• antithrombin III

  butalbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

• argatroban

  butalbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

• asenapine

  asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• avapritinib

  avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bemiparin

  butalbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

• benazepril

  aspirin, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bivalirudin

  butalbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

• bremelanotide

  bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexpiprazole

  brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brigatinib

  butalbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

• brimonidine

  brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine

  buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine, long-acting injection and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• butorphanol

  butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• calcium/magnesium/potassium/sodium oxybates

  butalbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• calcium/magnesium/potassium/sodium oxybates

  codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• capivasertib

  butalbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.

• caplacizumab

  caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• captopril

  aspirin, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• clonidine

  clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• copanlisib

  butalbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• dacomitinib

  dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dalteparin

  butalbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.

• daridorexant

  butalbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• deflazacort

  butalbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• diazepam intranasal

  diazepam intranasal, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• dihydroergotamine

  butalbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  butalbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dipyridamole

  caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
  
  butalbital decreases levels of dipyridamole by increasing metabolism. Contraindicated.

• dronedarone

  butalbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• givosiran

  givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

• duloxetine

  butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• duvelisib

  butalbital will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• elacestrant

  butalbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eluxadoline

  codeine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• enalapril

  aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• enoxaparin

  butalbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  butalbital will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ergotamine

  butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin base

  butalbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  butalbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  butalbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  butalbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• everolimus

  butalbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fedratinib

  butalbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• fentanyl

  fentanyl and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  fentanyl intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl intranasal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl iontophoretic transdermal system

  fentanyl iontophoretic transdermal system and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl iontophoretic transdermal system and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  fentanyl transmucosal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transmucosal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fexinidazole

  butalbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• fosinopril

  aspirin, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• givosiran

  givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• finerenone

  butalbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fondaparinux

  butalbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

• fostamatinib

  butalbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fruquintinib

  butalbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.

• ganaxolone

  butalbital will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• glasdegib

  butalbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• heparin

  butalbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

• hydrocodone

  hydrocodone, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• ibuprofen

  ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.
  
  ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

• ibuprofen IV

  ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.
  
  ibuprofen IV decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

• infigratinib

  butalbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• iobenguane I 131

  caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• isocarboxazid

  isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• isocarboxazid

  isocarboxazid, butalbital. Other (see comment). Contraindicated. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.

• istradefylline

  butalbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• ivosidenib

  butalbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ketorolac

  aspirin, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

• ketorolac intranasal

  aspirin, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

• larotrectinib

  butalbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• lefamulin

  butalbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  butalbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  lemborexant, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

• lenacapavir

  butalbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  butalbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lesinurad

  aspirin decreases effects of lesinurad by unspecified interaction mechanism. Avoid or Use Alternate Drug. Aspirin at doses >325 mg/day may decrease lesinurad efficacy. Aspirin doses 325 mg/day or less (ie, for cardiovascular event prophylaxis) does not decrease lesinurad efficacy and can be coadministered.

• linezolid

  linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• lisinopril

  aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lovastatin

  butalbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumateperone

  butalbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  butalbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  butalbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.
  
  aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

• measles, mumps, rubella and varicella vaccine, live

  aspirin, measles, mumps, rubella and varicella vaccine, live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• mestranol

  butalbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

• methotrexate

  aspirin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.

• methoxyflurane

  butalbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

• methylene blue

  methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
  
  methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• metoclopramide intranasal

  codeine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
  
  butalbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• midostaurin

  butalbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  aspirin will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mitotane

  aspirin will decrease the level or effect of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• moexipril

  aspirin, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• nalbuphine

  nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• mobocertinib

  butalbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• naldemedine

  butalbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• neratinib

  butalbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• nirogacestat

  butalbital will decrease the level or effect of nirogacestat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• olopatadine intranasal

  codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  butalbital and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  butalbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• ozanimod

  ozanimod and codeine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
  
  ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• omaveloxolone

  butalbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• regadenoson

  caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

Monitor Closely (702)

• abciximab

  aspirin, abciximab. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• abiraterone

  abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
  
  butalbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• acalabrutinib

  acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
  
  butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• acebutolol

  acebutolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• acebutolol

  butalbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• acrivastine

  acrivastine and butalbital both increase sedation. Use Caution/Monitor.

• albuterol

  codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and caffeine both decrease sedation. Use Caution/Monitor.

• aceclofenac

  aceclofenac and aspirin both increase anticoagulation. Use Caution/Monitor.
  
  aceclofenac and aspirin both increase serum potassium. Use Caution/Monitor.

• alfentanil

  alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  alfentanil and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and alfentanil both increase sedation. Use Caution/Monitor.

• acemetacin

  acemetacin and aspirin both increase anticoagulation. Use Caution/Monitor.
  
  acemetacin and aspirin both increase serum potassium. Use Caution/Monitor.

• acetazolamide

  acetazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.
  
  acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• agrimony

  aspirin and agrimony both increase anticoagulation. Use Caution/Monitor.

• albuterol

  aspirin increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfalfa

  aspirin and alfalfa both increase anticoagulation. Use Caution/Monitor.

• alfuzosin

  aspirin decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aliskiren

  aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

• almotriptan

  butalbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alprazolam

  alprazolam and codeine both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alprazolam

  butalbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and alprazolam both increase sedation. Use Caution/Monitor.

• amitriptyline

  amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alteplase

  aspirin, alteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• American ginseng

  aspirin and American ginseng both increase anticoagulation. Use Caution/Monitor.

• amiloride

  amiloride and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• amiodarone

  butalbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• amisulpride

  amisulpride and butalbital both increase sedation. Use Caution/Monitor.

• amitriptyline

  codeine and amitriptyline both increase sedation. Use Caution/Monitor.

• amitriptyline

  butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.

• amlodipine

  butalbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amobarbital

  amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  amobarbital and butalbital both increase sedation. Use Caution/Monitor.

• amoxapine

  amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and amoxapine both increase sedation. Use Caution/Monitor.
  
  codeine and amoxapine both increase sedation. Use Caution/Monitor.

• amoxicillin

  amoxicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  amoxicillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• arformoterol

  arformoterol and caffeine both decrease sedation. Use Caution/Monitor.

• ampicillin

  ampicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• anagrelide

  aspirin, anagrelide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.
  
  anagrelide, aspirin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.

• antithrombin alfa

  antithrombin alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin alfa. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• antithrombin III

  antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin III. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• apixaban

  aspirin and apixaban both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspiriin. Avoid coadministration with chronic use of higher dose aspirin. In 1 trial (APPRAISE-2), therapy was terminated because of significantly increased bleeding when apixaban was administered with dual antiplatelet therapy (eg, aspirin plus clopidogrel) compared with single antiplatelet treatment

• apomorphine

  butalbital and apomorphine both increase sedation. Use Caution/Monitor.
  
  codeine and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

  butalbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• arformoterol

  butalbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• argatroban

  argatroban and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, argatroban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• aripiprazole

  aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and aripiprazole both increase sedation. Use Caution/Monitor.
  
  butalbital and aripiprazole both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• armodafinil

  butalbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil and caffeine both decrease sedation. Use Caution/Monitor.

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• asenapine

  aspirin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  asenapine and butalbital both increase sedation. Use Caution/Monitor.

• atenolol

  atenolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• asenapine transdermal

  asenapine transdermal and butalbital both increase sedation. Use Caution/Monitor.

• atenolol

  butalbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• atogepant

  butalbital will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

• atorvastatin

  butalbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avanafil

  butalbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness

• avapritinib

  avapritinib and butalbital both increase sedation. Use Caution/Monitor.

• azelastine

  azelastine and codeine both increase sedation. Use Caution/Monitor.
  
  azelastine and butalbital both increase sedation. Use Caution/Monitor.

• azficel-T

  azficel-T, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking aspirin may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of aspirin is not recommended. .

• baclofen

  baclofen and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and baclofen both increase sedation. Use Caution/Monitor.

• azilsartan

  aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• bazedoxifene/conjugated estrogens

  butalbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• belladonna and opium

  codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belladonna and opium

  butalbital and belladonna and opium both increase sedation. Use Caution/Monitor.

• benperidol

  benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belumosudil

  butalbital will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.

• bemiparin

  bemiparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• benazepril

  butalbital increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor.
  
  benazepril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

• bendroflumethiazide

  aspirin increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benperidol

  codeine and benperidol both increase sedation. Use Caution/Monitor.
  
  butalbital and benperidol both increase sedation. Use Caution/Monitor.

• benzphetamine

  caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• betaxolol

  betaxolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• brompheniramine

  brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• betrixaban

  aspirin, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bisoprolol

  butalbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bortezomib

  butalbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexanolone

  brexanolone, butalbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
  
  brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• bimatoprost

  bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• brexpiprazole

  brexpiprazole and codeine both increase sedation. Use Caution/Monitor.

• bisoprolol

  bisoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• bivalirudin

  bivalirudin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, bivalirudin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• brimonidine

  brimonidine and butalbital both increase sedation. Use Caution/Monitor.

• brinzolamide

  brinzolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• brivaracetam

  brivaracetam and codeine both increase sedation. Use Caution/Monitor.
  
  brivaracetam and butalbital both increase sedation. Use Caution/Monitor.

• brompheniramine

  brompheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  brompheniramine and codeine both increase sedation. Use Caution/Monitor.

• budesonide

  butalbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bumetanide

  aspirin increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• buprenorphine

  buprenorphine and codeine both increase sedation. Use Caution/Monitor.

• buprenorphine

  butalbital and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• buprenorphine, long-acting injection

  butalbital increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  butalbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

• butabarbital

  butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bupropion

  butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .
  
  bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.

• buspirone

  butalbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  butabarbital and codeine both increase sedation. Use Caution/Monitor.

• butabarbital

  butabarbital and butalbital both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butorphanol

  butorphanol and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and butorphanol both increase sedation. Use Caution/Monitor.
  
  butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• caffeine

  butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• candesartan

  candesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• cannabidiol

  butalbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

• captopril

  captopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, elderly or volume depleted individuals.

• carbenoxolone

  aspirin increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and codeine both increase sedation. Use Caution/Monitor.

• captopril

  butalbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

• carbamazepine

  butalbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and butalbital both increase sedation. Use Caution/Monitor.

• carisoprodol

  carisoprodol and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and carisoprodol both increase sedation. Use Caution/Monitor.

• carvedilol

  butalbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  carvedilol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• celecoxib

  aspirin and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  aspirin and celecoxib both increase anticoagulation. Use Caution/Monitor.

• celiprolol

  celiprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• cenobamate

  cenobamate, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

  chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorothiazide

  aspirin increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chloral hydrate both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• chloroquine

  chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• chlorpheniramine

  chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
  
  codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorpropamide

  aspirin increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• chlorthalidone

  aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorzoxazone

  chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• choline magnesium trisalicylate

  aspirin and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

• cilostazol

  aspirin, cilostazol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  butalbital will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cimetidine

  cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinnamon

  aspirin and cinnamon both increase anticoagulation. Use Caution/Monitor.

• cinacalcet

  cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnarizine

  cinnarizine and butalbital both increase sedation. Use Caution/Monitor.
  
  cinnarizine and codeine both increase sedation. Use Caution/Monitor.
  
  cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ciprofloxacin

  aspirin decreases levels of ciprofloxacin by Other (see comment). Use Caution/Monitor. Comment: Buffered aspirin may decrease absorption of quinolones. Consider administering 2 hr before or 6 hr after, buffered aspirin administration.
  
  ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

• citalopram

  citalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clemastine

  clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clemastine

  clemastine and butalbital both increase sedation. Use Caution/Monitor.
  
  clemastine and codeine both increase sedation. Use Caution/Monitor.

• clobazam

  codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clomipramine

  butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  clomipramine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.
  
  butalbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clomipramine

  codeine and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clonazepam

  clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clopidogrel

  aspirin, clopidogrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• clonazepam

  butalbital and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam and codeine both increase sedation. Use Caution/Monitor.

• clopidogrel

  butalbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  clorazepate and codeine both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clorazepate

  butalbital and clorazepate both increase sedation. Use Caution/Monitor.

• clozapine

  clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clozapine

  codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and clozapine both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cocaine topical

  cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• codeine

  butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• colchicine

  butalbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyclizine

  cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• collagenase clostridium histolyticum

  aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

• conivaptan

  butalbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  butalbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens, vaginal

  butalbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cordyceps

  aspirin and cordyceps both increase anticoagulation. Use Caution/Monitor.

• cortisone

  aspirin, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.
  
  butalbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyclizine

  cyclizine and codeine both increase sedation. Use Caution/Monitor.
  
  cyclizine and butalbital both increase sedation. Use Caution/Monitor.

• cyclopenthiazide

  aspirin increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cyclobenzaprine

  butalbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.

• cyclosporine

  butalbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
  
  cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and butalbital both increase sedation. Use Caution/Monitor.

