butalbital/aspirin/caffeine/codeine (Rx)

Tension Headache

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

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

Limitations of Use

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

Dosing Considerations

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

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

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

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

Tension Headache

<16 years: Safety and efficacy not established

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

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

Use caution; barbiturates not recommended in the elderly

Tension Headache

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

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

Contraindicated (14)

• doravirine

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

• fezolinetant

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

• fostemsavir

  butalbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• isavuconazonium sulfate

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

• 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.

• lonafarnib

  butalbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lorlatinib

  butalbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• mavacamten

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

• phenelzine

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

• procarbazine

  procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.

• selegiline transdermal

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

• tranylcypromine

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

• zoliflodacin

  butalbital decreases levels of zoliflodacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Moderate and strong CYP3A4 inducers are predicted to result in decreased plasma concentrations of zoliflodacin and may reduce its efficacy.

Serious (104)

• 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.

• 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.

• atogepant

  butalbital decreases levels of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Modify atogepant dose for episodic migraine if coadministered with a strong or moderate CYP3A4 inducer (see Dosage Modifications). Atogepant is not recommended for patients with chronic migraine if coadministered with a strong or moderate CYP3A4 inducer. .

• atrasentan

  butalbital decreases levels of atrasentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong or moderate CYP3A inducers is expected to decrease atrasentan systemic exposure, which may decrease efficacy. .

• 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.

• benzhydrocodone/acetaminophen

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

• bivalirudin

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

• brexpiprazole

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

• brigatinib

  butalbital decreases levels of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of brigatinib with strong CYP3A4 inducers.

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• buprenorphine, long-acting injection

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

• bupropion

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

• calcium/magnesium/potassium/sodium oxybates

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

• capivasertib

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

• 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.

• dalteparin

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

• daridorexant

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

• deflazacort

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• dipyridamole

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

• dronedarone

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

• givosiran

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

• duloxetine

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

• duvelisib

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

• elacestrant

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

• elinzanetant

  butalbital decreases levels of elinzanetant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of elinzanetant with moderate or strong CYP3A4 inducers.

• enoxaparin

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

• ensartinib

  butalbital decreases levels of ensartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ensartinib with strong or moderate CYP3A inducers may decrease ensartinib exposure.

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

• fentanyl intranasal

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

• fentanyl iontophoretic transdermal system

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

• fentanyl transdermal

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

• fentanyl transmucosal

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

• 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.

• finerenone

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

• fondaparinux

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

• fostamatinib

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

• fruquintinib

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

• ganaxolone

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

• glasdegib

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

• heparin

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

• hydrocodone

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

• imlunestrant

  butalbital decreases levels of imlunestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of imlunestrant with strong CYP3A inducers; if unavoidable, increase imlunestrant dose (see Dosage Modifications).

• infigratinib (DSC)

  butalbital will decrease the level or effect of infigratinib (DSC) 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, butalbital. Other (see comment). Contraindicated. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.

• istradefylline

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

• ivosidenib

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

• larotrectinib

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

• lazertinib

  butalbital decreases levels of lazertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lazertinib with strong or moderate CYP3A4 inducers.

• lefamulin

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

• lemborexant

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

• lenacapavir

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

• leniolisib

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

• lovastatin

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

• lumateperone

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

• lurbinectedin

  butalbital decreases levels of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration due to risk of decreased lurbinectedin exposure and reduced efficacy.

• macimorelin

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

• mestranol

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

• methohexital

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

• methoxyflurane

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

• methylene blue

  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

  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.

• mitapivat

  butalbital decreases levels of mitapivat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternant therapies that are not moderate CYP3A inducers during treatment with mitapivat. If unable to avoid coadministration, monitor Hb and titrate beyond 50 mg BID, if necessary, but do not exceed mitapivat dose of 100 mg BID. .

• 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.

• nerandomilast

  butalbital decreases levels of nerandomilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease systemic exposure of nerandomilast, which may reduce its efficacy.

• neratinib

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

• nirogacestat

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

• olopatadine intranasal

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

• olutasidenib

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

• omaveloxolone

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

• opicapone

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

• orforglipron

  butalbital decreases levels of orforglipron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers significantly decrease plasma levels of orforglipron, reducing effectiveness .

