codeine/acetaminophen/butalbital/caffeine (Rx)

Tension Headache

1-2 tab/cap PO q4hr; not to exceed 6 tab/cap 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 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

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

Limitation 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

Access to naloxone for opioid overdose

• Assess need for naloxone upon initiating and renewing treatment

• Consider prescribing naloxone

  • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
  • Household members (including children) or other close contacts at risk for accidental ingestion or overdose

• Consult patients and caregivers on the following:

  • Availability of naloxone for emergency treatment of opioid overdose
  • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

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

Tension Headache (Off-label)

<12 years: Safety and efficacy not established

≥12 years: 1-2 tab/cap PO q4hr; not to exceed 6 tab/cap per day (not to exceed acetaminophen 4 g/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 (3)

• 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.

• 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

Serious - Use Alternative (99)

• 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.

• 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.

• 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. .

• 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, 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, 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

  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, 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• lonafarnib

  acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• 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.

• mestranol

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

• 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.

• 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.

• 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.

• pexidartinib

  acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• pretomanid

  acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• regadenoson

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

Monitor Closely (467)

• 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

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

• albuterol

  codeine 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.

• 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.

• alfentanil

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

• acrivastine

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

• albuterol

  butalbital increases and albuterol 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.

• 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.

• 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.

• apalutamide

  apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• apomorphine

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

• arformoterol

  arformoterol and caffeine both decrease 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.

• arformoterol

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

• 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.

• atogepant

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

• avapritinib

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

• axitinib

  acetaminophen increases levels of axitinib 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

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

• azelastine

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

• 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 butalbital both increase sedation. Use Caution/Monitor.

• baclofen

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

• 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.

• benazepril

  butalbital increases toxicity of benazepril by unspecified interaction mechanism. 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

  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.

• brexanolone

  brexanolone, codeine. Either increases toxicity of the other by sedation. 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.

• brexpiprazole

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

• brimonidine

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

• 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.

• bupivacaine implant

  acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• 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.

• busulfan

  acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• 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.

• 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.

• 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.

• celecoxib

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

• celiprolol

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

• chlorpheniramine

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

• chlorpheniramine

  chlorpheniramine and codeine both increase sedation. 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.
  
  chlorpromazine increases and caffeine decreases sedation. 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.

• cinnarizine

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

• cilostazol

  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.

• 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.

• ciprofloxacin

  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.

• clemastine

  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

  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

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

• clomipramine

  butalbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and clomipramine both increase sedation. 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

  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.

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

• clorazepate

  clorazepate and codeine both increase sedation. 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.
  
  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

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

• codeine

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

• colchicine

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

• 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.

• cortisone

  butalbital will decrease the level or effect of cortisone 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.
  
  cyclizine and codeine both increase sedation. Use Caution/Monitor.
  
  cyclizine and butalbital both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

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

• cyproheptadine

  cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

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

• dantrolene

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

• dapsone topical

  acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

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

• 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.

• 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

• dexchlorpheniramine

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

• 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.

• 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.
  
  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 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

  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

  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.

• dextromoramide

  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

  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

  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.

• diethylpropion

  caffeine and diethylpropion both decrease 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.

• diethylpropion

  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.

• difelikefalin

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

• difenoxin hcl

  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.

• 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

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

• dimenhydrinate

  dimenhydrinate and butalbital both increase sedation. 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.
  
  diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

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

• dopamine

  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

  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.

• 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.

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

• 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

  eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  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.

• exenatide injectable solution

  exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• 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.

• epinephrine

  epinephrine and caffeine both decrease sedation. 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.

• epinephrine racemic

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

• erlotinib

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

• esketamine intranasal

  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. .

• escitalopram

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

• estazolam

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

• esketamine intranasal

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

• esmolol

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

• estradiol

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

• ethanol

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

• ethinylestradiol

  ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

• ethotoin

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

• exenatide injectable suspension

  exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• 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.

• 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.

• fesoterodine

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

• fexinidazole

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

• finerenone

  acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• flibanserin

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

• imatinib

  imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.

• fludrocortisone

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

• fluoxetine

  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

  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.

• fluvoxamine

  fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.

• formoterol

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

• fosamprenavir

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

• 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.

• 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.

• 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.

• hops

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

• hydrocortisone

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

• hydromorphone

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

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

• hydroxyzine

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

• iloperidone

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

• 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.

• 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 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.

• indinavir

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

• isavuconazonium sulfate

  acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isoniazid

  isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

• isoproterenol

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

• 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.

• ivacaftor

  acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• ixabepilone

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

• ketotifen, ophthalmic

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

• labetalol

  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.

• lemborexant

  acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

• letermovir

  letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• 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.

• 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 codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  levalbuterol and caffeine both decrease sedation. 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.