• deferasirox

  deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• dabigatran

  dabigatran and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin

• dalteparin

  dalteparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, dalteparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• dantrolene

  dantrolene and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and dantrolene both increase sedation. Use Caution/Monitor.

• daridorexant

  butalbital and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  butalbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  deferasirox, aspirin. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.

• defibrotide

  defibrotide increases effects of aspirin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  aspirin, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• desflurane

  desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• dasatinib

  butalbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• desipramine

  codeine and desipramine both increase sedation. Use Caution/Monitor.
  
  butalbital and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• desirudin

  aspirin, desirudin. Either increases levels of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• dexchlorpheniramine

  dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• desvenlafaxine

  desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  butalbital and deutetrabenazine both increase sedation. Use Caution/Monitor.

• deutetrabenazine

  codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  butalbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• dexchlorpheniramine

  dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmethylphenidate

  caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.

• dextroamphetamine

  caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.

• dextromoramide

  dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diclofenac

  aspirin and diclofenac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diclofenac both increase serum potassium. Use Caution/Monitor.

• dexfenfluramine

  butalbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  butalbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  butalbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextromoramide

  butalbital and dextromoramide both increase sedation. Use Caution/Monitor.
  
  codeine and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  butalbital and diamorphine both increase sedation. Use Caution/Monitor.
  
  codeine and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  diazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  butalbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
  
  diazepam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dicloxacillin

  dicloxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• diethylpropion

  caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.
  
  codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diethylpropion

  butalbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difenoxin hcl

  difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and codeine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and butalbital both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  butalbital and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diflunisal

  aspirin and diflunisal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diflunisal both increase serum potassium. Use Caution/Monitor.

• digoxin

  aspirin and digoxin both increase serum potassium. Use Caution/Monitor.

• diltiazem

  butalbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dimenhydrinate

  dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.

• dimenhydrinate

  dimenhydrinate and butalbital both increase sedation. Use Caution/Monitor.

• diphenhydramine

  diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenhydramine

  diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine and butalbital both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  butalbital and dipipanone both increase sedation. Use Caution/Monitor.
  
  codeine and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipyridamole

  aspirin, dipyridamole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• dobutamine

  dobutamine and caffeine both decrease sedation. Use Caution/Monitor.

• dobutamine

  butalbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dong quai

  aspirin and dong quai both increase anticoagulation. Use Caution/Monitor.

• dopamine

  caffeine and dopamine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  aspirin increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

• dosulepin

  butalbital and dosulepin both increase sedation. Use Caution/Monitor.
  
  codeine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• doxazosin

  aspirin decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• doxepin

  butalbital and doxepin both increase sedation. Use Caution/Monitor.
  
  codeine and doxepin both increase sedation. Use Caution/Monitor.

• doxycycline

  butalbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

• doxylamine

  doxylamine and codeine both increase sedation. Use Caution/Monitor.

• doxylamine

  butalbital and doxylamine both increase sedation. Use Caution/Monitor.

• dronabinol

  butalbital will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• droperidol

  codeine and droperidol both increase sedation. Use Caution/Monitor.
  
  butalbital and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• drospirenone

  drospirenone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• droxidopa

  caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• edoxaban

  edoxaban, aspirin. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• elagolix

  butalbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eletriptan

  butalbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eltrombopag

  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enalapril

  enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

• ephedrine

  ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• enoxaparin

  enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI
  
  aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• epinephrine

  epinephrine and caffeine both decrease sedation. Use Caution/Monitor.

• ephedrine

  aspirin increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  aspirin increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine inhaled

  caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  butalbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• epoprostenol

  aspirin and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• esketamine intranasal

  esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

• erlotinib

  butalbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eprosartan

  eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• eptifibatide

  aspirin, eptifibatide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• escitalopram

  escitalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• escitalopram

  butalbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• esketamine intranasal

  esketamine intranasal, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  aspirin decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  esmolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• estazolam

  estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  estazolam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and estazolam both increase sedation. Use Caution/Monitor.

• ethacrynic acid

  aspirin increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

  ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• estradiol

  butalbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethanol

  codeine and ethanol both increase sedation. Use Caution/Monitor.

• estradiol vaginal

  butalbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  butalbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  butalbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethanol

  butalbital and ethanol both increase sedation. Use Caution/Monitor.

• ethinylestradiol

  ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• ethotoin

  butalbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etodolac

  aspirin and etodolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and etodolac both increase serum potassium. Use Caution/Monitor.

• etomidate

  etomidate and codeine both increase sedation. Use Caution/Monitor.
  
  etomidate and butalbital both increase sedation. Use Caution/Monitor.

• etonogestrel

  butalbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• etravirine

  butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• felodipine

  butalbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenbufen

  aspirin and fenbufen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenbufen both increase serum potassium. Use Caution/Monitor.

• fenfluramine

  caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fennel

  aspirin and fennel both increase anticoagulation. Use Caution/Monitor.

• fexinidazole

  fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• fenoprofen

  aspirin and fenoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenoprofen both increase serum potassium. Use Caution/Monitor.

• fesoterodine

  butalbital will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• feverfew

  aspirin and feverfew both increase anticoagulation. Use Caution/Monitor.

• fish oil

  fish oil, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• fish oil triglycerides

  fish oil triglycerides will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flibanserin

  codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• flibanserin

  butalbital and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fludrocortisone

  butalbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• fluoxetine

  fluoxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine

• fluphenazine

  fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  butalbital and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• flurazepam

  butalbital and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam and codeine both increase sedation. Use Caution/Monitor.

• flurbiprofen

  aspirin and flurbiprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and flurbiprofen both increase serum potassium. Use Caution/Monitor.

• fluvoxamine

  fluvoxamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding SSRIs inhib. serotonin uptake by platelets.
  
  fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• fondaparinux

  fondaparinux and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• formoterol

  formoterol and caffeine both decrease sedation. Use Caution/Monitor.

• formoterol

  butalbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• forskolin

  aspirin and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosamprenavir

  butalbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosinopril

  fosinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

• furosemide

  aspirin increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• gabapentin

  gabapentin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• fosaprepitant

  butalbital will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosphenytoin

  butalbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• gabapentin

  gabapentin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  gabapentin enacarbil, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  gabapentin enacarbil, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  butalbital and ganaxolone both increase sedation. Use Caution/Monitor.
  
  codeine and ganaxolone both increase sedation. Use Caution/Monitor.

• garlic

  aspirin and garlic both increase anticoagulation. Use Caution/Monitor.

• gentamicin

  aspirin increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ginger

  aspirin and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  aspirin and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• glecaprevir/pibrentasvir

  butalbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

• glimepiride

  aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glipizide

  aspirin increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glyburide

  aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• green tea

  green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.
  
  green tea increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.

• griseofulvin

  griseofulvin decreases levels of aspirin by unknown mechanism. Use Caution/Monitor.

• guselkumab

  guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• gotu kola

  gotu kola increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hydromorphone

  hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• guanfacine

  butalbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• haloperidol

  butalbital and haloperidol both increase sedation. Use Caution/Monitor.

• hawthorn

  hawthorn increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hemin

  butalbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• heparin

  heparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, heparin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• hops

  hops increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• horse chestnut seed

  aspirin and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

• hyaluronidase

  aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  aspirin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocortisone

  butalbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• hydromorphone

  codeine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  butalbital and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ibrutinib

  ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• hydroxyprogesterone caproate (DSC)

  butalbital will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and codeine both increase sedation. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and butalbital both increase sedation. Use Caution/Monitor.

• ibuprofen

  aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.

• ibuprofen IV

  aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

• icosapent

  icosapent, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time. Periodically monitor if coadministered with other drugs that affect bleeding.

• ifosfamide

  butalbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  butalbital increases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• iloperidone

  butalbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  codeine and iloperidone both increase sedation. Use Caution/Monitor.
  
  butalbital and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• imatinib

  imatinib, aspirin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

• imipramine

  imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• imipramine

  butalbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and imipramine both increase sedation. Use Caution/Monitor.
  
  codeine and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• indapamide

  aspirin increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• indinavir

  butalbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indomethacin

  aspirin and indomethacin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and indomethacin both increase serum potassium. Use Caution/Monitor.

• insulin aspart

  aspirin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin aspart protamine/insulin aspart

  aspirin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec

  aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

• insulin detemir

  aspirin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glargine

  aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glulisine

  aspirin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  aspirin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin isophane human/insulin regular human

  aspirin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro

  aspirin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro protamine/insulin lispro

  aspirin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin NPH

  aspirin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin regular human

  aspirin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• irbesartan

  irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• isoniazid

  isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• isoproterenol

  codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ixabepilone

  butalbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketotifen, ophthalmic

  ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ketoprofen

  aspirin and ketoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketoprofen both increase serum potassium. Use Caution/Monitor.

• ketamine

  ketamine and codeine both increase sedation. Use Caution/Monitor.

• kava

  kava increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  ketamine and butalbital both increase sedation. Use Caution/Monitor.

• ketoconazole

  ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• ketorolac

  aspirin and ketorolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac both increase serum potassium. Use Caution/Monitor.

• ketorolac intranasal

  aspirin and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

• ketotifen, ophthalmic

  codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  butalbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• labetalol

  aspirin decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  labetalol and aspirin both increase serum potassium. Use Caution/Monitor.

• lasmiditan

  lasmiditan, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprost

  latanoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lapatinib

  butalbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lasmiditan

  lasmiditan, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprostene bunod ophthalmic

  latanoprostene bunod ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lemborexant

  lemborexant, codeine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• letermovir

  letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  aspirin increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• levamlodipine

  butalbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levorphanol

  levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levomilnacipran

  levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levoketoconazole

  levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  butalbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• levorphanol

  codeine and levorphanol both increase sedation. Use Caution/Monitor.
  
  butalbital and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

• lidocaine

  butalbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• lisdexamfetamine

  caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisdexamfetamine

  butalbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofepramine

  lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisinopril

  lisinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

• lithium

  aspirin increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

• lofepramine

  codeine and lofepramine both increase sedation. Use Caution/Monitor.
  
  butalbital and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  butalbital and lofexidine both increase sedation. Use Caution/Monitor.
  
  codeine and lofexidine both increase sedation. Use Caution/Monitor.
  
  lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lopinavir

  lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loprazolam

  butalbital and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam and codeine both increase sedation. Use Caution/Monitor.

• loratadine

  butalbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lorazepam

  lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  lorazepam and codeine both increase sedation. Use Caution/Monitor.

• lorazepam

  butalbital and lorazepam both increase sedation. Use Caution/Monitor.

• lormetazepam

  lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lorcaserin

  lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• lormetazepam

  lormetazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and lormetazepam both increase sedation. Use Caution/Monitor.

• lornoxicam

  aspirin and lornoxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and lornoxicam both increase serum potassium. Use Caution/Monitor.

• losartan

  losartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• loxapine

  butalbital and loxapine both increase sedation. Use Caution/Monitor.
  
  codeine and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  butalbital and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumefantrine

  butalbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• maprotiline

  maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lurasidone

  lurasidone, butalbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  butalbital and maprotiline both increase sedation. Use Caution/Monitor.
  
  codeine and maprotiline both increase sedation. Use Caution/Monitor.

• maraviroc

  butalbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• marijuana

  marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and marijuana both increase sedation. Use Caution/Monitor.

• marijuana

  butalbital and marijuana both increase sedation. Use Caution/Monitor.

• melatonin

  melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meclofenamate

  aspirin and meclofenamate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meclofenamate both increase serum potassium. Use Caution/Monitor.

• mefenamic acid

  aspirin and mefenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and mefenamic acid both increase serum potassium. Use Caution/Monitor.

• melatonin

  melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.
  
  codeine and melatonin both increase sedation. Use Caution/Monitor.
  
  butalbital and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  aspirin and meloxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meloxicam both increase serum potassium. Use Caution/Monitor.

• meperidine

  butalbital and meperidine both increase sedation. Use Caution/Monitor.
  
  codeine and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meprobamate

  meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and meprobamate both increase sedation. Use Caution/Monitor.
  
  codeine and meprobamate both increase sedation. Use Caution/Monitor.

• mesalamine

  mesalamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.

• metaproterenol

  metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.

• mestranol

  butalbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metaproterenol

  aspirin increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaproterenol

  butalbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methadone

  methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.

• methazolamide

  methazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• metaxalone

  butalbital and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and codeine both increase sedation. Use Caution/Monitor.

• methadone

  butalbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and methadone both increase sedation. Use Caution/Monitor.
  
  codeine and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  butalbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

  butalbital and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and codeine both increase sedation. Use Caution/Monitor.

• methotrexate

  caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.

• methyclothiazide

  aspirin increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• methylenedioxymethamphetamine

  caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylphenidate

  caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• methylprednisolone

  butalbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• metolazone

  aspirin increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metoprolol

  butalbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• mexiletine

  butalbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• midazolam

  midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  midazolam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and midazolam both increase sedation. Use Caution/Monitor.

