butalbital/aspirin/caffeine/codeine (Rx)

Brand and Other Names:Fiorinal with Codeine
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

butalbital/aspirin/caffeine/codeine

capsule: Schedule III

  • 50mg/325mg/40mg/30mg

Tension Headache

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

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

Limitations of Use

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

Dosing Considerations

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

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

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

Dosage Forms & Strengths

capsule: Schedule III

  • 50mg/325mg/40mg/30mg

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

Tension Headache

<16 years: Safety and efficacy not established

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

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

Use caution; barbiturates not recommended in the elderly

Tension Headache

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

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

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Interactions

Interaction Checker

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            Contraindicated (7)

            • alvimopan

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

            • dichlorphenamide

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

            • doravirine

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

            • isocarboxazid

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

            • linezolid

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

            • mifepristone

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

            • phenelzine

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

            Serious - Use Alternative (94)

            • abametapir

              abametapir will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

            • 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.

            • acalabrutinib

              butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.

            • 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.

            • 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.

            • avapritinib

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

            • bemiparin

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

            • benazepril

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

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, 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, 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.

            • 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.

            • 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.

            • 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.

            • 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

              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.

            • captopril

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

            • clonidine

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

            • copanlisib

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

            • dacomitinib

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

            • dalteparin

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

            • 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.

            • eluxadoline

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

            • enalapril

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

            • enoxaparin

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

            • erdafitinib

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

            • ergotamine

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • everolimus

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

            • fedratinib

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

            • fentanyl

              fentanyl, 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.

            • fosinopril

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

            • givosiran

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

            • finerenone

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

            • fondaparinux

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

            • fostamatinib

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

            • glasdegib

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

            • heparin

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

            • hydrocodone

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

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

            • ibuprofen

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

              ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

            • ibuprofen IV

              ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

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

            • infigratinib

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

            • iobenguane I 131

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

            • isocarboxazid

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

            • isocarboxazid

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

            • istradefylline

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

            • ivosidenib

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

            • ketorolac

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

            • ketorolac intranasal

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

            • larotrectinib

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

            • lefamulin

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

            • lemborexant

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

              lemborexant, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

            • lesinurad

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

            • linezolid

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

            • lisinopril

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

            • lovastatin

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

            • lurbinectedin

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

            • macimorelin

              butalbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

              aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

            • measles, mumps, rubella and varicella vaccine, live

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

            • mestranol

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

            • methotrexate

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

            • methoxyflurane

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

            • methylene blue

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

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

            • metoclopramide intranasal

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

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

            • midostaurin

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

            • mifepristone

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

            • mitotane

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

            • moexipril

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

            • nalbuphine

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

            • mobocertinib

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

            • naldemedine

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

            • neratinib

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

            • 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.

            • pemetrexed

              aspirin increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

            • regadenoson

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

            Monitor Closely (685)

            • abciximab

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

            • abiraterone

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

            • acalabrutinib

              acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.

            • acebutolol

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

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

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

            • aceclofenac

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

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

            • albuterol

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

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

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

            • acemetacin

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

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

            • alfentanil

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

            • acetazolamide

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

              acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • agrimony

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

            • albuterol

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

            • alfalfa

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

            • alfentanil

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

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

            • alfuzosin

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

            • aliskiren

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

            • alitretinoin

              butalbital will decrease the level or effect of alitretinoin 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.

            • almotriptan

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

            • amitriptyline

              amitriptyline 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.

            • alteplase

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

            • American ginseng

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

            • amiloride

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

            • amiodarone

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

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

            • 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.

              codeine 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

              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.

            • amoxapine

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

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

            • amoxicillin

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

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

            • ampicillin

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

            • anagrelide

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

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

            • antithrombin alfa

              antithrombin alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

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

            • antithrombin III

              antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

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

            • apixaban

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

            • apomorphine

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

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

            • aprepitant

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

            • arformoterol

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

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

              arformoterol and caffeine both decrease sedation. 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.

            • argatroban

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

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

            • aripiprazole

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

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

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

            • armodafinil

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

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

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

            • artemether/lumefantrine

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

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

            • azelastine

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

            • asenapine

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

            • atenolol

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

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

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

            • azelastine

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

            • azficel-T

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

            • 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

            • azelastine

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

            • azilsartan

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

              aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • 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.

            • bemiparin

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

            • benazepril

              butalbital increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor.

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

            • bendroflumethiazide

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

            • benperidol

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

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

            • benzphetamine

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

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

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

            • betaxolol

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

              aspirin decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • brompheniramine

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

            • betrixaban

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

            • bisoprolol

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

            • bortezomib

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

            • brexanolone

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

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

            • bimatoprost

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

            • brompheniramine

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

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

            • bisoprolol

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

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

            • bivalirudin

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

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

            • brinzolamide

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

            • budesonide

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

            • bumetanide

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

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

            • buprenorphine

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

            • buprenorphine

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

            • buprenorphine buccal

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

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

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

            • buprenorphine, long-acting injection

              butalbital increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

              codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

              butalbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • butabarbital

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

            • bupropion

              butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

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

            • buspirone

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

            • butabarbital

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

            • butabarbital

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

            • butalbital

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

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

            • butorphanol

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

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

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

            • caffeine

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

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

            • carbinoxamine

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

            • candesartan

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

              aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

            • cannabidiol

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

            • caplacizumab

              caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • captopril

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

            • carbenoxolone

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

            • carbinoxamine

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

            • captopril

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

            • carbamazepine

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

            • carbinoxamine

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

            • carisoprodol

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

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

            • carvedilol

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

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

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

              aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • celecoxib

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

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

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

            • celiprolol

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

              aspirin decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              butalbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • cenobamate