• ozanimod

  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.

• palovarotene

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

• pemigatinib

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

• pexidartinib

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

• phenindione

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

• pimavanserin

  butalbital decreases levels of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pimavanserin with strong or moderate CYP3A4 inducers.

• pirtobrutinib

  butalbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

• pralsetinib

  butalbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• praziquantel

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

• pretomanid

  butalbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

• protamine

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

• quizartinib

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

• ranolazine

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

• regadenoson

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

• relacorilant

  butalbital decreases levels of relacorilant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers can decrease concentrations of relacorilant, which may reduce effectiveness.

Monitor Closely (409)

• abiraterone

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

• acalabrutinib

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

• acebutolol

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

• acetaminophen/phenyltoloxamine

  acetaminophen/phenyltoloxamine and butalbital both increase sedation. Use Caution/Monitor.

• acrivastine

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

• aficamten

  butalbital decreases levels of aficamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate-to-strong CYP3A inducers may decrease aficamten systemic exposure. See Dosage Modifications for recommended aficamten dose.

• albuterol

  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.

• albuterol inhaled

  caffeine, albuterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use may increase risk of cardiovascular adverse effects. Avoid excessive doses of caffeine and monitor BP, HR.

• alfentanil

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

• alfentanil

  alfentanil 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.

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

• amiodarone

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

• amitriptyline

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

• amisulpride

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

• amitriptyline

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

• amlodipine

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

• amoxapine

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

• amphetamine

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

• apomorphine

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

• arformoterol

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

• aprepitant

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

• arformoterol

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

• artemether/lumefantrine

  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

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

• asenapine transdermal

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

• atenolol

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

• atorvastatin

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

• avanafil

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

• avapritinib

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

• azelastine

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

• baclofen

  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

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

• belumosudil

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

• benperidol

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

• benazepril

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

• benperidol

  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.

• betaxolol

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

• brompheniramine

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

• 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.

• brimonidine

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

• brimonidine topical

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

• brivaracetam

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

• brompheniramine

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

• budesonide

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

• buprenorphine

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

• buprenorphine buccal

  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 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.
  
  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.

• butalbital

  butalbital 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. .

• buspirone

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

• butorphanol

  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.

• carbinoxamine

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

• cannabidiol

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

• captopril

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

• carbachol/brimonidine ophthalmic

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

• 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.

• cariprazine

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

• carisoprodol

  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.

• celiprolol

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

• cenobamate

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

• chlordiazepoxide

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

• 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.

• chlorpromazine

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

• chlorzoxazone

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

• cinnarizine

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

• cilostazol

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

• cinacalcet

  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.

• ciprofloxacin

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

• clemastine

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

• clobazam

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

• clomipramine

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

• clomipramine

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

• 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.

• clonidine

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

• 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

  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.
  
  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.

• codeine

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

• colchicine

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

• cyproheptadine

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

• conivaptan

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

• conjugated estrogens

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

• conjugated estrogens, vaginal

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

• cortisone

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

• crinecerfont

  butalbital decreases levels of crinecerfont by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase crinecerfont evening dose 2-fold when coadministered with a moderate CYP3A4 inducer. Do not increase crinecerfont morning dose. .

• cyclobenzaprine

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

• dantrolene

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

• daridorexant

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

• darifenacin

  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.

• dasatinib

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

• deferasirox

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

• desipramine

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

• desloratadine

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

• dexchlorpheniramine

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

• deutetrabenazine

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

• dexamethasone

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

• dexbrompheniramine

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dextroamphetamine

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

• dextromoramide

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

• diamorphine

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

• diazepam

  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.

• diazoxide choline

  diazoxide choline increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Monitor caffeine for adverse effects if coadministered with CYP1A2 inhibitors.

• diazepam buccal

  diazepam buccal and butalbital both increase sedation. Use Caution/Monitor.
  
  diazepam buccal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
  
  butalbital will decrease the level or effect of diazepam buccal 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 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.
  
  diazepam intranasal and butalbital both increase sedation. Use Caution/Monitor.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• difenoxin hcl

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

• diltiazem

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

• dimenhydrinate

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

• diphenhydramine

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

• diphenoxylate hcl

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

• dobutamine

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

• dopamine

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

• dopexamine

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

• dosulepin

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

• doxepin

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

• doxepin

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

• doxycycline

  butalbital decreases levels of doxycycline by increasing metabolism. 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.