• metoprolol

  metoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• midodrine

  caffeine and midodrine both decrease sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  midazolam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  butalbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• milnacipran

  milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• mirabegron

  mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  butalbital and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mirtazapine

  codeine and mirtazapine both increase sedation. Use Caution/Monitor.

• modafinil

  caffeine and modafinil both decrease sedation. Use Caution/Monitor.

• mistletoe

  aspirin increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• modafinil

  codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moexipril

  moexipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

• morphine

  butalbital and morphine both increase sedation. Use Caution/Monitor.
  
  codeine and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  butalbital and motherwort both increase sedation. Use Caution/Monitor.
  
  codeine and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxisylyte

  aspirin decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• moxonidine

  moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxonidine

  butalbital and moxonidine both increase sedation. Use Caution/Monitor.
  
  codeine and moxonidine both increase sedation. Use Caution/Monitor.

• mycophenolate

  aspirin will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  butalbital and nabilone both increase sedation. Use Caution/Monitor.
  
  codeine and nabilone both increase sedation. Use Caution/Monitor.
  
  nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nabumetone

  aspirin and nabumetone both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and nabumetone both increase serum potassium. Use Caution/Monitor.

• nalbuphine

  nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nadolol

  nadolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nafcillin

  nafcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  nafcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• nalbuphine

  codeine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  butalbital and nalbuphine both increase sedation. Use Caution/Monitor.

• naproxen

  aspirin and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and naproxen both increase serum potassium. Use Caution/Monitor.

• nateglinide

  butalbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nebivolol

  nebivolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nefazodone

  nefazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• nelfinavir

  butalbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nettle

  aspirin increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nicardipine

  butalbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  butalbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nisoldipine

  butalbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nitazoxanide

  nitazoxanide, aspirin. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

• nitroglycerin rectal

  aspirin will increase the level or effect of nitroglycerin rectal by Other (see comment). Use Caution/Monitor. The pharmacological effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

• nitroglycerin sublingual

  aspirin increases effects of nitroglycerin sublingual by additive vasodilation. Use Caution/Monitor. Vasodilatory and hemodynamic effects of NTG may be enhanced by coadministration with aspirin (additive effect desirable for emergent treatment).

• norepinephrine

  norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norgestrel

  butalbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

• nortriptyline

  nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olanzapine

  olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olmesartan

  olmesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• nortriptyline

  codeine and nortriptyline both increase sedation. Use Caution/Monitor.

• nortriptyline

  butalbital and nortriptyline both increase sedation. Use Caution/Monitor.

• olanzapine

  butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  codeine and olanzapine both increase sedation. Use Caution/Monitor.
  
  butalbital and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  oliceridine, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  butalbital will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.
  
  oliceridine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• omega 3 carboxylic acids

  omega 3 carboxylic acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

• omega 3 fatty acids

  omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• omeprazole

  butalbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• opium tincture

  opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and opium tincture both increase sedation. Use Caution/Monitor.

• opium tincture

  butalbital and opium tincture both increase sedation. Use Caution/Monitor.

• oxazepam

  oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orphenadrine

  orphenadrine and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and orphenadrine both increase sedation. Use Caution/Monitor.

• osilodrostat

  butalbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

• ospemifene

  aspirin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxacillin

  oxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  oxacillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• oxaprozin

  aspirin and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and oxaprozin both increase serum potassium. Use Caution/Monitor.

• oxazepam

  oxazepam and codeine both increase sedation. Use Caution/Monitor.

• oxazepam

  butalbital and oxazepam both increase sedation. Use Caution/Monitor.

• oxycodone

  oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and oxycodone both increase sedation. Use Caution/Monitor.
  
  butalbital and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and oxymorphone both increase sedation. Use Caution/Monitor.
  
  codeine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  butalbital and paliperidone both increase sedation. Use Caution/Monitor.
  
  codeine and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• panax ginseng

  aspirin and panax ginseng both increase anticoagulation. Use Caution/Monitor.

• papaveretum

  papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaveretum

  butalbital and papaveretum both increase sedation. Use Caution/Monitor.
  
  codeine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  butalbital and papaverine both increase sedation. Use Caution/Monitor.
  
  codeine and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  aspirin and parecoxib both increase serum potassium. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  aspirin and parecoxib both increase anticoagulation. Use Caution/Monitor.

• paroxetine

  paroxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• passion flower

  passion flower increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• pau d'arco

  aspirin and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• pazopanib

  butalbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pefloxacin

  pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pegaspargase

  pegaspargase increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• peginterferon alfa 2b

  peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegvisomant

  codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• penbutolol

  butalbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  penbutolol and aspirin both increase serum potassium. Use Caution/Monitor.

• penicillin G aqueous

  penicillin G aqueous, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  penicillin G aqueous, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• pentazocine

  codeine and pentazocine both increase sedation. Use Caution/Monitor.
  
  butalbital and pentazocine both increase sedation. Use Caution/Monitor.
  
  pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pentobarbital

  butalbital and pentobarbital both increase sedation. Use Caution/Monitor.
  
  pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pentobarbital and codeine both increase sedation. Use Caution/Monitor.

• perampanel

  perampanel and codeine both increase sedation. Use Caution/Monitor.

• perphenazine

  perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• perindopril

  perindopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin,in elderly or volume depleted individuals.

• perphenazine

  butalbital and perphenazine both increase sedation. Use Caution/Monitor.

• perphenazine

  codeine and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenindione

  phenindione and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• phenobarbital

  phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenobarbital

  phenobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and phenobarbital both increase sedation. Use Caution/Monitor.

• phenoxybenzamine

  aspirin decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phentermine

  caffeine and phentermine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phentolamine

  aspirin decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phenylephrine

  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• phenylephrine

  butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
  
  caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  butalbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pholcodine

  pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pholcodine

  codeine and pholcodine both increase sedation. Use Caution/Monitor.

• pholcodine

  butalbital and pholcodine both increase sedation. Use Caution/Monitor.

• phytoestrogens

  aspirin and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

• pimozide

  codeine and pimozide both increase sedation. Use Caution/Monitor.
  
  butalbital and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pindolol

  pindolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pirbuterol

  pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• pirbuterol

  aspirin increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pirbuterol

  butalbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• piroxicam

  aspirin and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and piroxicam both increase serum potassium. Use Caution/Monitor.

• pitolisant

  butalbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• pivmecillinam

  pivmecillinam, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  pivmecillinam, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• polatuzumab vedotin

  butalbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• potassium acid phosphate

  aspirin and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  aspirin and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

• potassium iodide

  potassium iodide and aspirin both increase serum potassium. Use Caution/Monitor.

• prasugrel

  aspirin, prasugrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• prazosin

  aspirin decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  butalbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• prednisone

  aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.
  
  butalbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pregabalin

  pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  pregabalin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primidone

  primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• prochlorperazine

  prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promethazine

  promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• propranolol

  propranolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• primidone

  primidone and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

  butalbital and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  codeine and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine and butalbital both increase sedation. Use Caution/Monitor.
  
  promethazine and codeine both increase sedation. Use Caution/Monitor.

• propafenone

  butalbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.

• propofol

  propofol and codeine both increase sedation. Use Caution/Monitor.

• propofol

  propofol and butalbital both increase sedation. Use Caution/Monitor.

• propranolol

  butalbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• propylhexedrine

  caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  protamine and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• protriptyline

  protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protriptyline

  butalbital and protriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and protriptyline both increase sedation. Use Caution/Monitor.

• quazepam

  quazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  butalbital and quetiapine both increase sedation. Use Caution/Monitor.
  
  codeine and quetiapine both increase sedation. Use Caution/Monitor.
  
  quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinapril

  quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

• rasagiline

  rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

• quinidine

  quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ramelteon

  butalbital and ramelteon both increase sedation. Use Caution/Monitor.
  
  codeine and ramelteon both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• ramipril

  ramipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

• reishi

  aspirin and reishi both increase anticoagulation. Use Caution/Monitor.

• remimazolam

  remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
  
  remimazolam, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

  butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• reteplase

  aspirin, reteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• ribociclib

  ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  rifampin decreases levels of butalbital by increasing metabolism. Use Caution/Monitor.

• risperidone

  codeine and risperidone both increase sedation. Use Caution/Monitor.
  
  butalbital and risperidone both increase sedation. Use Caution/Monitor.
  
  risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ritonavir

  ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rucaparib

  rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

• rivaroxaban

  aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• rivastigmine

  rivastigmine increases toxicity of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

• rolapitant

  rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• sacubitril/valsartan

  sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• salicylates (non-asa)

  aspirin and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

• salmeterol

  butalbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

• salmeterol

  codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• scullcap

  scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salsalate

  aspirin and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salsalate both increase serum potassium. Use Caution/Monitor.

• saquinavir

  butalbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• saw palmetto

  saw palmetto increases toxicity of aspirin by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

• scullcap

  codeine and scullcap both increase sedation. Use Caution/Monitor.
  
  butalbital and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and secobarbital both increase sedation. Use Caution/Monitor.
  
  secobarbital and codeine both increase sedation. Use Caution/Monitor.

• selegiline

  selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
  
  selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

• selumetinib

  aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

• shepherd's purse

  shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sertraline

  sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• Siberian ginseng

  aspirin and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.

• shepherd's purse

  butalbital and shepherd's purse both increase sedation. Use Caution/Monitor.

• sertraline

  sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• sevoflurane

  sevoflurane and codeine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  codeine and shepherd's purse both increase sedation. Use Caution/Monitor.

• sildenafil

  butalbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• silodosin

  aspirin decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• solifenacin

  butalbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• solriamfetol

  caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sorafenib

  butalbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• sotalol

  sotalol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• sparsentan

  aspirin and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.

• stiripentol

  stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

• spironolactone

  spironolactone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.
  
  aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

• sufentanil

  sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• succinylcholine

  aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.

• sufentanil

  codeine and sufentanil both increase sedation. Use Caution/Monitor.
  
  butalbital and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  butalbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.

• sulfamethoxazole

  aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• sulfasalazine

  aspirin and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulfasalazine both increase serum potassium. Use Caution/Monitor.

• sulindac

  aspirin and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulindac both increase serum potassium. Use Caution/Monitor.

• suvorexant

  suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• sunitinib

  butalbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tacrolimus

  butalbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  butalbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tafluprost

  tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tapentadol

  codeine and tapentadol both increase sedation. Use Caution/Monitor.
  
  butalbital and tapentadol both increase sedation. Use Caution/Monitor.
  
  tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• telmisartan

  telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• temazepam

  temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• temazepam

  butalbital and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam and codeine both increase sedation. Use Caution/Monitor.

• temocillin

  temocillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  temocillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• temsirolimus

  butalbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tenecteplase

  aspirin, tenecteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• terazosin

  aspirin decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• terbinafine

  terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbinafine

  butalbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbutaline

  terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• teriflunomide

  teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• thalidomide

  thalidomide increases effects of butalbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

• thioridazine

  thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thiothixene

  thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ticagrelor

  aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.

• thioridazine

  thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and thioridazine both increase sedation. Use Caution/Monitor.

• theophylline

  butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thioridazine

  butalbital and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  codeine and thiothixene both increase sedation. Use Caution/Monitor.
  
  butalbital and thiothixene both increase sedation. Use Caution/Monitor.

• ticarcillin

  ticarcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  ticarcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ticlopidine

  ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• timolol

  timolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• tinidazole

  butalbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tirofiban

  aspirin, tirofiban. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• tipranavir

  butalbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tobramycin inhaled

  tobramycin inhaled and aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolbutamide

  aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolfenamic acid

  aspirin and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

• tolmetin

  aspirin and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolmetin both increase serum potassium. Use Caution/Monitor.

• tolterodine

  butalbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.

• topiramate

  topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• torsemide

  aspirin increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  butalbital and tramadol both increase sedation. Use Caution/Monitor.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.

• trandolapril

  trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.

• tranylcypromine

  tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• travoprost ophthalmic

  travoprost ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  butalbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trazodone

  codeine and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.

• triamcinolone acetonide injectable suspension

  butalbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triamterene

  triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• triazolam

  butalbital and triazolam both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  triazolam and codeine both increase sedation. Use Caution/Monitor.

• triclofos

  triclofos and codeine both increase sedation. Use Caution/Monitor.
  
  triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and triclofos both increase sedation. Use Caution/Monitor.

• trifluoperazine

  butalbital and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trimipramine

  butalbital and trimipramine both increase sedation. Use Caution/Monitor.
  
  codeine and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triprolidine

  triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  triprolidine and butalbital both increase sedation. Use Caution/Monitor.
  
  triprolidine and codeine both increase sedation. Use Caution/Monitor.

• valproic acid

  aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

• xylometazoline

  caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

• valsartan

  valsartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• vardenafil

  butalbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• venlafaxine

  venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• verapamil

  butalbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voclosporin

  voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vorapaxar

  aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.
  
  aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• vortioxetine

  aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

• warfarin

  aspirin increases effects of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Avoid coadministration of chronic high-dose aspirin. Aspirin's antiplatelet properties may increase anticoagulation effect of warfarin. The need for simultaneous use of low-dose aspirin and warfarin is common for patients with cardiovascular disease. .
  
  butalbital will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inducers of these isoenzymes and adjust warfarin dose if needed.