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

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorothiazide

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

            • chloral hydrate

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

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

            • chlordiazepoxide

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

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

            • chloroquine

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

            • chlorpheniramine

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

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

            • chlorpheniramine

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

            • chlorpromazine

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

            • chlorpromazine

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

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

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

            • chlorpropamide

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

            • chlorthalidone

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

            • chlorzoxazone

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

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

            • choline magnesium trisalicylate

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

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

            • cilostazol

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

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

            • cimetidine

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

            • cinnamon

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

            • cinacalcet

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

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

            • cinnarizine

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

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

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

            • ciprofloxacin

              aspirin decreases levels of ciprofloxacin by Other (see comment). Use Caution/Monitor. Comment: Buffered aspirin may decrease absorption of quinolones. Consider administering 2 hr before or 6 hr after, buffered aspirin administration.

              ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

            • citalopram

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

            • clemastine

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

            • clemastine

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

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

            • clobazam

              codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

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

            • clobetasone

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

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

            • clomipramine

              butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

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

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

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

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

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

              clomipramine 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

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

            • clorazepate

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

            • clopidogrel

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

            • clorazepate

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

            • clorazepate

              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

              cocaine 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.

            • collagenase clostridium histolyticum

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

            • conivaptan

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

            • conjugated estrogens

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

            • conjugated estrogens, vaginal

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

            • cordyceps

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

            • cortisone

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

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

            • cyclizine

              cyclizine 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.

            • cyclopenthiazide

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

            • cyproheptadine

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

            • cyclobenzaprine

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

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

            • cyclosporine

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

            • cyproheptadine

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

            • cyproheptadine

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

            • dabigatran

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

            • dalteparin

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

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

            • dantrolene

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

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

            • darifenacin

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

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

            • darunavir

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

            • deferasirox

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

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

            • defibrotide

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

            • desipramine

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

            • deflazacort

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

            • desflurane

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

            • dasatinib

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

            • desipramine

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

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

              desipramine 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 desipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • desirudin

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

            • desvenlafaxine

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

            • deutetrabenazine

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

            • deutetrabenazine

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

            • dexamethasone

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

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

            • dexchlorpheniramine

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

              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.

            • dexfenfluramine

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

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

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

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

            • dextroamphetamine

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

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

            • dextromoramide

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

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

            • diamorphine

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

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

            • diazepam

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

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

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

            • diazepam intranasal

              butalbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.

              diazepam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • diclofenac

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

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromoramide

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

            • diamorphine

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

            • dicloxacillin

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

            • diethylpropion

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

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

            • diethylpropion

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

            • difenoxin hcl

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

            • difenoxin hcl

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

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

            • diflunisal

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

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

            • digoxin

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

            • diltiazem

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

            • dimenhydrinate

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

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenhydramine

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

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

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

            • diphenoxylate hcl

              butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

              codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

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

            • dipipanone

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

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

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

            • dipyridamole

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

            • dobutamine

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

            • dobutamine

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

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

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

            • dong quai

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

            • dopamine

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

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

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

            • dopexamine

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

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

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

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

            • dosulepin

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

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

            • doxepin

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

            • doxazosin

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

            • doxepin

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

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

            • doxycycline

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

            • doxylamine

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

            • doxylamine

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

            • dronabinol

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

            • dronedarone

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

            • droperidol

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

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

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

            • drospirenone

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

            • droxidopa

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

            • duloxetine

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

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

            • edoxaban

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

            • elagolix

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

            • eletriptan

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

            • eltrombopag

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

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • enalapril

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

            • ephedrine

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

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

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

            • enoxaparin

              enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI

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

            • epinephrine

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

            • ephedrine

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

            • epinephrine

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

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

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

            • epinephrine inhaled

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

            • epinephrine racemic

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

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

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

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

            • epoprostenol

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

            • esketamine intranasal

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

            • erlotinib

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

            • eprosartan

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

              aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

            • eptifibatide

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

            • escitalopram

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

            • esketamine intranasal

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

            • escitalopram

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

            • esketamine intranasal

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

            • esmolol

              aspirin decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

            • estazolam

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

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

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

            • ethacrynic acid

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

            • ethanol

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

            • estradiol

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

            • ethanol

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

            • estradiol vaginal

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

            • estrogens conjugated synthetic

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

            • estropipate

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

            • ethanol

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

            • ethinylestradiol

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

            • ethotoin

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

            • etodolac

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

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

            • etomidate

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

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

            • etonogestrel

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

            • fedratinib

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

            • etravirine

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

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

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

            • felodipine

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

            • fenbufen

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

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

            • fenfluramine

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

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

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

            • fennel

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

            • fexinidazole

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

            • fenoprofen

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

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

            • fesoterodine

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

            • feverfew

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

            • fish oil

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

            • fish oil triglycerides

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

            • flibanserin

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

            • flibanserin

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

            • fludrocortisone

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

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

            • fluoxetine

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

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

            • fluphenazine

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

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

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

            • flurazepam

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

            • flurazepam

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

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

            • flurbiprofen

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

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

            • fluvoxamine

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

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

            • fondaparinux

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

            • formoterol

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

            • formoterol

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

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

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

            • forskolin

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

            • fosamprenavir

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

            • fosinopril

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

            • furosemide

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

            • gabapentin

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

            • 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.