• droperidol

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

• droxidopa

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

• 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.

• enasidenib

  enasidenib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Enasidenib (a strong CYP1A2 inhibitor) significantly increases systemic exposure of CYP1A2 substrates. If unable to avoid, dosage reduction of the CYP1A2 substrate may be warranted.

• ephedrine

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

• epinephrine

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

• 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.

• epinephrine racemic

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

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

• esmolol

  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

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

• estradiol

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

• 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.

• eszopiclone

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

• ethanol

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

• ethinylestradiol

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

• etomidate

  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.

• etravirine

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

• felodipine

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

• fenfluramine

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

• fesoterodine

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

• fexinidazole

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

• 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.

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

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

• formoterol

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

• fosamprenavir

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

• fosaprepitant

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

• fosphenytoin

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

• gabapentin

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

• gabapentin enacarbil

  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.
  
  gabapentin enacarbil and butalbital both increase sedation. Use Caution/Monitor.

• ganaxolone

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

• glecaprevir/pibrentasvir

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

• gotu kola

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

• 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.

• 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.
  
  guanfacine and butalbital both increase sedation. 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.
  
  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.

• hydromorphone

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

• hemin

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

• hops

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

• hydrocortisone

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

• hydromorphone

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

• hydroxyprogesterone caproate (DSC)

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

• hydroxyzine

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

• ifosfamide

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

• 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 enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  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.

• isoproterenol

  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.

• 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.

• 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.

• ketotifen, ophthalmic

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

• labetalol

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

• lamotrigine

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

• lapatinib

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

• letermovir

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

• levalbuterol

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

• levamlodipine

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

• levorphanol

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

• levetiracetam

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

• levocetirizine

  levocetirizine and butalbital 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. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

• lidocaine

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

• lisdexamfetamine

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

• lofepramine

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

• lofexidine

  butalbital 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

  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.

• loratadine

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

• lorazepam

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

• lormetazepam

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

• loxapine

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

• lumateperone

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

• marijuana

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

• lumefantrine

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

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

• meclizine

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

• melatonin

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

• meperidine

  butalbital 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.

• mestranol

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

• metaproterenol

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

• metaproterenol

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

• metaxalone

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

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

• methamphetamine

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

• methocarbamol

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

• methotrexate

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

• methsuximide

  methsuximide and butalbital both increase sedation. 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.

• 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.

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

• midazolam intranasal

  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

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

• midodrine

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

• migalastat

  caffeine decreases levels of migalastat by unknown mechanism. Modify Therapy/Monitor Closely. Avoid caffeine ingestion at least 2 hours before and 2 hours after taking migalastat .

• 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.

• modafinil

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

• molindone

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

• morphine

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

• morphine

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nadolol

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

• nalbuphine

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

• nalbuphine

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

• nateglinide

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

• nebivolol

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

• nelfinavir

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

• nicardipine

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

• nilotinib

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

• nisoldipine

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

• nitrous oxide

  nitrous oxide and butalbital both increase sedation. Use Caution/Monitor.

• norepinephrine

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

• norgestrel

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

• nortriptyline

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

• nortriptyline

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

• olanzapine

  butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olanzapine/samidorphan

  butalbital, olanzapine/samidorphan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of diazepam, alcohol, or other CNS acting drugs may potentiate orthostatic hypotension observed with olanzapine. Additive sedation may also occur.

• opium tincture

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

• omeprazole

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

• opium tincture

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

• orphenadrine

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

• osilodrostat

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

• oxazepam

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

• oxycodone

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

• 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.

• paliperidone

  butalbital 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.

• paltusotine

  butalbital decreases levels of paltusotine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inducers may require an increased paltusotine dose. Do not exceed 3-fold dosage prior to concomitant use or 120 mg daily, whichever is less.

• 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.

• papaverine

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

• parecoxib

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

• passion flower

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

• pazopanib

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

• pefloxacin

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

• pentazocine

  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.