• xylometazoline

  codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  caffeine and yohimbine both decrease sedation. Use Caution/Monitor.

• zanubrutinib

  aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

• yohimbine

  butalbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  butalbital and ziconotide both increase sedation. Use Caution/Monitor.
  
  codeine and ziconotide both increase sedation. Use Caution/Monitor.
  
  ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziprasidone

  butalbital and ziprasidone both increase sedation. Use Caution/Monitor.
  
  codeine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zotepine

  aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  butalbital and zotepine both increase sedation. Use Caution/Monitor.
  
  codeine and zotepine both increase sedation. Use Caution/Monitor.

Minor (267)

• aceclofenac

  aceclofenac will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  acemetacin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acetazolamide

  acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
  
  aspirin will decrease the level or effect of acetazolamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acyclovir

  aspirin will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• adenosine

  caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• alfentanil

  butalbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alendronate

  aspirin, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

• alfuzosin

  butalbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alosetron

  butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aluminum hydroxide

  aluminum hydroxide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• amantadine

  amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amikacin

  aspirin increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• aminohippurate sodium

  aspirin will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• amitriptyline

  butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amobarbital

  amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• amoxapine

  butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amphotericin B deoxycholate

  butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• anamu

  aspirin and anamu both increase anticoagulation. Minor/Significance Unknown.

• anastrozole

  aspirin will decrease the level or effect of anastrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• antipyrine

  butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• armodafinil

  butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ascorbic acid

  aspirin decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.
  
  ascorbic acid increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.
  
  ascorbic acid will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• butabarbital

  butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• asenapine

  butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• balsalazide

  aspirin will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ashwagandha

  ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• bendroflumethiazide

  bendroflumethiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• bismuth subsalicylate

  bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• atazanavir

  butalbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• bosentan

  butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brinzolamide

  brinzolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• bumetanide

  aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

• buprenorphine subdermal implant

  butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• butalbital

  butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• caffeine

  butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• calcium acetate

  caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  calcium carbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).
  
  caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• cefadroxil

  cefadroxil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• calcium citrate

  caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• carbamazepine

  carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cefamandole

  cefamandole will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefepime

  cefepime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefixime

  cefixime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  cefpirome will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefprozil

  cefprozil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftazidime

  ceftazidime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftibuten

  ceftibuten will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cephalexin

  cephalexin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cevimeline

  butalbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ceritinib

  aspirin will decrease the level or effect of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• chloramphenicol

  chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpromazine

  butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• chlorpropamide

  aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chlorthalidone

  chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• choline magnesium trisalicylate

  aspirin will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chromium

  aspirin increases levels of chromium by unspecified interaction mechanism. Minor/Significance Unknown.

• cigarette smoking

  cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cimetidine

  cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• clarithromycin

  butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clotrimazole

  clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• clomipramine

  butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clotrimazole

  butalbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cocaine topical

  butalbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• cortisone

  cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• creatine

  creatine, aspirin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

• cyanocobalamin

  aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclopenthiazide

  cyclopenthiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  aspirin will decrease the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• danshen

  aspirin and danshen both increase anticoagulation. Minor/Significance Unknown.

• dapsone

  butalbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• deflazacort

  deflazacort decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• desipramine

  butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• devil's claw

  aspirin and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexamethasone

  dexamethasone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• dextroamphetamine

  dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• diclofenac

  butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• disopyramide

  butalbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diflunisal

  aspirin will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diltiazem

  diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• docetaxel

  butalbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• donepezil

  butalbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dosulepin

  butalbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxepin

  butalbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• dutasteride

  butalbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• efavirenz

  butalbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eplerenone

  butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  aspirin decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• erythromycin base

  butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• ethanol

  ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

• erythromycin ethylsuccinate

  butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• ethosuximide

  ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• etodolac

  aspirin will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• eucalyptus

  butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• fenbufen

  aspirin will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fluconazole

  fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• fenoprofen

  aspirin will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• feverfew

  aspirin decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• finasteride

  butalbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• fluoxetine

  fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• fluconazole

  butalbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• flurbiprofen

  aspirin will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• folic acid

  aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• frovatriptan

  butalbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• furosemide

  aspirin decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• galantamine

  butalbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ganciclovir

  aspirin will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• gentamicin

  aspirin increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• glimepiride

  aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glipizide

  aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glyburide

  aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• grapefruit

  grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• griseofulvin

  butalbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• guarana

  guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• haloperidol

  haloperidol, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

• hydrochlorothiazide

  hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocortisone

  hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• ibuprofen

  butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  butalbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• imidapril

  aspirin decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• imatinib

  imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
  
  butalbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imipramine

  butalbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• indapamide

  indapamide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  aspirin will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• itraconazole

  itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ketoconazole

  ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ketoprofen

  aspirin will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  aspirin will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  aspirin will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• L-methylfolate

  aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• larotrectinib

  aspirin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levoketoconazole

  levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  aspirin will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lidocaine

  lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• mexiletine

  mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• isocarboxazid

  isocarboxazid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• isradipine

  butalbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ketoconazole

  butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• lansoprazole

  butalbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• levoketoconazole

  butalbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• levothyroxine

  butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• linezolid

  linezolid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• liothyronine

  butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lofepramine

  butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• lornoxicam

  aspirin will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  butalbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• maprotiline

  butalbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• maraviroc

  maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• meclofenamate

  aspirin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  aspirin will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  aspirin will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• mesalamine

  aspirin will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methazolamide

  methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methsuximide

  methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyclothiazide

  methyclothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methylprednisolone

  methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• metolazone

  metolazone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miconazole vaginal

  butalbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• montelukast

  butalbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• peginterferon alfa 2a

  peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• nabumetone

  aspirin will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• naproxen

  aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• neomycin PO

  aspirin increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• nettle

  nettle increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nifedipine

  butalbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• nimodipine

  butalbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nitrendipine

  butalbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• noni juice

  aspirin and noni juice both increase serum potassium. Minor/Significance Unknown.

• nortriptyline

  butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• ofloxacin

  ofloxacin, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• oxaprozin

  aspirin will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxybutynin

  butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel

  butalbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  butalbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• parecoxib

  parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  aspirin increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• pentobarbital

  pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perphenazine

  perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• penicillin VK

  penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

• pentazocine

  aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

• phenelzine

  phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• phenobarbital

  phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pimozide

  butalbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pioglitazone

  butalbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pipemidic acid

  pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• piperacillin

  piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

• piroxicam

  aspirin will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• posaconazole

  butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• prednisolone

  prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• primidone

  primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• prednisone

  prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• propafenone

  propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• protriptyline

  butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• quinacrine

  quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• quinine

  butalbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rabeprazole

  butalbital will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ranolazine

  ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rifampin

  rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• riluzole

  butalbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• rose hips

  aspirin decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.
  
  rose hips will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.
  
  rose hips increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

• sage

  sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  codeine and sage both increase sedation. Minor/Significance Unknown.
  
  butalbital and sage both increase sedation. Minor/Significance Unknown.

• salicylates (non-asa)

  aspirin will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• secobarbital

  secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• salsalate

  aspirin will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• saxagliptin

  butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sertraline

  sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• selegiline transdermal

  selegiline transdermal increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• Siberian ginseng

  Siberian ginseng increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• smoking

  smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• sodium bicarbonate

  sodium bicarbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• sodium citrate/citric acid

  sodium citrate/citric acid, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• stiripentol

  aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• streptomycin

  aspirin increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• sufentanil

  butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sulfadiazine

  aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sulfasalazine

  aspirin will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  aspirin will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tamoxifen

  butalbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• teniposide

  aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

• thiamine

  caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
  
  thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown.

• thyroid desiccated

  butalbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

• tiludronate

  aspirin decreases levels of tiludronate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• tipranavir

  tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tibolone

  butalbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• tobacco use

  tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tobramycin

  aspirin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• tolazamide

  aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolbutamide

  butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolfenamic acid

  aspirin will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• topiramate

  butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• tolmetin

  aspirin will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tranylcypromine

  tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• trazodone

  butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• triamterene

  triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• trimipramine

  butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• valganciclovir

  aspirin will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• vancomycin

  aspirin increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• venlafaxine

  venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• verapamil

  verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.
  
  verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• vinblastine

  butalbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• voriconazole

  voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• vincristine

  butalbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  butalbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  butalbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• voriconazole

  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• willow bark

  aspirin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  willow bark increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

• yerba mate

  yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• zafirlukast

  aspirin increases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

• zaleplon

  butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziconotide

  ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• zileuton

  zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ziprasidone

  butalbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abciximab

  Monitor Closely (1)aspirin, abciximab. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• abemaciclib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• abiraterone

  Monitor Closely (2)abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
  
  butalbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• abrocitinib

  Contraindicated (1)abrocitinib and aspirin both increase anticoagulation. Contraindicated. Antiplatelet drugs, except for low-dose aspirin (=81 mg qDay), during the first 3 months of treatment are contraindicated.

• acalabrutinib

  Monitor Closely (2)acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.
  
  butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• acebutolol

  Monitor Closely (3)aspirin decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  acebutolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• aceclofenac

  Monitor Closely (2)aceclofenac and aspirin both increase anticoagulation. Use Caution/Monitor.
  
  aceclofenac and aspirin both increase serum potassium. Use Caution/Monitor.Minor (1)aceclofenac will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (2)acemetacin and aspirin both increase anticoagulation. Use Caution/Monitor.
  
  acemetacin and aspirin both increase serum potassium. Use Caution/Monitor.Minor (1)acemetacin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acetazolamide

  Monitor Closely (2)acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).
  
  acetazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.Minor (2)acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
  
  aspirin will decrease the level or effect of acetazolamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acrivastine

  Monitor Closely (1)acrivastine and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• acyclovir

  Minor (1)aspirin will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• adenosine

  Minor (1)caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• agrimony

  Monitor Closely (1)aspirin and agrimony both increase anticoagulation. Use Caution/Monitor.

• albuterol

  Monitor Closely (4)butalbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and caffeine both decrease sedation. Use Caution/Monitor.

• alendronate

  Minor (1)aspirin, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

• alfalfa

  Monitor Closely (1)aspirin and alfalfa both increase anticoagulation. Use Caution/Monitor.

• alfentanil

  Monitor Closely (3)alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  alfentanil and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and alfentanil both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

  Monitor Closely (1)aspirin decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.Minor (1)butalbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aliskiren

  Monitor Closely (1)aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

• almotriptan

  Monitor Closely (1)butalbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alosetron

  Serious - Use Alternative (1)butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.Minor (2)butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alpelisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

• alprazolam

  Monitor Closely (4)alprazolam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and alprazolam both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alteplase

  Monitor Closely (1)aspirin, alteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• aluminum hydroxide

  Minor (1)aluminum hydroxide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• alvimopan

  Contraindicated (1)alvimopan, codeine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• amantadine

  Minor (1)amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  Minor (1)American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amikacin

  Minor (1)aspirin increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• amiloride

  Monitor Closely (1)amiloride and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• aminohippurate sodium

  Minor (1)aspirin will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• amiodarone

  Monitor Closely (2)butalbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• amisulpride

  Monitor Closely (1)amisulpride and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.

• amitriptyline

  Monitor Closely (5)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amlodipine

  Monitor Closely (1)butalbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amobarbital

  Monitor Closely (3)amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amobarbital and butalbital both increase sedation. Use Caution/Monitor.
  
  amobarbital and codeine both increase sedation. Use Caution/Monitor.Minor (1)amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (3)amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and amoxapine both increase sedation. Use Caution/Monitor.
  
  codeine and amoxapine both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxicillin

  Monitor Closely (2)amoxicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  amoxicillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• amphotericin B deoxycholate

  Minor (1)butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ampicillin

  Monitor Closely (1)ampicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• anagrelide

  Monitor Closely (2)aspirin, anagrelide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.
  
  anagrelide, aspirin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.

• anamu

  Minor (1)aspirin and anamu both increase anticoagulation. Minor/Significance Unknown.

• anastrozole

  Minor (1)aspirin will decrease the level or effect of anastrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• antipyrine

  Minor (1)butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Monitor Closely (2)antithrombin alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin alfa. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)butalbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

• antithrombin III

  Monitor Closely (2)antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin III. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)butalbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

• apixaban

  Monitor Closely (1)aspirin and apixaban both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspiriin. Avoid coadministration with chronic use of higher dose aspirin. In 1 trial (APPRAISE-2), therapy was terminated because of significantly increased bleeding when apixaban was administered with dual antiplatelet therapy (eg, aspirin plus clopidogrel) compared with single antiplatelet treatment

• apomorphine

  Monitor Closely (2)butalbital and apomorphine both increase sedation. Use Caution/Monitor.
  
  codeine and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

  Monitor Closely (1)butalbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (4)butalbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and caffeine both decrease sedation. Use Caution/Monitor.