            • garlic

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

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glecaprevir/pibrentasvir

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

            • glimepiride

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

            • glipizide

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

            • glyburide

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

            • green tea

              green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.

              green tea increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.

            • griseofulvin

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

            • guselkumab

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

            • haloperidol

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

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

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

            • gotu kola

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

            • hydromorphone

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

            • guanfacine

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

            • haloperidol

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

            • hawthorn

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

            • hemin

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

            • heparin

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

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

            • hops

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

            • horse chestnut seed

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

            • hyaluronidase

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

            • hydralazine

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

            • hydrochlorothiazide

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

            • hydrocortisone

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

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

            • hydromorphone

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

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

            • hydroxyzine

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

            • ibrutinib

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

            • hydroxyprogesterone caproate

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

            • hydroxyzine

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

            • hydroxyzine

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

            • ibuprofen

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

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

            • ibuprofen IV

              aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.

              aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.

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

            • icosapent

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

            • ifosfamide

              butalbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.

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

            • iloperidone

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

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

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

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

            • imatinib

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

            • imipramine

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

            • imipramine

              butalbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

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

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

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

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

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

            • indapamide

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

            • indinavir

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

            • indomethacin

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

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

            • insulin aspart

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

            • insulin aspart protamine/insulin aspart

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

            • insulin degludec

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

            • insulin degludec/insulin aspart

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

            • insulin detemir

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

            • insulin glargine

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

            • insulin glulisine

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

            • insulin inhaled

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

            • insulin isophane human/insulin regular human

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

            • insulin lispro

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

            • insulin lispro protamine/insulin lispro

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

            • insulin NPH

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

            • insulin regular human

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

            • irbesartan

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

              aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

            • isoniazid

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

            • isoproterenol

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

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

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

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

            • ixabepilone

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

            • ketotifen, ophthalmic

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

            • ketoprofen

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

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

            • ketamine

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

            • kava

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

            • ketamine

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

            • ketoconazole

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

            • ketorolac

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

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

            • ketorolac intranasal

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

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

            • ketotifen, ophthalmic

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

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

            • labetalol

              aspirin decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

            • lasmiditan

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

            • latanoprost

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

            • lapatinib

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

            • lasmiditan

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

            • latanoprostene bunod ophthalmic

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

            • lemborexant

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

            • letermovir

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

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

            • levalbuterol

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

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

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

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

            • levamlodipine

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

            • levorphanol

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

            • levomilnacipran

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

            • levorphanol

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

            • 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

              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. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

            • 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.

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

            • lisinopril

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

            • lofepramine

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

            • lithium

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

            • lofepramine

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

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

            • lofexidine

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

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

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

            • lopinavir

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

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

            • loprazolam

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

            • loprazolam

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

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

            • loratadine

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

            • lorazepam

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

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

            • lorazepam

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

            • lormetazepam

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

            • lorcaserin

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

            • lormetazepam

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

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

            • lornoxicam

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

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

            • losartan

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

              aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

            • loxapine

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

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

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

            • loxapine inhaled

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

              codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.

              butalbital and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lumefantrine

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

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

            • maprotiline

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

            • lurasidone

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

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

            • maprotiline

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

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

            • maraviroc

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

            • marijuana

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

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

            • marijuana

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

            • melatonin

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

            • meclofenamate

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

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

            • mefenamic acid

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

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

            • melatonin

              melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.

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

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

            • meloxicam

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

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

            • meperidine

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

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

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

            • meprobamate

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

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

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

            • mesalamine

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

            • metaproterenol

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

            • mestranol

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

            • metaproterenol

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

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

            • metaproterenol

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

            • methadone

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

            • methamphetamine

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

            • methazolamide

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

            • metaxalone

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

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

            • methadone

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

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

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

            • methamphetamine

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

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

            • methocarbamol

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

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

            • methotrexate

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

            • methyclothiazide

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

            • methylenedioxymethamphetamine

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

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

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

            • methylphenidate

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

            • methylprednisolone

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

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

            • metolazone

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

            • metoprolol

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

            • mexiletine

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

            • midazolam

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

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

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

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

            • metoprolol

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

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

            • midodrine

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

            • midazolam intranasal

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

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

            • midodrine

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

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

            • milnacipran

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

            • mirabegron

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

            • mirtazapine

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

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

            • mirtazapine

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

            • modafinil

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

            • mistletoe

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

            • modafinil

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

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

            • moexipril

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

            • morphine

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

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

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

            • motherwort

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

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

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

            • moxisylyte

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

            • moxonidine

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

            • moxonidine

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

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

            • mycophenolate

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

            • nabilone

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

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

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

            • nabumetone

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

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

            • nalbuphine

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

            • nadolol

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

              aspirin decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • nafcillin

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

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

            • nalbuphine

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

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

            • naproxen

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

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

            • nateglinide

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

            • nebivolol

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

              aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • nefazodone

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

            • nelfinavir

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

            • nettle

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

            • nicardipine

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

            • nilotinib

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

            • nisoldipine

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

            • nitazoxanide

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

            • nitroglycerin rectal

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

            • nitroglycerin sublingual

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

            • norepinephrine

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

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

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

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

            • nortriptyline

              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.

            • olanzapine

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

            • olanzapine

              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.

            • 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.