• 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.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levorphanol

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

• 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.

• lixisenatide (DSC)

  lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

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

• lomitapide

  acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• 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.

• 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.

• melatonin

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

• mestranol

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

• metaproterenol

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

• metaproterenol

  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.

• 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.
  
  methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.
  
  caffeine and methamphetamine both decrease sedation. 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.

• 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.

• midazolam

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

• midazolam intranasal

  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• midodrine

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

• mexiletine

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

• midazolam

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

• mipomersen

  mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• 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.

• 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.

• 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.

• moxonidine

  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.

• 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.

• nadolol

  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.

• nalbuphine

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

• nalbuphine

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

• nalbuphine

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

• nateglinide

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

• nebivolol

  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.

• nelfinavir

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

• norepinephrine

  norepinephrine and caffeine both decrease sedation. 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.

• 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.
  
  olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

• opium tincture

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

• omeprazole

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

• opium tincture

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

• opium tincture

  butalbital and opium tincture both increase sedation. 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.

• oxazepam

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

• oxycodone

  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.

• papaveretum

  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

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

• pefloxacin

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

• parecoxib

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

• paroxetine

  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.

• pazopanib

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

• 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.

• 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.

• 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.

• phenobarbital

  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.

• phentermine

  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.

• 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.
  
  caffeine and phenylephrine both decrease sedation. 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.

• 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

  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

  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.

• 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.

• 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.

• prednisolone

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

• prednisone

  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.
  
  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.
  
  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.
  
  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.

• propylhexedrine

  caffeine and propylhexedrine both decrease sedation. 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

  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.

• protriptyline

  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.

• 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.

• 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.

• rasagiline

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

• 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.

• 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.

• 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.

• 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.

• salmeterol

  butalbital increases and salmeterol decreases sedation. 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.

• saquinavir

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

• 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.

• shepherd's purse

  butalbital 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.

• sertraline

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

• solriamfetol

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

• 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.

• solifenacin

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

• sorafenib

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

• sotalol

  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.

• 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.

• sufentanil

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

• 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.

• tapentadol

  tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

• tapentadol

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

• tazemetostat

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

• temazepam

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

• temsirolimus

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

• terbutaline

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

• 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

  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.

• teriflunomide

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

• tetracaine

  tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thalidomide

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

• 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.
  
  thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

• thiothixene

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

• 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

  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.

• tinidazole

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

• tipranavir

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

• warfarin

  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

Minor (204)

• acetazolamide

  acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• adenosine

  caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• albiglutide

  albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• alfentanil

  butalbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• 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.

• 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.

• antipyrine

  butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• argatroban

  acetaminophen increases effects of argatroban by unknown mechanism. 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

  butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• bemiparin

  acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• bivalirudin

  acetaminophen increases effects of bivalirudin by unknown mechanism. 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.

• ashwagandha

  ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• 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.

• 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

  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.

• 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.
  
  carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• celecoxib

  butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cholestyramine

  cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cevimeline

  butalbital will decrease the level or effect of cevimeline 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.

• chlorpromazine

  butalbital decreases levels of chlorpromazine by increasing metabolism. 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.

• clonazepam

  clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• colestipol

  colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• dalteparin

  acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• dapsone

  butalbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• dextroamphetamine

  dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• diazepam

  diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• diclofenac

  butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• disopyramide

  butalbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• disulfiram

  disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• 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.

• enoxaparin

  acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• eplerenone

  butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• erythromycin base

  erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin lactobionate

  butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin stearate

  butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ethanol

  ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethosuximide

  ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• eucalyptus

  eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• felbamate

  felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• eucalyptus

  butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• finasteride

  butalbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluconazole

  fluconazole increases levels of caffeine by decreasing metabolism. 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

  butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fondaparinux

  acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• fosphenytoin

  fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• frovatriptan

  butalbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• galantamine

  butalbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• grapefruit

  grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• green tea

  green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• 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.

• heparin

  acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• ibuprofen

  butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. 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.

• 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.

• isoniazid

  isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• itraconazole

  itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• lacosamide

  lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ketoconazole

  ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• lamotrigine

  lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levetiracetam

  levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levoketoconazole

  levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• lidocaine

  lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• 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.

• liraglutide

  liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. 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.

• lorazepam

  lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• meloxicam

  butalbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• methazolamide

  methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methsuximide

  methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• metoclopramide

  metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• mexiletine

  mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. 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.

• modafinil

  modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• montelukast

  butalbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• 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.

• oxcarbazepine

  oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin topical

  oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• paclitaxel

  butalbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin transdermal

  oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. 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.

• peginterferon alfa 2a

  peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• 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.

• phenelzine

  phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• phenindione

  acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phenytoin

  phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• piroxicam

  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.