• argatroban

  Monitor Closely (2)aspirin, argatroban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  argatroban and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

• aripiprazole

  Monitor Closely (4)aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and aripiprazole both increase sedation. Use Caution/Monitor.
  
  codeine and aripiprazole both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• armodafinil

  Monitor Closely (3)butalbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil and caffeine both decrease sedation. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  Monitor Closely (2)artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ascorbic acid

  Minor (4)aspirin decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.
  
  ascorbic acid increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.
  
  ascorbic acid will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• asenapine

  Monitor Closely (2)aspirin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  asenapine and butalbital both increase sedation. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• ashwagandha

  Minor (1)ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atazanavir

  Minor (1)butalbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atenolol

  Monitor Closely (3)atenolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• atogepant

  Monitor Closely (1)butalbital will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

• atorvastatin

  Monitor Closely (1)butalbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avanafil

  Monitor Closely (1)butalbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness

• avapritinib

  Monitor Closely (1)avapritinib and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• azelastine

  Monitor Closely (3)azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  azelastine and butalbital both increase sedation. Use Caution/Monitor.
  
  azelastine and codeine both increase sedation. Use Caution/Monitor.

• azficel-T

  Monitor Closely (1)azficel-T, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking aspirin may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of aspirin is not recommended. .

• azilsartan

  Monitor Closely (2)aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

  Monitor Closely (2)baclofen and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and baclofen both increase sedation. Use Caution/Monitor.

• balsalazide

  Minor (1)aspirin will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• bazedoxifene/conjugated estrogens

  Monitor Closely (1)butalbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (3)butalbital and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belumosudil

  Monitor Closely (1)butalbital will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.

• bemiparin

  Monitor Closely (1)bemiparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

• benazepril

  Monitor Closely (2)butalbital increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor.
  
  benazepril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• bendroflumethiazide

  Monitor Closely (1)aspirin increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)bendroflumethiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• benperidol

  Monitor Closely (3)butalbital and benperidol both increase sedation. Use Caution/Monitor.
  
  codeine and benperidol both increase sedation. Use Caution/Monitor.
  
  benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (4)benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• benzphetamine

  Monitor Closely (3)butalbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.

• betaxolol

  Monitor Closely (3)betaxolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• betrixaban

  Monitor Closely (1)aspirin, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bimatoprost

  Monitor Closely (1)bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• bismuth subsalicylate

  Minor (1)bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

  Monitor Closely (3)bisoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bivalirudin

  Monitor Closely (2)bivalirudin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, bivalirudin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)butalbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

• bortezomib

  Monitor Closely (1)butalbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosentan

  Minor (2)butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexanolone

  Monitor Closely (2)brexanolone, butalbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
  
  brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)brexpiprazole and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brigatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

• brimonidine

  Monitor Closely (1)brimonidine and butalbital both increase sedation. Use Caution/Monitor.Minor (2)brimonidine increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
  
  brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.Serious - Use Alternative (1)brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brinzolamide

  Monitor Closely (1)brinzolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.Minor (1)brinzolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• brivaracetam

  Monitor Closely (2)brivaracetam and codeine both increase sedation. Use Caution/Monitor.
  
  brivaracetam and butalbital both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (3)brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  brompheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  brompheniramine and codeine both increase sedation. Use Caution/Monitor.

• budesonide

  Monitor Closely (1)butalbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bumetanide

  Monitor Closely (2)aspirin decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  aspirin increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

• buprenorphine

  Monitor Closely (2)butalbital and buprenorphine both increase sedation. Use Caution/Monitor.
  
  buprenorphine and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  Monitor Closely (3)butalbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine subdermal implant

  Serious - Use Alternative (2)buprenorphine subdermal implant and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateMinor (1)butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• buprenorphine transdermal

  Serious - Use Alternative (2)buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (3)butalbital increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  butalbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.Serious - Use Alternative (2)buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine, long-acting injection and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (2)butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .
  
  bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• buspirone

  Monitor Closely (1)butalbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  Monitor Closely (3)butabarbital and butalbital both increase sedation. Use Caution/Monitor.
  
  butabarbital and codeine both increase sedation. Use Caution/Monitor.
  
  butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butalbital

  Monitor Closely (2)butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butorphanol

  Monitor Closely (3)butorphanol and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and butorphanol both increase sedation. Use Caution/Monitor.
  
  butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• caffeine

  Monitor Closely (2)butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• calcium acetate

  Minor (1)caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  Minor (2)calcium carbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).
  
  caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  Minor (1)caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  Minor (1)caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  Minor (1)caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (2)codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  butalbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• candesartan

  Monitor Closely (3)candesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• cannabidiol

  Monitor Closely (1)butalbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

• capivasertib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.

• caplacizumab

  Serious - Use Alternative (1)caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• captopril

  Monitor Closely (2)butalbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.
  
  captopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• carbamazepine

  Monitor Closely (1)butalbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• carbenoxolone

  Monitor Closely (1)aspirin increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

  Monitor Closely (3)carbinoxamine and butalbital both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (2)butalbital and carisoprodol both increase sedation. Use Caution/Monitor.
  
  carisoprodol and codeine both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (4)butalbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  carvedilol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefepime

  Minor (1)cefepime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefixime

  Minor (1)cefixime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefprozil

  Minor (1)cefprozil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftazidime

  Minor (1)ceftazidime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftibuten

  Minor (1)ceftibuten will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (3)aspirin and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  aspirin and celecoxib both increase anticoagulation. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (3)celiprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• cenobamate

  Monitor Closely (2)cenobamate, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.

• cephalexin

  Minor (1)cephalexin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceritinib

  Minor (1)aspirin will decrease the level or effect of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cevimeline

  Minor (1)butalbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• chloral hydrate

  Monitor Closely (3)chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chloral hydrate both increase sedation. Use Caution/Monitor.
  
  chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloramphenicol

  Minor (2)chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlordiazepoxide

  Monitor Closely (3)chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• chlorothiazide

  Monitor Closely (1)aspirin increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (3)chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (4)chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
  
  butalbital and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• chlorpropamide

  Monitor Closely (1)aspirin increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (2)aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chlorthalidone

  Monitor Closely (1)aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (2)chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• choline magnesium trisalicylate

  Monitor Closely (2)aspirin and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chromium

  Minor (1)aspirin increases levels of chromium by unspecified interaction mechanism. Minor/Significance Unknown.

• cigarette smoking

  Minor (1)cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cilostazol

  Monitor Closely (2)aspirin, cilostazol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  butalbital will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (2)cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• cinacalcet

  Monitor Closely (2)cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnamon

  Monitor Closely (1)aspirin and cinnamon both increase anticoagulation. Use Caution/Monitor.

• cinnarizine

  Monitor Closely (3)cinnarizine and butalbital both increase sedation. Use Caution/Monitor.
  
  cinnarizine and codeine both increase sedation. Use Caution/Monitor.
  
  cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ciprofloxacin

  Monitor Closely (2)aspirin decreases levels of ciprofloxacin by Other (see comment). Use Caution/Monitor. Comment: Buffered aspirin may decrease absorption of quinolones. Consider administering 2 hr before or 6 hr after, buffered aspirin administration.
  
  ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

• citalopram

  Monitor Closely (1)citalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clarithromycin

  Minor (2)butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clemastine

  Monitor Closely (3)clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clemastine and butalbital both increase sedation. Use Caution/Monitor.
  
  clemastine and codeine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (2)codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clomipramine

  Monitor Closely (7)butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  clomipramine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.
  
  butalbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and clomipramine both increase sedation. Use Caution/Monitor.
  
  codeine and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clonazepam

  Monitor Closely (3)butalbital and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clonazepam and codeine both increase sedation. Use Caution/Monitor.

• clonidine

  Serious - Use Alternative (1)clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clopidogrel

  Monitor Closely (2)butalbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel
  
  aspirin, clopidogrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• clorazepate

  Monitor Closely (3)clorazepate and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and clorazepate both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clotrimazole

  Minor (2)clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• clozapine

  Monitor Closely (6)butalbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and clozapine both increase sedation. Use Caution/Monitor.
  
  codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cocaine topical

  Monitor Closely (1)cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)butalbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• codeine

  Monitor Closely (2)butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• colchicine

  Monitor Closely (1)butalbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• collagenase clostridium histolyticum

  Monitor Closely (1)aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

• conivaptan

  Monitor Closely (1)butalbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  Monitor Closely (1)butalbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (1)butalbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• copanlisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cordyceps

  Monitor Closely (1)aspirin and cordyceps both increase anticoagulation. Use Caution/Monitor.

• cortisone

  Monitor Closely (2)aspirin, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.
  
  butalbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• creatine

  Minor (1)creatine, aspirin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

• cyanocobalamin

  Minor (1)aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (3)cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  cyclizine and butalbital both increase sedation. Use Caution/Monitor.
  
  cyclizine and codeine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)butalbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.

• cyclopenthiazide

  Monitor Closely (1)aspirin increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)cyclopenthiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  Minor (1)aspirin will decrease the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)butalbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (3)cyproheptadine and butalbital both increase sedation. Use Caution/Monitor.
  
  cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
  
  cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dabigatran

  Monitor Closely (1)dabigatran and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin

• dacomitinib

  Serious - Use Alternative (1)dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dalteparin

  Monitor Closely (2)aspirin, dalteparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  dalteparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.

• danshen

  Minor (1)aspirin and danshen both increase anticoagulation. Minor/Significance Unknown.

• dantrolene

  Monitor Closely (2)dantrolene and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone

  Minor (1)butalbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• daridorexant

  Monitor Closely (2)butalbital and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  codeine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. Serious - Use Alternative (1)butalbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  Monitor Closely (2)darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (1)butalbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dasatinib

  Monitor Closely (1)butalbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  Monitor Closely (2)deferasirox, aspirin. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.
  
  deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• defibrotide

  Monitor Closely (1)defibrotide increases effects of aspirin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  Monitor Closely (1)aspirin, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Serious - Use Alternative (1)butalbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.Minor (1)deflazacort decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• desflurane

  Monitor Closely (1)desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  Monitor Closely (4)butalbital and desipramine both increase sedation. Use Caution/Monitor.
  
  codeine and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• desirudin

  Monitor Closely (1)aspirin, desirudin. Either increases levels of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  Monitor Closely (2)butalbital and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• devil's claw

  Minor (1)aspirin and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (2)butalbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)dexamethasone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• dexchlorpheniramine

  Monitor Closely (3)dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexchlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (3)butalbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (3)dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (3)butalbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (3)butalbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.Minor (1)dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (3)butalbital and dextromoramide both increase sedation. Use Caution/Monitor.
  
  codeine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  Monitor Closely (3)butalbital and diamorphine both increase sedation. Use Caution/Monitor.
  
  codeine and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diazepam

  Monitor Closely (3)diazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (2)butalbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
  
  diazepam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.Serious - Use Alternative (1)diazepam intranasal, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• dichlorphenamide

  Contraindicated (1)dichlorphenamide increases levels of aspirin by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

• diclofenac

  Monitor Closely (2)aspirin and diclofenac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diclofenac both increase serum potassium. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  Minor (1)diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• dicloxacillin

  Monitor Closely (1)dicloxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (3)butalbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (2)difelikefalin and codeine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and butalbital both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (3)difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diflunisal

  Monitor Closely (2)aspirin and diflunisal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diflunisal both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (1)aspirin and digoxin both increase serum potassium. Use Caution/Monitor.

• dihydroergotamine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)butalbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diltiazem

  Monitor Closely (1)butalbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• dimenhydrinate

  Monitor Closely (3)dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dimenhydrinate and butalbital both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (4)diphenhydramine and butalbital both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (3)butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  Monitor Closely (3)butalbital and dipipanone both increase sedation. Use Caution/Monitor.
  
  codeine and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipyridamole

  Monitor Closely (1)aspirin, dipyridamole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (2)caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
  
  butalbital decreases levels of dipyridamole by increasing metabolism. Contraindicated.

• disopyramide

  Minor (1)butalbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (4)butalbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dobutamine and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• docetaxel

  Minor (1)butalbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• donepezil

  Minor (1)butalbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dong quai

  Monitor Closely (1)aspirin and dong quai both increase anticoagulation. Use Caution/Monitor.

• dopamine

  Monitor Closely (3)butalbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dopamine both decrease sedation. Use Caution/Monitor.