            • olmesartan

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

              aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

            • omega 3 carboxylic acids

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

            • omega 3 fatty acids

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

            • omeprazole

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

            • opium tincture

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

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

            • opium tincture

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

            • oxazepam

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

            • orphenadrine

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

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

            • osilodrostat

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

            • ospemifene

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

            • oxacillin

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

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

            • oxaprozin

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

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

            • oxazepam

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

            • oxazepam

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

            • oxycodone

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

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

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

            • oxymorphone

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

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

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

            • paliperidone

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

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

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

            • panax ginseng

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

            • papaveretum

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

            • papaveretum

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

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

            • papaverine

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

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

            • parecoxib

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

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

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

            • paroxetine

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

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

            • passion flower

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

            • pau d'arco

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

            • pazopanib

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

            • pefloxacin

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

            • pegaspargase

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

            • peginterferon alfa 2b

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

            • pegvisomant

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

            • penbutolol

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

              aspirin decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • penicillin G aqueous

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

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

            • pentazocine

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

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

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

            • pentobarbital

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

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

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

            • perampanel

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

            • perphenazine

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

            • perindopril

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

            • perphenazine

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

            • perphenazine

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

            • phendimetrazine

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

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

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

            • phenindione

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

            • phenobarbital

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

            • phenobarbital

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

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

            • phenoxybenzamine

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

            • phentermine

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

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

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

            • phentolamine

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

            • phenylephrine

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

            • phenylephrine

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

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

            • phenylephrine PO

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

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

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

            • phenytoin

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

            • pholcodine

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

            • pholcodine

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

            • pholcodine

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

            • phytoestrogens

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

            • pimozide

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

              butalbital and pimozide both increase sedation. Use Caution/Monitor.

              pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pindolol

              pindolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              butalbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • pirbuterol

              pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

            • pirbuterol

              aspirin increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              butalbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • piroxicam

              aspirin and piroxicam both increase anticoagulation. Use Caution/Monitor.

              aspirin and piroxicam both increase serum potassium. Use Caution/Monitor.

            • pitolisant

              butalbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

            • pivmecillinam

              pivmecillinam, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              pivmecillinam, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • polatuzumab vedotin

              butalbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

            • potassium acid phosphate

              aspirin and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium chloride

              aspirin and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium citrate

              aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

            • potassium iodide

              potassium iodide and aspirin both increase serum potassium. Use Caution/Monitor.

            • prasugrel

              aspirin, prasugrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • prazosin

              aspirin decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • prednisolone

              butalbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • prednisone

              aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

              butalbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pregabalin

              pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

              pregabalin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • prochlorperazine

              prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • promethazine

              promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • propranolol

              propranolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • primidone

              primidone and codeine both increase sedation. Use Caution/Monitor.

              butalbital and primidone both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              butalbital and prochlorperazine both increase sedation. Use Caution/Monitor.

              codeine and prochlorperazine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and butalbital both increase sedation. Use Caution/Monitor.

              promethazine and codeine both increase sedation. Use Caution/Monitor.

            • propafenone

              butalbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.

            • propofol

              propofol and codeine both increase sedation. Use Caution/Monitor.

            • propofol

              propofol and butalbital both increase sedation. Use Caution/Monitor.

            • propranolol

              butalbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • propylhexedrine

              caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.

              codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protamine

              protamine and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • protriptyline

              protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              butalbital and protriptyline both increase sedation. Use Caution/Monitor.

              codeine and protriptyline both increase sedation. Use Caution/Monitor.

            • quazepam

              quazepam and codeine both increase sedation. Use Caution/Monitor.

              butalbital and quazepam both increase sedation. Use Caution/Monitor.

              quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quetiapine

              butalbital and quetiapine both increase sedation. Use Caution/Monitor.

              codeine and quetiapine both increase sedation. Use Caution/Monitor.

              quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinapril

              quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

            • rasagiline

              rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

            • quinidine

              quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

              butalbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ramelteon

              butalbital and ramelteon both increase sedation. Use Caution/Monitor.

              codeine and ramelteon both increase sedation. Use Caution/Monitor.

              butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • ramipril

              ramipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

            • reishi

              aspirin and reishi both increase anticoagulation. Use Caution/Monitor.

            • remimazolam

              remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

              remimazolam, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • repaglinide

              butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • reteplase

              aspirin, reteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • ribociclib

              ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin decreases levels of butalbital by increasing metabolism. Use Caution/Monitor.

            • risperidone

              codeine and risperidone both increase sedation. Use Caution/Monitor.

              butalbital and risperidone both increase sedation. Use Caution/Monitor.

              risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ritonavir

              ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

              butalbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

            • rivaroxaban

              aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

            • rivastigmine

              rivastigmine increases toxicity of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

            • rolapitant

              rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • sacubitril/valsartan

              sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • salicylates (non-asa)

              aspirin and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.

              aspirin and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

            • salmeterol

              butalbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              aspirin increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

            • salmeterol

              codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • scullcap

              scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salsalate

              aspirin and salsalate both increase anticoagulation. Use Caution/Monitor.

              aspirin and salsalate both increase serum potassium. Use Caution/Monitor.

            • saquinavir

              butalbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saw palmetto

              saw palmetto increases toxicity of aspirin by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

            • scullcap

              codeine and scullcap both increase sedation. Use Caution/Monitor.

              butalbital and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital and secobarbital both increase sedation. Use Caution/Monitor.

              secobarbital and codeine both increase sedation. Use Caution/Monitor.

            • selegiline

              selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

              selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

            • selumetinib

              aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

            • shepherd's purse

              shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sertraline

              sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • Siberian ginseng

              aspirin and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.