• primidone

  primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.

• protamine

  acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

• 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.

• rifabutin

  rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• riluzole

  butalbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• rufinamide

  rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rose hips

  butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

• ruxolitinib

  acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• saxagliptin

  butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• secobarbital

  secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

• sufentanil

  butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sulfamethoxazole

  butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tamoxifen

  butalbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• tiagabine

  tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• tolbutamide

  butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• topiramate

  topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• tranylcypromine

  tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• valproic acid

  valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• 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.

• venlafaxine

  venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• verapamil

  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.

• 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.
  
  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.

• yerba mate

  yerba mate increases effects of caffeine by pharmacodynamic synergism. 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.

• zonisamide

  zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

• 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.

• acalabrutinib

  Monitor Closely (1)butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• acebutolol

  Monitor Closely (1)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.

• acetazolamide

  Minor (2)acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• 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

• adenosine

  Minor (1)caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• albiglutide

  Minor (1)albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• albuterol

  Monitor Closely (3)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.
  
  albuterol and caffeine both decrease sedation. 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

  Minor (1)butalbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• 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.

• 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.

• 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.

• antipyrine

  Minor (1)butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Serious - Use Alternative (1)butalbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  Serious - Use Alternative (1)butalbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• 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 (3)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.
  
  arformoterol and caffeine both decrease sedation. Use Caution/Monitor.

• argatroban

  Serious - Use Alternative (1)butalbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

• 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 (1)butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• asenapine

  Monitor Closely (1)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 (1)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

  Monitor Closely (2)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.
  
  acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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 (2)acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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

• axitinib

  Monitor Closely (1)acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• baclofen

  Monitor Closely (2)baclofen and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and baclofen both increase sedation. Use Caution/Monitor.

• 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

  Serious - Use Alternative (1)butalbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• benazepril

  Monitor Closely (1)butalbital increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor.

• 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 (1)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.

• bisoprolol

  Monitor Closely (1)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

  Serious - Use Alternative (1)butalbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• 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

  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.

• bupivacaine implant

  Monitor Closely (1)acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• 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.

• busulfan

  Monitor Closely (1)acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• 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 (1)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.

• 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.

• captopril

  Monitor Closely (1)butalbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

• carbamazepine

  Monitor Closely (1)butalbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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 (2)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.

• celecoxib

  Monitor Closely (1)celecoxib 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 celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (1)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.

• 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.

• 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.

• chlorzoxazone

  Monitor Closely (2)chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cholestyramine

  Minor (1)cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. 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 (1)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.

• 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 (1)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.

• 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 (6)butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  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.Minor (1)clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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 (1)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

  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.

• colestipol

  Minor (1)colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• 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.

• cortisone

  Monitor Closely (1)butalbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• 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.

• 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

  Serious - Use Alternative (1)butalbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of dalteparin by unknown mechanism. 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.

• dapsone topical

  Monitor Closely (1)acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

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

• deflazacort

  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.

• 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.

• 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.

• dexamethasone

  Monitor Closely (1)butalbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.Minor (1)diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• diclofenac

  Minor (1)butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• 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.

• 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.

• 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

  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.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (3)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.

• 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.

• 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 (3)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.

• 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.

• 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 (1)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.

• 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 (3)eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 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 (1)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.

• enoxaparin

  Serious - Use Alternative (1)butalbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• ephedrine

  Monitor Closely (3)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 (3)epinephrine and caffeine both decrease sedation. 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 (3)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.
  
  epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• eplerenone

  Minor (1)butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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 (2)erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  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 (2)butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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 (2)butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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 (2)butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.
  
  erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• escitalopram

  Monitor Closely (1)butalbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• 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 (1)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.

• 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 (2)ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• ethosuximide

  Minor (2)ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  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.

• 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.

• exenatide injectable solution

  Monitor Closely (1)exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  Monitor Closely (1)exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• 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.

• felbamate

  Minor (1)felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• felodipine

  Monitor Closely (1)butalbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• fentanyl

  Serious - Use Alternative (2)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 (2)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, 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

  Serious - Use Alternative (2)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, 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.

• 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

  Monitor Closely (1)acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.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.

• flibanserin

  Monitor Closely (3)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.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• 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 (1)butalbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  Monitor Closely (1)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

  Minor (1)butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• fondaparinux

  Serious - Use Alternative (1)butalbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• formoterol

  Monitor Closely (3)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.
  
  formoterol and caffeine both decrease sedation. 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.

• fosphenytoin

  Monitor Closely (1)butalbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• 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.

• 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.

• 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 (1)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.Minor (1)green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• griseofulvin

  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

  Serious - Use Alternative (1)butalbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• hops

  Monitor Closely (1)hops increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• 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 (1)butalbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• ibuprofen

  Minor (1)butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  Minor (1)butalbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• 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 decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.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.