• dopexamine

  Monitor Closely (4)aspirin increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

• doravirine

  Contraindicated (1)butalbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• dosulepin

  Monitor Closely (2)butalbital and dosulepin both increase sedation. Use Caution/Monitor.
  
  codeine and dosulepin both increase sedation. Use Caution/Monitor.Minor (1)butalbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxazosin

  Monitor Closely (1)aspirin decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• doxepin

  Monitor Closely (3)butalbital and doxepin both increase sedation. Use Caution/Monitor.
  
  codeine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxycycline

  Monitor Closely (1)butalbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

• doxylamine

  Monitor Closely (2)butalbital and doxylamine both increase sedation. Use Caution/Monitor.
  
  doxylamine and codeine both increase sedation. Use Caution/Monitor.

• dronabinol

  Monitor Closely (1)butalbital will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Monitor Closely (1)dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)butalbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• droperidol

  Monitor Closely (3)butalbital and droperidol both increase sedation. Use Caution/Monitor.
  
  codeine and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• drospirenone

  Monitor Closely (1)drospirenone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• droxidopa

  Monitor Closely (1)caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  Monitor Closely (2)duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• dutasteride

  Minor (1)butalbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• duvelisib

  Serious - Use Alternative (1)butalbital will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• edoxaban

  Monitor Closely (1)edoxaban, aspirin. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• efavirenz

  Minor (1)butalbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elacestrant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)butalbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eletriptan

  Monitor Closely (1)butalbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eltrombopag

  Monitor Closely (2)butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• eluxadoline

  Serious - Use Alternative (1)codeine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enalapril

  Monitor Closely (1)enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• enoxaparin

  Monitor Closely (2)enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI
  
  aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)butalbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (4)aspirin increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (4)epinephrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine inhaled

  Monitor Closely (1)caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (4)butalbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• eplerenone

  Minor (2)butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  aspirin decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• epoprostenol

  Monitor Closely (1)aspirin and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• eprosartan

  Monitor Closely (3)aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• eptifibatide

  Monitor Closely (1)aspirin, eptifibatide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• erdafitinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ergotamine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erlotinib

  Monitor Closely (1)butalbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• escitalopram

  Monitor Closely (2)butalbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  escitalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  Monitor Closely (3)esketamine intranasal, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
  
  esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
  
  esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

• esmolol

  Monitor Closely (3)aspirin decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  esmolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• estazolam

  Monitor Closely (3)estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and estazolam both increase sedation. Use Caution/Monitor.
  
  estazolam and codeine both increase sedation. Use Caution/Monitor.

• estradiol

  Monitor Closely (1)butalbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  Monitor Closely (1)butalbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)butalbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)butalbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)aspirin increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

  Monitor Closely (3)ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and ethanol both increase sedation. Use Caution/Monitor.
  
  codeine and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• ethosuximide

  Minor (1)ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• ethotoin

  Monitor Closely (1)butalbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etodolac

  Monitor Closely (2)aspirin and etodolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and etodolac both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• etomidate

  Monitor Closely (2)etomidate and butalbital both increase sedation. Use Caution/Monitor.
  
  etomidate and codeine both increase sedation. Use Caution/Monitor.

• etonogestrel

  Monitor Closely (1)butalbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  Monitor Closely (3)butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (4)butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  codeine and eucalyptus both increase sedation. Minor/Significance Unknown.

• everolimus

  Serious - Use Alternative (1)butalbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.Serious - Use Alternative (1)butalbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• felodipine

  Monitor Closely (1)butalbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenbufen

  Monitor Closely (2)aspirin and fenbufen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenbufen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenfluramine

  Monitor Closely (3)butalbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.

• fennel

  Monitor Closely (1)aspirin and fennel both increase anticoagulation. Use Caution/Monitor.

• fenoprofen

  Monitor Closely (2)aspirin and fenoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Serious - Use Alternative (4)fentanyl and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Serious - Use Alternative (4)fentanyl intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl intranasal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (2)fentanyl iontophoretic transdermal system and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl iontophoretic transdermal system and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  Serious - Use Alternative (4)fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  Serious - Use Alternative (2)fentanyl transmucosal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transmucosal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fesoterodine

  Monitor Closely (1)butalbital will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• feverfew

  Monitor Closely (1)aspirin and feverfew both increase anticoagulation. Use Caution/Monitor.Minor (1)aspirin decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• fezolinetant

  Contraindicated (1)caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• finasteride

  Minor (1)butalbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• finerenone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fish oil

  Monitor Closely (1)fish oil, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• fish oil triglycerides

  Monitor Closely (1)fish oil triglycerides will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flibanserin

  Monitor Closely (2)codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  butalbital and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Minor (2)butalbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (2)butalbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)fludrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (2)fluoxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphineMinor (1)fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• fluphenazine

  Monitor Closely (3)fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and fluphenazine both increase sedation. Use Caution/Monitor.
  
  codeine and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (3)butalbital and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam and codeine both increase sedation. Use Caution/Monitor.
  
  flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• flurbiprofen

  Monitor Closely (2)aspirin and flurbiprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and flurbiprofen both increase serum potassium. Use Caution/Monitor.Minor (2)aspirin will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (2)fluvoxamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding SSRIs inhib. serotonin uptake by platelets.
  
  fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• folic acid

  Minor (1)aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fondaparinux

  Monitor Closely (1)fondaparinux and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (4)butalbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  formoterol and caffeine both decrease sedation. Use Caution/Monitor.

• forskolin

  Monitor Closely (1)aspirin and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosamprenavir

  Monitor Closely (1)butalbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  Monitor Closely (1)butalbital will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)fosinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• fosphenytoin

  Monitor Closely (1)butalbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fostamatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fostemsavir

  Contraindicated (1)butalbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• frovatriptan

  Minor (1)butalbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• fruquintinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.

• furosemide

  Monitor Closely (1)aspirin increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• gabapentin

  Monitor Closely (2)gabapentin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  gabapentin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (2)gabapentin enacarbil, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  gabapentin enacarbil, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  Minor (1)butalbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ganaxolone

  Monitor Closely (2)butalbital and ganaxolone both increase sedation. Use Caution/Monitor.
  
  codeine and ganaxolone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• ganciclovir

  Minor (1)aspirin will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• garlic

  Monitor Closely (1)aspirin and garlic both increase anticoagulation. Use Caution/Monitor.

• gentamicin

  Monitor Closely (1)aspirin increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• ginger

  Monitor Closely (1)aspirin and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  Monitor Closely (1)aspirin and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (2)givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
  
  givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• glasdegib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glecaprevir/pibrentasvir

  Monitor Closely (1)butalbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

• glimepiride

  Monitor Closely (1)aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glipizide

  Monitor Closely (1)aspirin increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glyburide

  Monitor Closely (1)aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• gotu kola

  Monitor Closely (1)gotu kola increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• grapefruit

  Minor (1)grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• green tea

  Monitor Closely (2)green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.
  
  green tea increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.

• griseofulvin

  Monitor Closely (1)griseofulvin decreases levels of aspirin by unknown mechanism. Use Caution/Monitor.Minor (1)butalbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)butalbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• guarana

  Minor (1)guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• guselkumab

  Monitor Closely (1)guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  Monitor Closely (4)haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and haloperidol both increase sedation. Use Caution/Monitor.
  
  codeine and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)haloperidol, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

• hawthorn

  Monitor Closely (1)hawthorn increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hemin

  Monitor Closely (1)butalbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• heparin

  Monitor Closely (2)aspirin, heparin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  heparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

• hops

  Monitor Closely (1)hops increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• horse chestnut seed

  Monitor Closely (1)aspirin and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

• hyaluronidase

  Monitor Closely (1)aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  Monitor Closely (1)aspirin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  Monitor Closely (1)aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocodone

  Serious - Use Alternative (2)hydrocodone, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• hydrocortisone

  Monitor Closely (2)butalbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• hydromorphone

  Monitor Closely (3)butalbital and hydromorphone both increase sedation. Use Caution/Monitor.
  
  codeine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

  Monitor Closely (1)butalbital will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (3)hydroxyzine and butalbital both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ibrutinib

  Monitor Closely (1)ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen

  Monitor Closely (2)aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.Serious - Use Alternative (2)ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.
  
  ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

• ibuprofen IV

  Monitor Closely (3)aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.
  
  aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.Minor (1)butalbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.Serious - Use Alternative (2)ibuprofen IV decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.
  
  ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

• icosapent

  Monitor Closely (1)icosapent, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time. Periodically monitor if coadministered with other drugs that affect bleeding.

• ifosfamide

  Monitor Closely (2)butalbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  butalbital increases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• iloperidone

  Monitor Closely (4)butalbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and iloperidone both increase sedation. Use Caution/Monitor.
  
  codeine and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• imatinib

  Monitor Closely (1)imatinib, aspirin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.Minor (3)butalbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
  
  imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imidapril

  Minor (1)aspirin decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• imipramine

  Monitor Closely (7)butalbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and imipramine both increase sedation. Use Caution/Monitor.
  
  codeine and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)butalbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• indapamide

  Monitor Closely (1)aspirin increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)indapamide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indinavir

  Monitor Closely (1)butalbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indomethacin

  Monitor Closely (2)aspirin and indomethacin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and indomethacin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• infigratinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin aspart protamine/insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec

  Monitor Closely (1)aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  Monitor Closely (1)aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

• insulin detemir

  Monitor Closely (1)aspirin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glargine

  Monitor Closely (1)aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glulisine

  Monitor Closely (1)aspirin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  Monitor Closely (1)aspirin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin isophane human/insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro protamine/insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin NPH

  Monitor Closely (1)aspirin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• iobenguane I 131

  Serious - Use Alternative (1)caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• irbesartan

  Monitor Closely (3)irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• isavuconazonium sulfate

  Contraindicated (1)butalbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isocarboxazid

  Contraindicated (1)isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (2)isocarboxazid, butalbital. Other (see comment). Contraindicated. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.
  
  isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.Minor (1)isocarboxazid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• isoniazid

  Monitor Closely (1)isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• isoproterenol

  Monitor Closely (4)butalbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• isradipine

  Minor (1)butalbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• istradefylline

  Serious - Use Alternative (1)butalbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  Minor (1)itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ivosidenib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ixabepilone

  Monitor Closely (1)butalbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• kava

  Monitor Closely (1)kava increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (2)ketamine and butalbital both increase sedation. Use Caution/Monitor.
  
  ketamine and codeine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (1)ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (3)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ketoprofen

  Monitor Closely (2)aspirin and ketoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)aspirin and ketorolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)aspirin, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)aspirin will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)aspirin and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)aspirin, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)aspirin will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketotifen, ophthalmic

  Monitor Closely (3)butalbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• L-methylfolate

  Minor (1)aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• labetalol

  Monitor Closely (3)aspirin decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  labetalol and aspirin both increase serum potassium. Use Caution/Monitor.

• lansoprazole

  Minor (1)butalbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• lapatinib

  Monitor Closely (1)butalbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• larotrectinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.Minor (1)aspirin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor Closely (2)lasmiditan, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  lasmiditan, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprost

  Monitor Closely (1)latanoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• latanoprostene bunod ophthalmic

  Monitor Closely (1)latanoprostene bunod ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lefamulin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  Monitor Closely (1)lemborexant, codeine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.Serious - Use Alternative (2)butalbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  lemborexant, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

• lenacapavir

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lesinurad

  Serious - Use Alternative (1)aspirin decreases effects of lesinurad by unspecified interaction mechanism. Avoid or Use Alternate Drug. Aspirin at doses >325 mg/day may decrease lesinurad efficacy. Aspirin doses 325 mg/day or less (ie, for cardiovascular event prophylaxis) does not decrease lesinurad efficacy and can be coadministered.

• letermovir

  Monitor Closely (2)letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (4)aspirin increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• levamlodipine

  Monitor Closely (1)butalbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levoketoconazole

  Monitor Closely (1)levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (4)levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  aspirin will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)butalbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• levorphanol

  Monitor Closely (3)levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and levorphanol both increase sedation. Use Caution/Monitor.
  
  codeine and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.Minor (1)butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• lidocaine

  Monitor Closely (1)butalbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (1)lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• linezolid

  Contraindicated (1)linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)linezolid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.Serious - Use Alternative (1)linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• liothyronine

  Minor (1)butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lisdexamfetamine

  Monitor Closely (3)butalbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.

• lisinopril

  Monitor Closely (1)lisinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lithium

  Monitor Closely (1)aspirin increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

• lofepramine

  Monitor Closely (3)butalbital and lofepramine both increase sedation. Use Caution/Monitor.
  
  codeine and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• lofexidine

  Monitor Closely (3)butalbital and lofexidine both increase sedation. Use Caution/Monitor.
  
  codeine and lofexidine both increase sedation. Use Caution/Monitor.
  
  lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lonafarnib

  Contraindicated (1)butalbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lopinavir

  Monitor Closely (2)lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  Monitor Closely (3)butalbital and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  loprazolam and codeine both increase sedation. Use Caution/Monitor.