            • shepherd's purse

              butalbital and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sertraline

              sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • sevoflurane

              sevoflurane and codeine both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              codeine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sildenafil

              butalbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • silodosin

              aspirin decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • solifenacin

              butalbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • solriamfetol

              caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • sorafenib

              butalbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

            • sotalol

              sotalol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              butalbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • spironolactone

              spironolactone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

              aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

            • 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.

            • succinylcholine

              aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.

            • sufentanil

              sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sufentanil

              codeine and sufentanil both increase sedation. Use Caution/Monitor.

              butalbital and sufentanil both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              butalbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.

            • sulfamethoxazole

              aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

            • sulfasalazine

              aspirin and sulfasalazine both increase anticoagulation. Use Caution/Monitor.

              aspirin and sulfasalazine both increase serum potassium. Use Caution/Monitor.

            • sulindac

              aspirin and sulindac both increase anticoagulation. Use Caution/Monitor.

              aspirin and sulindac both increase serum potassium. Use Caution/Monitor.

            • suvorexant

              suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • sunitinib

              butalbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tacrolimus

              butalbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tadalafil

              butalbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tafluprost

              tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • tapentadol

              codeine and tapentadol both increase sedation. Use Caution/Monitor.

              butalbital and tapentadol both increase sedation. Use Caution/Monitor.

              tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • telmisartan

              telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • temazepam

              temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • temazepam

              butalbital and temazepam both increase sedation. Use Caution/Monitor.

              temazepam and codeine both increase sedation. Use Caution/Monitor.

            • temocillin

              temocillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              temocillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • temsirolimus

              butalbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tenecteplase

              aspirin, tenecteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • terazosin

              aspirin decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • terbinafine

              terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

            • terbinafine

              butalbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • terbutaline

              terbutaline and caffeine both decrease sedation. Use Caution/Monitor.

              codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              aspirin increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • teriflunomide

              teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • thalidomide

              thalidomide increases effects of butalbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

            • thioridazine

              thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thiothixene

              thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ticagrelor

              aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.

            • thioridazine

              thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

              codeine and thioridazine both increase sedation. Use Caution/Monitor.

            • theophylline

              butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              butalbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • thioridazine

              butalbital and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              codeine and thiothixene both increase sedation. Use Caution/Monitor.

              butalbital and thiothixene both increase sedation. Use Caution/Monitor.

            • ticarcillin

              ticarcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              ticarcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • ticlopidine

              ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • timolol

              timolol and aspirin both increase serum potassium. Use Caution/Monitor.

              butalbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

              aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • tinidazole

              butalbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tirofiban

              aspirin, tirofiban. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • tipranavir

              butalbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tobramycin inhaled

              tobramycin inhaled and aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolazamide

              aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolbutamide

              aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolfenamic acid

              aspirin and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.

              aspirin and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              aspirin and tolmetin both increase anticoagulation. Use Caution/Monitor.

              aspirin and tolmetin both increase serum potassium. Use Caution/Monitor.

            • tolterodine

              butalbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolvaptan

              aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • topiramate

              topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • torsemide

              aspirin increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tramadol

              tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tramadol

              butalbital and tramadol both increase sedation. Use Caution/Monitor.

              codeine and tramadol both increase sedation. Use Caution/Monitor.

            • trandolapril

              trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.

            • tranylcypromine

              tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

            • travoprost ophthalmic

              travoprost ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • trazodone

              trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              butalbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              butalbital and trazodone both increase sedation. Use Caution/Monitor.

              trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trazodone

              codeine and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.

            • triamcinolone acetonide injectable suspension

              butalbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triamterene

              triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

            • triazolam

              butalbital and triazolam both increase sedation. Use Caution/Monitor.

              butalbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              triazolam and codeine both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and codeine both increase sedation. Use Caution/Monitor.

              triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital and triclofos both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              butalbital and trifluoperazine both increase sedation. Use Caution/Monitor.

              codeine and trifluoperazine both increase sedation. Use Caution/Monitor.

              trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trimipramine

              butalbital and trimipramine both increase sedation. Use Caution/Monitor.

              codeine and trimipramine both increase sedation. Use Caution/Monitor.

              trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triprolidine

              triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              triprolidine and butalbital both increase sedation. Use Caution/Monitor.

              triprolidine and codeine both increase sedation. Use Caution/Monitor.

            • valproic acid

              aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

            • xylometazoline

              caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

            • valsartan

              valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • vardenafil

              butalbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • venlafaxine

              venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • verapamil

              butalbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voclosporin

              voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • vorapaxar

              aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

              aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

            • vortioxetine

              aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

            • warfarin

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              warfarin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. The need for simultaneous use of low-dose aspirin and warfarin are common for patients with cardiovascular disease; monitor closely.

              butalbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • xylometazoline

              codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              butalbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              caffeine and yohimbine both decrease sedation. Use Caution/Monitor.

            • zanubrutinib

              aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

            • yohimbine

              butalbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              butalbital and ziconotide both increase sedation. Use Caution/Monitor.

              codeine and ziconotide both increase sedation. Use Caution/Monitor.

              ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziprasidone

              butalbital and ziprasidone both increase sedation. Use Caution/Monitor.

              codeine and ziprasidone both increase sedation. Use Caution/Monitor.

              ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • zotepine

              aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

              butalbital and zotepine both increase sedation. Use Caution/Monitor.

              codeine and zotepine both increase sedation. Use Caution/Monitor.