• 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.

• indinavir

  Monitor Closely (1)butalbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• 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.

• isavuconazonium sulfate

  Contraindicated (1)butalbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (1)acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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 (2)isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.
  
  isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (2)isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (3)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.

• 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.

• ivacaftor

  Monitor Closely (1)acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• 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.

• 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.

• labetalol

  Monitor Closely (1)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.

• lacosamide

  Minor (1)lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lamotrigine

  Minor (1)lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• 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.

• 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 (2)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.
  
  acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.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.

• 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 (3)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.

• levetiracetam

  Minor (1)levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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 (3)levoketoconazole increases levels of caffeine by decreasing 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.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (3)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.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.
  
  levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.

• 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.

• liraglutide

  Minor (1)liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. 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.

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• 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.

• lomitapide

  Monitor Closely (1)acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• 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.Serious - Use Alternative (1)acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• 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.Minor (1)lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• losartan

  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 (1)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.

• 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.

• melatonin

  Monitor Closely (3)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

  Minor (1)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.

• 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 (3)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

  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.

• methoxyflurane

  Serious - Use Alternative (1)butalbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

• methsuximide

  Minor (2)methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  methsuximide decreases effects of butalbital by pharmacodynamic antagonism. 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 (1)butalbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metoclopramide

  Minor (1)metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. 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.

• metoprolol

  Monitor Closely (1)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.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• 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 (3)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.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
  
  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.

• mipomersen

  Monitor Closely (1)mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• 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.

• 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.Minor (1)modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• 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.

• 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.

• 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.

• nadolol

  Monitor Closely (1)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.

• 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.

• 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 (1)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.

• nelfinavir

  Monitor Closely (1)butalbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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

  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.

• nisoldipine

  Monitor Closely (1)butalbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• norepinephrine

  Monitor Closely (3)norepinephrine and caffeine both decrease sedation. 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.

• 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.

• 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.

• 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.

• 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.

• oxcarbazepine

  Minor (1)oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  Minor (2)oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin topical

  Minor (1)oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Minor (1)oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. 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.

• 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 (1)butalbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (2)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.

• paroxetine

  Monitor Closely (1)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.

• 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.

• 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.

• 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 (1)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.

• 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.

• 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.

• 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 (2)acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.
  
  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

  Serious - Use Alternative (1)butalbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• 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 (2)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• 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.

• 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.Minor (1)phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• 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 (1)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.

• pirbuterol

  Monitor Closely (3)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

  Minor (1)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.

• 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.

• 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

  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

• prednisolone

  Monitor Closely (1)butalbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• prednisone

  Monitor Closely (1)butalbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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 (2)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.
  
  acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• 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 (2)primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• 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 (1)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

  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

  Serious - Use Alternative (1)butalbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.Minor (1)acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

• 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.

• 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.

• 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.

• 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.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Minor (1)rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  Monitor Closely (1)rifampin decreases levels of butalbital by increasing metabolism. Use Caution/Monitor.Minor (2)rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• 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 (1)butalbital decreases levels of rose hips by increasing elimination. 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.

• rufinamide

  Minor (1)rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ruxolitinib

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• salmeterol

  Monitor Closely (3)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.
  
  salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

• saquinavir

  Monitor Closely (1)butalbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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

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

  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 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.

• 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 (1)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.

• 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.

• 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.

• sulfamethoxazole

  Minor (1)butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. 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.

• 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

  Monitor Closely (1)acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.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.

• 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.

• temsirolimus

  Monitor Closely (1)butalbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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 (3)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.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetracaine

  Monitor Closely (1)tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• 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.

• tiagabine

  Minor (1)tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• tibolone

  Minor (1)butalbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• ticagrelor

  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

• 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.

• timolol

  Monitor Closely (1)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.

• tinidazole

  Monitor Closely (2)butalbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  acetaminophen will increase 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.

• 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.

• tolbutamide

  Minor (1)butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. 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

  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 (2)topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• 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.

• 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.

• trazodone

  Monitor Closely (4)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 (1)butalbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• 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.

• valproic acid

  Minor (1)valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• vardenafil

  Monitor Closely (1)butalbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• venlafaxine

  Monitor Closely (1)venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.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 (1)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

  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.

• 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.

• 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)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.
  
  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• 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.

• zaleplon

  Minor (1)butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zanubrutinib

  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.

• zolpidem

  Minor (1)butalbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  Minor (2)butalbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

• zotepine

  Monitor Closely (2)butalbital and zotepine both increase sedation. Use Caution/Monitor.
  
  codeine and zotepine both increase sedation. Use Caution/Monitor.