• loratadine

  Monitor Closely (1)butalbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lorazepam

  Monitor Closely (3)butalbital and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  lorazepam and codeine both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• lorlatinib

  Contraindicated (1)butalbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• lormetazepam

  Monitor Closely (3)lormetazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and lormetazepam both increase sedation. Use Caution/Monitor.
  
  lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lornoxicam

  Monitor Closely (2)aspirin and lornoxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and lornoxicam both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (3)aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  losartan and aspirin both increase serum potassium. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lovastatin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• loxapine

  Monitor Closely (3)butalbital and loxapine both increase sedation. Use Caution/Monitor.
  
  codeine and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  butalbital and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumateperone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumefantrine

  Monitor Closely (2)butalbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (2)lurasidone, butalbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• lurbinectedin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  Serious - Use Alternative (2)butalbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.
  
  aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

• maprotiline

  Monitor Closely (3)maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and maprotiline both increase sedation. Use Caution/Monitor.
  
  codeine and maprotiline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• maraviroc

  Monitor Closely (1)butalbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (3)butalbital and marijuana both increase sedation. Use Caution/Monitor.
  
  codeine and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• mavacamten

  Contraindicated (1)butalbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• measles, mumps, rubella and varicella vaccine, live

  Serious - Use Alternative (1)aspirin, measles, mumps, rubella and varicella vaccine, live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• meclofenamate

  Monitor Closely (2)aspirin and meclofenamate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meclofenamate both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)aspirin and mefenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and mefenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• melatonin

  Monitor Closely (4)melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.
  
  melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and melatonin both increase sedation. Use Caution/Monitor.
  
  codeine and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  Monitor Closely (2)aspirin and meloxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meloxicam both increase serum potassium. Use Caution/Monitor.Minor (2)aspirin will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• meperidine

  Monitor Closely (3)butalbital and meperidine both increase sedation. Use Caution/Monitor.
  
  codeine and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meprobamate

  Monitor Closely (3)meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and meprobamate both increase sedation. Use Caution/Monitor.
  
  codeine and meprobamate both increase sedation. Use Caution/Monitor.

• mesalamine

  Monitor Closely (1)mesalamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.Minor (1)aspirin will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mestranol

  Monitor Closely (1)butalbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)butalbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

• metaproterenol

  Monitor Closely (4)aspirin increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (2)butalbital and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and codeine both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (4)butalbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and methadone both increase sedation. Use Caution/Monitor.
  
  codeine and methadone both increase sedation. Use Caution/Monitor.
  
  methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (3)butalbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.

• methazolamide

  Monitor Closely (1)methazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.Minor (1)methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methocarbamol

  Monitor Closely (2)butalbital and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and codeine both increase sedation. Use Caution/Monitor.

• methotrexate

  Monitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.Serious - Use Alternative (1)aspirin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.

• methoxyflurane

  Serious - Use Alternative (1)butalbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

• methsuximide

  Minor (1)methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyclothiazide

  Monitor Closely (1)aspirin increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)methyclothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methylene blue

  Serious - Use Alternative (2)methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
  
  methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• methylenedioxymethamphetamine

  Monitor Closely (3)butalbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.

• methylphenidate

  Monitor Closely (1)caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• methylprednisolone

  Monitor Closely (2)butalbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (2)codeine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
  
  butalbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)aspirin increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)metolazone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)metoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• mexiletine

  Monitor Closely (1)butalbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (1)mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (2)butalbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (4)midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  midazolam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)midazolam intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  midazolam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (3)butalbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and midodrine both decrease sedation. Use Caution/Monitor.

• midostaurin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  Contraindicated (1)aspirin, mifepristone. Other (see comment). Contraindicated. Comment: Aspirin induced antiplatelet activity may induce excessive bleeding after an abortion w/mifepristone (RU 486).Serious - Use Alternative (1)aspirin will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• milnacipran

  Monitor Closely (1)milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• mirabegron

  Monitor Closely (1)mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (3)butalbital and mirtazapine both increase sedation. Use Caution/Monitor.
  
  codeine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mistletoe

  Monitor Closely (1)aspirin increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mitotane

  Serious - Use Alternative (1)aspirin will decrease the level or effect of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mobocertinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Monitor Closely (3)butalbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and modafinil both decrease sedation. Use Caution/Monitor.

• moexipril

  Monitor Closely (1)moexipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• montelukast

  Minor (1)butalbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• morphine

  Monitor Closely (3)butalbital and morphine both increase sedation. Use Caution/Monitor.
  
  codeine and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  Monitor Closely (3)butalbital and motherwort both increase sedation. Use Caution/Monitor.
  
  codeine and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxisylyte

  Monitor Closely (1)aspirin decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• moxonidine

  Monitor Closely (3)butalbital and moxonidine both increase sedation. Use Caution/Monitor.
  
  codeine and moxonidine both increase sedation. Use Caution/Monitor.
  
  moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mycophenolate

  Monitor Closely (1)aspirin will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  Monitor Closely (3)butalbital and nabilone both increase sedation. Use Caution/Monitor.
  
  codeine and nabilone both increase sedation. Use Caution/Monitor.
  
  nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nabumetone

  Monitor Closely (2)aspirin and nabumetone both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and nabumetone both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (3)nadolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nafcillin

  Monitor Closely (2)nafcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  nafcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (3)butalbital and nalbuphine both increase sedation. Use Caution/Monitor.
  
  codeine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• naldemedine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• naproxen

  Monitor Closely (2)aspirin and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  Monitor Closely (1)butalbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nebivolol

  Monitor Closely (3)aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nebivolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nefazodone

  Monitor Closely (1)nefazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• nelfinavir

  Monitor Closely (1)butalbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• neomycin PO

  Minor (1)aspirin increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• neratinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• nettle

  Monitor Closely (1)aspirin increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)nettle increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nicardipine

  Monitor Closely (1)butalbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  Minor (1)butalbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (1)butalbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• nimodipine

  Minor (1)butalbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nirogacestat

  Serious - Use Alternative (1)butalbital will decrease the level or effect of nirogacestat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nisoldipine

  Monitor Closely (1)butalbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nitazoxanide

  Monitor Closely (1)nitazoxanide, aspirin. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

• nitrendipine

  Minor (1)butalbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nitroglycerin rectal

  Monitor Closely (1)aspirin will increase the level or effect of nitroglycerin rectal by Other (see comment). Use Caution/Monitor. The pharmacological effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

• nitroglycerin sublingual

  Monitor Closely (1)aspirin increases effects of nitroglycerin sublingual by additive vasodilation. Use Caution/Monitor. Vasodilatory and hemodynamic effects of NTG may be enhanced by coadministration with aspirin (additive effect desirable for emergent treatment).

• noni juice

  Minor (1)aspirin and noni juice both increase serum potassium. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (4)norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norgestrel

  Monitor Closely (1)butalbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

• nortriptyline

  Monitor Closely (3)butalbital and nortriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• ofloxacin

  Minor (1)ofloxacin, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• olanzapine

  Monitor Closely (4)butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and olanzapine both increase sedation. Use Caution/Monitor.
  
  codeine and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oliceridine

  Monitor Closely (3)oliceridine, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  butalbital will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.
  
  oliceridine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• olmesartan

  Monitor Closely (3)olmesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• olopatadine intranasal

  Serious - Use Alternative (2)codeine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  butalbital and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• omega 3 carboxylic acids

  Monitor Closely (1)omega 3 carboxylic acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

• omega 3 fatty acids

  Monitor Closely (1)omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• omeprazole

  Monitor Closely (1)butalbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• opium tincture

  Monitor Closely (3)butalbital and opium tincture both increase sedation. Use Caution/Monitor.
  
  codeine and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (2)orphenadrine and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and orphenadrine both increase sedation. Use Caution/Monitor.

• osilodrostat

  Monitor Closely (1)butalbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

• ospemifene

  Monitor Closely (1)aspirin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxacillin

  Monitor Closely (2)oxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  oxacillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• oxaprozin

  Monitor Closely (2)aspirin and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and oxaprozin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxazepam

  Monitor Closely (3)oxazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and oxazepam both increase sedation. Use Caution/Monitor.
  
  oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxybutynin

  Minor (1)butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (3)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and oxycodone both increase sedation. Use Caution/Monitor.
  
  codeine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (3)oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and oxymorphone both increase sedation. Use Caution/Monitor.
  
  codeine and oxymorphone both increase sedation. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (2)ozanimod and codeine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
  
  ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paclitaxel

  Minor (1)butalbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  Minor (1)butalbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paliperidone

  Monitor Closely (3)butalbital and paliperidone both increase sedation. Use Caution/Monitor.
  
  codeine and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• palovarotene

  Serious - Use Alternative (1)butalbital will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• panax ginseng

  Monitor Closely (1)aspirin and panax ginseng both increase anticoagulation. Use Caution/Monitor.

• papaveretum

  Monitor Closely (3)butalbital and papaveretum both increase sedation. Use Caution/Monitor.
  
  codeine and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaverine

  Monitor Closely (2)butalbital and papaverine both increase sedation. Use Caution/Monitor.
  
  codeine and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Monitor Closely (3)aspirin and parecoxib both increase serum potassium. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  aspirin and parecoxib both increase anticoagulation. Use Caution/Monitor.Minor (3)butalbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  aspirin will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  Minor (1)aspirin increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• paroxetine

  Monitor Closely (2)paroxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• passion flower

  Monitor Closely (1)passion flower increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• pau d'arco

  Monitor Closely (1)aspirin and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• pazopanib

  Monitor Closely (1)butalbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pefloxacin

  Monitor Closely (1)pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pegaspargase

  Monitor Closely (1)pegaspargase increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• peginterferon alfa 2a

  Minor (1)peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• peginterferon alfa 2b

  Monitor Closely (1)peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegvisomant

  Monitor Closely (1)codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pemetrexed

  Serious - Use Alternative (1)aspirin increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

• pemigatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• penbutolol

  Monitor Closely (3)butalbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  penbutolol and aspirin both increase serum potassium. Use Caution/Monitor.

• penicillin G aqueous

  Monitor Closely (2)penicillin G aqueous, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  penicillin G aqueous, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• penicillin VK

  Minor (1)penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

• pentazocine

  Monitor Closely (3)butalbital and pentazocine both increase sedation. Use Caution/Monitor.
  
  codeine and pentazocine both increase sedation. Use Caution/Monitor.
  
  pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)pentazocine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.Minor (1)aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

• pentobarbital

  Monitor Closely (3)butalbital and pentobarbital both increase sedation. Use Caution/Monitor.
  
  pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pentobarbital and codeine both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perampanel

  Monitor Closely (1)perampanel and codeine both increase sedation. Use Caution/Monitor.

• perindopril

  Monitor Closely (1)perindopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin,in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• perphenazine

  Monitor Closely (3)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  codeine and perphenazine both increase sedation. Use Caution/Monitor.Minor (2)perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• pexidartinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phendimetrazine

  Monitor Closely (3)butalbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.

• phenelzine

  Contraindicated (1)phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.Serious - Use Alternative (1)phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• phenindione

  Monitor Closely (1)phenindione and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.

• phenobarbital

  Monitor Closely (3)phenobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and phenobarbital both increase sedation. Use Caution/Monitor.
  
  phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phenoxybenzamine

  Monitor Closely (1)aspirin decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phentermine

  Monitor Closely (3)butalbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phentermine both decrease sedation. Use Caution/Monitor.

• phentolamine

  Monitor Closely (1)aspirin decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phenylephrine

  Monitor Closely (3)butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (3)codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
  
  caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Monitor Closely (1)butalbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pholcodine

  Monitor Closely (3)pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and pholcodine both increase sedation. Use Caution/Monitor.
  
  codeine and pholcodine both increase sedation. Use Caution/Monitor.

• phytoestrogens

  Monitor Closely (1)aspirin and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

• pimozide

  Monitor Closely (3)butalbital and pimozide both increase sedation. Use Caution/Monitor.
  
  codeine and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pindolol

  Monitor Closely (3)pindolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  butalbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pioglitazone

  Minor (1)butalbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pipemidic acid

  Minor (1)pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• piperacillin

  Minor (1)piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

• pirbuterol

  Monitor Closely (4)aspirin increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• piroxicam

  Monitor Closely (2)aspirin and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and piroxicam both increase serum potassium. Use Caution/Monitor.Minor (2)aspirin will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• pirtobrutinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

• pitolisant

  Monitor Closely (1)butalbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• pivmecillinam

  Monitor Closely (2)pivmecillinam, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  pivmecillinam, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• polatuzumab vedotin

  Monitor Closely (1)butalbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• posaconazole

  Minor (2)butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• potassium acid phosphate

  Monitor Closely (1)aspirin and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)aspirin and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

• potassium iodide

  Monitor Closely (1)potassium iodide and aspirin both increase serum potassium. Use Caution/Monitor.

• pralsetinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• prasugrel

  Monitor Closely (1)aspirin, prasugrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• prazosin

  Monitor Closely (1)aspirin decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  Monitor Closely (2)butalbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• prednisone

  Monitor Closely (2)aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.
  
  butalbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (2)pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  pregabalin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• pretomanid

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

• primidone

  Monitor Closely (3)primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  primidone and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and primidone both increase sedation. Use Caution/Monitor.Minor (1)primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• probenecid

  Serious - Use Alternative (1)aspirin decreases effects of probenecid by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Aspirin decreases uricosuric action of probenecid.