            Minor (267)

            • aceclofenac

              aceclofenac will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              acemetacin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acetazolamide

              acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • acyclovir

              aspirin will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • adenosine

              caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • alendronate

              aspirin, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

            • 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.

            • aluminum hydroxide

              aluminum hydroxide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • amantadine

              amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

            • American ginseng

              American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

            • amikacin

              aspirin increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • aminohippurate sodium

              aspirin will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • amitriptyline

              butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • amobarbital

              amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • amoxapine

              butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • amphotericin B deoxycholate

              butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • anamu

              aspirin and anamu both increase anticoagulation. Minor/Significance Unknown.

            • antipyrine

              butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • armodafinil

              butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ascorbic acid

              aspirin decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.

              ascorbic acid increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

              ascorbic acid will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

            • butabarbital

              butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • asenapine

              butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

              asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • balsalazide

              aspirin will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ashwagandha

              ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bismuth subsalicylate

              bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • atazanavir

              butalbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • bosentan

              butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • brinzolamide

              brinzolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • bumetanide

              aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

            • buprenorphine subdermal implant

              butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

            • butalbital

              butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • caffeine

              butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • calcium acetate

              caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

            • calcium carbonate

              calcium carbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

              caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

            • calcium chloride

              caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

            • cefadroxil

              cefadroxil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • calcium citrate

              caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

            • calcium gluconate

              caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

            • carbamazepine

              carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefepime

              cefepime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefixime

              cefixime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefprozil

              cefprozil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftazidime

              ceftazidime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftibuten

              ceftibuten will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cevimeline

              butalbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • chloramphenicol

              chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.

              butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpromazine

              butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

            • chlorpropamide

              aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • chlorthalidone

              chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • choline magnesium trisalicylate

              aspirin will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chromium

              aspirin increases levels of chromium by unspecified interaction mechanism. Minor/Significance Unknown.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • clarithromycin

              butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

            • clotrimazole

              clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • clomipramine

              butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • clotrimazole

              butalbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • cocaine

              butalbital will decrease the level or effect of cocaine by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

            • cortisone

              cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • creatine

              creatine, aspirin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

            • cyanocobalamin

              aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • cyclopenthiazide

              cyclopenthiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • danshen

              aspirin and danshen both increase anticoagulation. Minor/Significance Unknown.

            • dapsone

              butalbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • deflazacort

              deflazacort decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • desipramine

              butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • devil's claw

              aspirin and devil's claw both increase anticoagulation. Minor/Significance Unknown.

            • dexamethasone

              dexamethasone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • dextroamphetamine

              dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

            • diclofenac

              butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              aspirin will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diclofenac topical

              diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

            • disopyramide

              butalbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • diflunisal

              aspirin will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diltiazem

              diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • docetaxel

              butalbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              butalbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dosulepin

              butalbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • doxepin

              butalbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • dutasteride

              butalbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • efavirenz

              butalbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eplerenone

              butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              aspirin decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • erythromycin base

              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

              erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • erythromycin ethylsuccinate

              butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

            • erythromycin lactobionate

              butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

            • erythromycin stearate

              butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

            • ethanol

              ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ethosuximide

              ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

            • etodolac

              aspirin will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • eucalyptus

              butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

              codeine and eucalyptus both increase sedation. Minor/Significance Unknown.

              butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.

            • fenbufen

              aspirin will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fluconazole

              fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • fenoprofen

              aspirin will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • feverfew

              aspirin decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

            • finasteride

              butalbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • fluoxetine

              fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • fluconazole

              butalbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • flurbiprofen

              aspirin will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • folic acid

              aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • frovatriptan

              butalbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • furosemide

              aspirin decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • galantamine

              butalbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ganciclovir

              aspirin will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • gentamicin

              aspirin increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • glimepiride

              aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • glipizide

              aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • glyburide

              aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • grapefruit

              grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • griseofulvin

              butalbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • guarana

              guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

            • haloperidol

              haloperidol, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

            • hydrochlorothiazide

              hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • ibuprofen

              butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ibuprofen IV

              butalbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • imidapril

              aspirin decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • imatinib

              imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

              butalbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • imipramine

              butalbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • indapamide

              indapamide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indomethacin

              aspirin will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • isoniazid

              isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • itraconazole

              itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • ketoconazole

              ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • ketoprofen

              aspirin will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac

              aspirin will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac intranasal

              aspirin will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • L-methylfolate

              aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • 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.

            • levothyroxine

              butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

            • linezolid

              linezolid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • liothyronine

              butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

            • lofepramine

              butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • lornoxicam

              aspirin will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • losartan

              butalbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • maprotiline

              butalbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • maraviroc

              maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • meclofenamate

              aspirin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mefenamic acid

              aspirin will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meloxicam

              aspirin will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              butalbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • mesalamine

              aspirin will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methazolamide

              methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

            • methsuximide

              methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

            • methyclothiazide

              methyclothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • metolazone

              metolazone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mexiletine

              mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

            • nabumetone

              aspirin will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • naproxen

              aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • neomycin PO

              aspirin increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • nettle

              nettle increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

            • nifedipine

              butalbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • nimodipine

              butalbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              butalbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • noni juice

              aspirin and noni juice both increase serum potassium. Minor/Significance Unknown.

            • nortriptyline

              butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • ofloxacin

              ofloxacin, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

            • oxaprozin

              aspirin will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • oxybutynin

              butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              butalbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              butalbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              aspirin will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • paromomycin

              aspirin increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • 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.

            • penicillin VK

              penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

            • pentazocine

              aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

            • phenelzine

              phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • phenobarbital

              phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • pimozide

              butalbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

              butalbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pipemidic acid

              pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • piperacillin

              piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

            • piroxicam

              aspirin will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              butalbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • posaconazole

              butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • prednisolone

              prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • prednisone

              prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • propafenone

              propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • protriptyline

              butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • quinacrine

              quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • quinine

              butalbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rabeprazole

              butalbital will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramelteon

              butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • rifampin

              rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • riluzole

              butalbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • rose hips

              aspirin decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.

              rose hips will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

              rose hips increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

            • sage

              sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

              codeine and sage both increase sedation. Minor/Significance Unknown.

              butalbital and sage both increase sedation. Minor/Significance Unknown.

            • salicylates (non-asa)

              aspirin will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • salsalate

              aspirin will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • saxagliptin

              butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sertraline

              sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • selegiline transdermal

              selegiline transdermal increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • Siberian ginseng

              Siberian ginseng increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • smoking

              smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • sodium bicarbonate

              sodium bicarbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • sodium citrate/citric acid

              sodium citrate/citric acid, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • stiripentol

              aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • streptomycin

              aspirin increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • sufentanil

              butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfadiazine

              aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulfamethoxazole

              butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • sulfasalazine

              aspirin will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulfisoxazole

              aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulindac

              aspirin will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tamoxifen

              butalbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • teniposide

              aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

            • thiamine

              caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

            • thioridazine

              thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

              thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown.

            • thyroid desiccated

              butalbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

            • tiludronate

              aspirin decreases levels of tiludronate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • tipranavir

              tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tibolone

              butalbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • tobacco use

              tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • tobramycin

              aspirin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • tolazamide

              aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • tolbutamide

              butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • tolfenamic acid

              aspirin will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • topiramate

              butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • tolmetin

              aspirin will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tranylcypromine

              tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

            • trazodone

              butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • triamterene

              triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.

              aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

            • trimipramine

              butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • valganciclovir

              aspirin will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • vancomycin

              aspirin increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

            • venlafaxine

              venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • verapamil

              verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

              verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • vinblastine

              butalbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • voriconazole

              voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • vincristine

              butalbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vincristine liposomal

              butalbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vinorelbine

              butalbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • voriconazole

              butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • warfarin

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • willow bark

              aspirin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              willow bark increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

            • yerba mate

              yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

            • zafirlukast

              aspirin increases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

            • zaleplon

              butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ziconotide

              ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

            • zileuton

              zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ziprasidone

              butalbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            Previous
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            Adverse Effects

            >10%

            Codeine

            • Constipation
            • Drowsiness

            1-10%

            Codeine

            • Hypotension, tachycardia or bradycardia, confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, rash, urticaria, anorexia, nausea, vomiting, xerostomia, ureteral spasm, urination decreased, LFT's increased, weakness, blurred vision, dyspnea, histamine-release

            Frequency Not Defined

            Butalbital

            • Drowsiness, sedation
            • Lightheadedness, dizziness
            • Shortness of breath
            • Nausea, vomiting
            • Abdominal pain
            • Intoxicated feeling

            Aspirin

            • Stomach pain
            • Heartburn
            • Nausea, vomiting
            • Dyspepsia
            • Tinnitus (high or chronic dose)
            • Rash
            • Urticaria

            Caffeine

            • Insomnia, restlessness
            • Nervousness, irritability
            • Tremor
            • Tinnitus
            • Nausea, vomiting
            • Diarrhea
            • Tachycardia
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            Warnings

            Black Box Warnings

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
            • Healthcare providers are strongly encouraged to:
              • Complete a REMS-compliant education program
              • Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
              • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
              • Consider other tools to improve patient, household, and community safety

            Addiction and abuse

            • Therapy exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death; assess patient’s risk before prescribing and monitor regularly for these behaviors and conditions

            Life threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur; monitor closely, especially upon initiation or following a dose increase

            Accidental ingestion

            • Accidental ingestion of drug, especially by children, can result in fatal overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Postoperative pain in children

            • Deaths have occurred in children with obstructive sleep apnea who receive codeine for postoperative pain following tonsillectomy and/or adenoidectomy
            • Codeine is converted to morphine by the liver; these children had evidence of being ultra-rapid metabolizers (via CYP2D6) of codeine, which is an inherited (genetic) ability that causes codeine to be converted rapidly into life-threatening or fatal amounts of morphine (see Pharmacology)
            • Contraindicated in children younger than 12 years ; life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to active metabolite morphine; children < 12 years appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of codeine
            • Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose

            Coadministration with benzodiazepines

            • Risks from concomitant use with benzodiazepines or other CNS depressants; concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing of this drug combination and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

            Interactions with drugs affecting cytochrome P450 isoenzymes

            • Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine sulfate requires careful consideration of effects on parent drug, codeine, and active metabolite, morphine

            Contraindications

            Hypersensitivity

            Children <12 years (increased risk of death from opioid)

            Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy

            Children <16 years because of potential for Reye syndrome

            Postoperative use in children following tonsillectomy and/or adenoidectomy (see Black Box Warnings)

            Bronchospastic reaction to aspirin

            Syndrome of asthma, rhinitis, and nasal polyps

            Significant respiratory depression

            Peptic ulcer disease

            Known allergy to NSAIDs

            Within 14 days of taking MAOIs

            Hemophilia

            Repeated administration in patients with anemia, cardiovascular, pulmonary, or renal disease