• procarbazine

  Contraindicated (1)procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.Serious - Use Alternative (1)procarbazine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

• prochlorperazine

  Monitor Closely (3)butalbital and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promethazine

  Monitor Closely (3)promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine and butalbital both increase sedation. Use Caution/Monitor.
  
  promethazine and codeine both increase sedation. Use Caution/Monitor.

• propafenone

  Monitor Closely (1)butalbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.Minor (3)butalbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• propofol

  Monitor Closely (2)propofol and butalbital both increase sedation. Use Caution/Monitor.
  
  propofol and codeine both increase sedation. Use Caution/Monitor.

• propranolol

  Monitor Closely (3)butalbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  propranolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• propylhexedrine

  Monitor Closely (3)butalbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.

• protamine

  Monitor Closely (1)protamine and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)butalbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (3)butalbital and protriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• quazepam

  Monitor Closely (3)quazepam and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  Monitor Closely (4)butalbital and quetiapine both increase sedation. Use Caution/Monitor.
  
  codeine and quetiapine both increase sedation. Use Caution/Monitor.
  
  quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinacrine

  Minor (2)quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• quinapril

  Monitor Closely (1)quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, quinapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• quinidine

  Monitor Closely (2)quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinine

  Minor (1)butalbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quizartinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rabeprazole

  Minor (2)butalbital will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  Monitor Closely (3)butalbital and ramelteon both increase sedation. Use Caution/Monitor.
  
  codeine and ramelteon both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramipril

  Monitor Closely (1)ramipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, ramipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• ranolazine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rasagiline

  Monitor Closely (1)rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.Serious - Use Alternative (1)rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• regadenoson

  Serious - Use Alternative (1)caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

• reishi

  Monitor Closely (1)aspirin and reishi both increase anticoagulation. Use Caution/Monitor.

• remimazolam

  Monitor Closely (2)remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
  
  remimazolam, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

  Monitor Closely (1)butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• repotrectinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• reteplase

  Monitor Closely (1)aspirin, reteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (1)rifampin decreases levels of butalbital by increasing metabolism. Use Caution/Monitor.Minor (1)rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• riluzole

  Minor (1)butalbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• rimegepant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• risperidone

  Monitor Closely (3)butalbital and risperidone both increase sedation. Use Caution/Monitor.
  
  codeine and risperidone both increase sedation. Use Caution/Monitor.
  
  risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ritonavir

  Monitor Closely (2)ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rivaroxaban

  Monitor Closely (1)aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• rivastigmine

  Monitor Closely (1)rivastigmine increases toxicity of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rose hips

  Minor (4)aspirin decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.
  
  rose hips will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.
  
  rose hips increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

• sacubitril/valsartan

  Monitor Closely (3)sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

• sage

  Minor (3)butalbital and sage both increase sedation. Minor/Significance Unknown.
  
  codeine and sage both increase sedation. Minor/Significance Unknown.
  
  sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• salicylates (non-asa)

  Monitor Closely (2)aspirin and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (4)butalbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

• salsalate

  Monitor Closely (2)aspirin and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salsalate both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• saquinavir

  Monitor Closely (1)butalbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• saw palmetto

  Monitor Closely (1)saw palmetto increases toxicity of aspirin by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

• saxagliptin

  Minor (1)butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• scullcap

  Monitor Closely (3)butalbital and scullcap both increase sedation. Use Caution/Monitor.
  
  codeine and scullcap both increase sedation. Use Caution/Monitor.
  
  scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• secobarbital

  Monitor Closely (3)secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and secobarbital both increase sedation. Use Caution/Monitor.
  
  secobarbital and codeine both increase sedation. Use Caution/Monitor.Minor (1)secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• selegiline

  Monitor Closely (2)selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
  
  selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)selegiline transdermal increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.Serious - Use Alternative (1)selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  Serious - Use Alternative (2)selinexor, codeine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
  
  selinexor, butalbital. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selumetinib

  Monitor Closely (1)aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.Serious - Use Alternative (1)butalbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sertraline

  Monitor Closely (2)sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.Minor (1)sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• sevoflurane

  Monitor Closely (1)sevoflurane and codeine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (3)butalbital and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  codeine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• sildenafil

  Monitor Closely (1)butalbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• silodosin

  Monitor Closely (1)aspirin decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.Serious - Use Alternative (1)butalbital will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  Serious - Use Alternative (1)butalbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  Serious - Use Alternative (1)butalbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• smoking

  Minor (1)smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• sodium bicarbonate

  Minor (1)sodium bicarbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• sodium citrate/citric acid

  Minor (1)sodium citrate/citric acid, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• sodium oxybate

  Serious - Use Alternative (2)codeine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  butalbital, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  Monitor Closely (1)aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• solifenacin

  Monitor Closely (1)butalbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• solriamfetol

  Monitor Closely (1)caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)butalbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• sotalol

  Monitor Closely (3)aspirin decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  sotalol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• sparsentan

  Monitor Closely (1)aspirin and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.

• spironolactone

  Monitor Closely (2)aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.
  
  spironolactone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• stiripentol

  Monitor Closely (2)stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.Serious - Use Alternative (2)butalbital will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.
  
  stiripentol, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.Minor (1)aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• streptomycin

  Minor (1)aspirin increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• succinylcholine

  Monitor Closely (1)aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.

• sufentanil

  Monitor Closely (3)butalbital and sufentanil both increase sedation. Use Caution/Monitor.
  
  codeine and sufentanil both increase sedation. Use Caution/Monitor.
  
  sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sufentanil SL

  Monitor Closely (1)butalbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.Serious - Use Alternative (2)sufentanil SL, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  sufentanil SL, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfadiazine

  Minor (1)aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Monitor Closely (1)aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.Minor (1)butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sulfasalazine

  Monitor Closely (2)aspirin and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulfasalazine both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  Minor (1)aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)aspirin and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulindac both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sunitinib

  Monitor Closely (1)butalbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tacrolimus

  Monitor Closely (1)butalbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

  Monitor Closely (1)butalbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tafluprost

  Monitor Closely (1)tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tamoxifen

  Minor (1)butalbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• tapentadol

  Monitor Closely (3)butalbital and tapentadol both increase sedation. Use Caution/Monitor.
  
  codeine and tapentadol both increase sedation. Use Caution/Monitor.
  
  tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tazemetostat

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• telmisartan

  Monitor Closely (3)telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.

• temazepam

  Monitor Closely (3)butalbital and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  temazepam and codeine both increase sedation. Use Caution/Monitor.

• temocillin

  Monitor Closely (2)temocillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  temocillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• temsirolimus

  Monitor Closely (1)butalbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tenecteplase

  Monitor Closely (1)aspirin, tenecteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• teniposide

  Minor (1)aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

• terazosin

  Monitor Closely (1)aspirin decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• terbinafine

  Monitor Closely (2)terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
  
  butalbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbutaline

  Monitor Closely (4)butalbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
  
  aspirin increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tezacaftor

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• thalidomide

  Monitor Closely (1)thalidomide increases effects of butalbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

• theophylline

  Monitor Closely (2)butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thiamine

  Minor (1)caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  Monitor Closely (4)thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  butalbital and thioridazine both increase sedation. Use Caution/Monitor.
  
  codeine and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown.
  
  thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• thiothixene

  Monitor Closely (3)butalbital and thiothixene both increase sedation. Use Caution/Monitor.
  
  codeine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thyroid desiccated

  Minor (1)butalbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

• tibolone

  Minor (1)butalbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• ticagrelor

  Monitor Closely (1)aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.Serious - Use Alternative (1)codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• ticarcillin

  Monitor Closely (2)ticarcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  ticarcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ticlopidine

  Monitor Closely (1)ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)aspirin increases effects of ticlopidine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced risk of hemorrhage.

• tiludronate

  Minor (1)aspirin decreases levels of tiludronate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• timolol

  Monitor Closely (3)timolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  butalbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
  
  aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• tinidazole

  Monitor Closely (1)butalbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)butalbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tirofiban

  Monitor Closely (1)aspirin, tirofiban. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• tivozanib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tizanidine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• tobacco use

  Minor (1)tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tobramycin

  Minor (1)aspirin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• tobramycin inhaled

  Monitor Closely (1)tobramycin inhaled and aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  Monitor Closely (1)aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolbutamide

  Monitor Closely (1)aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (2)butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolfenamic acid

  Monitor Closely (2)aspirin and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolfenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (2)aspirin and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolmetin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (1)butalbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  Monitor Closely (1)aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• topiramate

  Monitor Closely (3)topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• torsemide

  Monitor Closely (1)aspirin increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  Monitor Closely (3)butalbital and tramadol both increase sedation. Use Caution/Monitor.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.
  
  tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• trandolapril

  Monitor Closely (1)trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.Serious - Use Alternative (1)aspirin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Monitor Closely (1)tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.Serious - Use Alternative (1)tranylcypromine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• travoprost ophthalmic

  Monitor Closely (1)travoprost ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  Monitor Closely (5)trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  butalbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and trazodone both increase sedation. Use Caution/Monitor.
  
  codeine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triamcinolone acetonide injectable suspension

  Monitor Closely (2)aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.
  
  butalbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• triamterene

  Monitor Closely (1)triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.Minor (2)triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• triazolam

  Monitor Closely (4)butalbital and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  triazolam and codeine both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (3)triclofos and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (3)butalbital and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trimipramine

  Monitor Closely (3)butalbital and trimipramine both increase sedation. Use Caution/Monitor.
  
  codeine and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triprolidine

  Monitor Closely (3)triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  triprolidine and butalbital both increase sedation. Use Caution/Monitor.
  
  triprolidine and codeine both increase sedation. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ubrogepant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

• valbenazine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

• valerian

  Serious - Use Alternative (3)valerian and butalbital both increase sedation. Avoid or Use Alternate Drug.
  
  valerian and codeine both increase sedation. Avoid or Use Alternate Drug.
  
  valerian increases effects of butalbital by pharmacodynamic synergism. Avoid or Use Alternate Drug. May enhance CNS depression.

• valganciclovir

  Minor (1)aspirin will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valproic acid

  Monitor Closely (1)aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

• valsartan

  Monitor Closely (3)valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

• vancomycin

  Minor (1)aspirin increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• vardenafil

  Monitor Closely (1)butalbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• varicella virus vaccine live

  Serious - Use Alternative (1)aspirin, varicella virus vaccine live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• venlafaxine

  Monitor Closely (2)venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.Minor (1)venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• verapamil

  Monitor Closely (1)butalbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.
  
  verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• vinblastine

  Minor (1)butalbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine

  Minor (1)butalbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  Minor (1)butalbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  Minor (1)butalbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• voclosporin

  Monitor Closely (1)voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.Serious - Use Alternative (1)butalbital will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  Serious - Use Alternative (1)butalbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vorapaxar

  Monitor Closely (2)aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.
  
  aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• voriconazole

  Serious - Use Alternative (1)butalbital decreases levels of voriconazole by increasing metabolism. Contraindicated.Minor (3)butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• vortioxetine

  Monitor Closely (1)aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

• voxelotor

  Serious - Use Alternative (1)butalbital will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).

• warfarin

  Monitor Closely (2)aspirin increases effects of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Avoid coadministration of chronic high-dose aspirin. Aspirin's antiplatelet properties may increase anticoagulation effect of warfarin. The need for simultaneous use of low-dose aspirin and warfarin is common for patients with cardiovascular disease. .
  
  butalbital will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inducers of these isoenzymes and adjust warfarin dose if needed.

• willow bark

  Minor (2)aspirin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  willow bark increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

• xylometazoline

  Monitor Closely (3)butalbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

• yerba mate

  Minor (1)yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• yohimbine

  Monitor Closely (3)butalbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and yohimbine both decrease sedation. Use Caution/Monitor.

• zafirlukast

  Minor (1)aspirin increases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

• zaleplon

  Minor (1)butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zanubrutinib

  Monitor Closely (1)aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.Serious - Use Alternative (2)butalbital will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  butalbital will decrease the level or effect of zanubrutinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

• ziconotide

  Monitor Closely (3)butalbital and ziconotide both increase sedation. Use Caution/Monitor.
  
  codeine and ziconotide both increase sedation. Use Caution/Monitor.
  
  ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• zileuton

  Minor (1)zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ziprasidone

  Monitor Closely (3)butalbital and ziprasidone both increase sedation. Use Caution/Monitor.
  
  codeine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zoledronic acid

  Minor (1)aspirin decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• zolpidem

  Minor (1)butalbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  Minor (1)butalbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zotepine

  Monitor Closely (3)aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  butalbital and zotepine both increase sedation. Use Caution/Monitor.
  
  codeine and zotepine both increase sedation. Use Caution/Monitor.