            Porphyria

            Cautions

            Gastrointestinal bleeding; particular caution in patients with history of GI bleed, alcoholism, or bleeding disorders

            Avoid driving car or operating machinery

            Reye syndrome may occur in children because of aspirin component; do not use for chickenpox or flu symptoms

            Avoid in severe renal impairment (ie, CrCl <10 mL/min)

            Avoid use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms

            May increase respiratory depressant effects; caution with head injury, COPD, or other conditions with decreased respiratory drive

            As butalbital, aspirin, caffeine, and codeine phosphate drug dosage forms contain butalbital and codeine, they expose users to the risks of addiction, abuse, and misuse; assess each patient’s risk for addiction, abuse, or misuse prior to prescribing therapy, and monitor all patients receiving drug for development of addiction behaviors and conditions

            Effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex; use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with butalbital, acetaminophen, caffeine, and codeine phosphate combination require careful consideration of effects on codeine and active metabolite, morphine

            Codeine may cause tolerance/dependency; assess each patient’s risk for addiction, abuse, or misuse prior to prescribing drug, and monitor all patients for development of behaviors and conditions associated with addiction

            Life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to active metabolite morphine; children <12 years and pediatric patients <18 years, following tonsillectomy and/or adenoidectomy, appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of codeine

            Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

            Avoid use of drug combination in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose

            At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine; breastfeeding is not recommended during treatment

            Serious, life-threatening, or fatal respiratory depression may occur; monitor closely, especially upon initiation or following a dose increase

            Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain

            Low doses of aspirin can inhibit platelet function leading to an increase in bleeding time; this can adversely affect patients with inherited (i.e. hemophilia) or acquired (i.e. liver disease or vitamin K deficiency) bleeding disorders; aspirin is contraindicated in patients with hemophilia

            Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of risk of Reye syndrome with concomitant use of aspirin in certain viral illnesses; aspirin administered pre-operatively may prolong bleeding time

            Adrenal Insufficiency may occur; if diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid

            In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), butalbital, aspirin, caffeine, and codeine phosphate drug combination may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor for sedation and respiratory depression

            Opioids may obscure clinical course in patient with a head injury; avoid use of butalbital, aspirin, caffeine, and codeine phosphate drug combination in patients with impaired consciousness or coma

            Butalbital, aspirin, caffeine, and codeine phosphate drug combination may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs; monitor these patients for signs of hypotension after initiating or titrating dosage

            The codeine in butalbital, aspirin, caffeine, and codeine phosphate drug combination may increase frequency of seizures in patients with seizure disorders and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during butalbital, aspirin, caffeine, and codeine phosphate drug combination

            Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; to reduce risk of respiratory depression, proper dosing and titration are essential; due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for emergency treatment of opioid overdose

            Profound sedation, respiratory depression, coma, and death may result from concomitant with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concomitant use with benzodiazepine warranted, consider prescribing naloxone for emergency treatment of opioid overdose

            Monoamine oxidase inhibitors (MAOIs) may potentiate effects of morphine, codeine’s active metabolite, including respiratory depression, coma, and confusion; drug should not be used in patients taking MAOIs or within 14 days of stopping such treatment

            Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding.

            Drug reaction with eosinophilia and systemic symptoms

            • Drug Reaction reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
            • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
            • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
            • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately

            Respiratory depression

            • Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death; management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on patient’s clinical status
            • Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids
            • While serious, life-threatening, or fatal respiratory depression can occur at any time, the risk is greatest during initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within first 24-72 hours of initiating therapy with and following dosage increases of drug combination
            • To reduce the risk of respiratory depression, proper dosing and titration are essential; overestimating the dosage when converting patients from another opioid product can result in a fatal overdose with the first dose
            • Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose

            Patient access to naloxone for emergency treatment of opioid overdose

            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
            • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage

            Withdrawal seizures reported in two-day-old male infant whose mother had taken a butalbital-containing drug during the last 2 months of pregnancy; butalbital was found in infant’s serum; the infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms

            Fetal toxicity

            • Use of NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
            • Because of these risks, limit dose and duration of drug combination between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy
            • Use of NSAIDs, including drug combination, at about 30 weeks gestation or later in pregnancy increases risk of premature closure of the fetal ductus arteriosus
            • Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment
            • If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit use to the lowest effective dose and shortest duration possible; if drug combination treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue drug use and follow up according to clinical practice
            • Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive

            Animal data

            • Based on animal data, prostaglandins have been shown to have important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors such as aspirin, resulted in increased pre- and post-implantation loss
            • Prostaglandins also have been shown to have an important role in fetal kidney development; in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses

            Labor or delivery

            • Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Lactation

            Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants; in women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent

            There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment

            Aspirin, caffeine, and barbiturates are excreted in breast milk in small amounts, but the significance of their effects on nursing infants not known; because of potential for serious adverse reactions in nursing infants from drug combination, a decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to the mother

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Butalbital: Barbiturate; elicits generalized CNS depressant effects

            Aspirin: Acts on hypothalamus to produce antipyresis; anti-inflammatory properties attributed to prostaglandin synthetase inhibition resulting in decreased formation of thromboxane A2

            Caffeine: Vasoconstrictive properties of cerebral blood vessels may be helpful when treating headaches

            Codeine: Opioid agonist; analgesia

            Pharmacogenomics

            10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors

            CYP2D6 poor metabolizers may not achieve adequate analgesia

            Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

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            Formulary

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            Tier Description
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.