• perphenazine

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

• phendimetrazine

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

• phenobarbital

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

• phentermine

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

• phenylephrine

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

• phenylephrine PO

  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

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

• pimozide

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

• pindolol

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

• pirbuterol

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

• pirbuterol

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

• pitolisant

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

• polatuzumab vedotin

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

• prednisolone

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

• prednisone

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

• pregabalin

  pregabalin, 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.
  
  butalbital and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

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

• promethazine

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

• propafenone

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

• propylhexedrine

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

• propofol

  propofol and 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

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

• protriptyline

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

• pyrilamine

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

• quazepam

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

• quazepam

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

• quetiapine

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

• quinidine

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

• rasagiline

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

• ramelteon

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

• remimazolam

  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.

• rifampin

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

• risperidone

  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

  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.

• salmeterol

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

• scopolamine

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

• scullcap

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

• scopolamine intranasal

  scopolamine intranasal and butalbital both increase sedation. Use Caution/Monitor.

• scullcap

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

• selegiline

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

• shepherd's purse

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

• solriamfetol

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

• solifenacin

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

• sorafenib

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

• sotalol

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

• stiripentol

  stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

• sufentanil

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

• tapentadol

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

• sunitinib

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

• tacrolimus

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

• tadalafil

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

• tapentadol

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

• tasimelteon

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

• temazepam

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

• temsirolimus

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

• terbutaline

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

• terbinafine

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

• terbutaline

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

• teriflunomide

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

• tetrabenazine

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

• thalidomide

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

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

• thiothixene

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

• tiagabine

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

• topiramate

  topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• timolol

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

• tinidazole

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

• tipranavir

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

• tizanidine

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

• tolterodine

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

• topiramate

  butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

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

• trazodone

  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.

• 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.

• triazolam

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

• triazolam

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

• triclofos

  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.
  
  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.
  
  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.

• valproic acid

  valproic acid and butalbital both increase sedation. Use Caution/Monitor.

• viloxazine

  viloxazine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Viloxazine (a strong CYP1A2 inhibitor) significantly increases systemic exposure of CYP1A2 substrates. If unable to avoid, dosage reduction of the CYP1A2 substrate may be warranted.

• vardenafil

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

• verapamil

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

• vigabatrin

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

• warfarin

  butalbital will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inducers of these isoenzymes and adjust warfarin dose if needed.

• xylometazoline

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

• yohimbine

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

• zaleplon

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

• ziconotide

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

• ziconotide

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

• ziprasidone

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

• zolpidem

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

• zonisamide

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

• zotepine

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

• zuranolone

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

Minor (140)

• acetazolamide

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

• adenosine

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

• alfentanil

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

• alfuzosin

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

• alosetron

  butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amantadine

  amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amitriptyline

  butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxapine

  butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amphotericin B deoxycholate

  butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• antipyrine

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

• armodafinil

  butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ascorbic acid

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

• butalbital

  butalbital 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.

• ashwagandha

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

• brinzolamide

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

• buprenorphine subdermal implant

  butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• caffeine

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

• calcium acetate

  caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• carbamazepine

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

• celecoxib

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

• cevimeline

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

• chloramphenicol

  chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlorpromazine

  butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• cigarette smoking

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

• cimetidine

  cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• clarithromycin

  butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clotrimazole

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

• clomipramine

  butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clotrimazole

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

• cocaine topical

  butalbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• dapsone

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

• desipramine

  butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• diclofenac

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

• disopyramide

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

• 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.

• erythromycin base

  butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• ethosuximide

  ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• 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.
  
  butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• finasteride

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

• fluconazole

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

• fluconazole

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

• flurbiprofen

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

• frovatriptan

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

• 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.

• ibuprofen

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

• ibuprofen IV

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

• imatinib

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

• 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.

• itraconazole

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

• ketoconazole

  ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• lansoprazole

  butalbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• levoketoconazole

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

• levoketoconazole

  butalbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• levothyroxine

  butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• linezolid

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

• liothyronine

  butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lofepramine

  butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• losartan

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

• meloxicam

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

• methazolamide

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

• methsuximide

  methsuximide decreases effects of butalbital by pharmacodynamic antagonism. 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.

• montelukast

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

• peginterferon alfa 2a

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

• 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.

• nimodipine

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

• nitrendipine

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

• nortriptyline

  butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• 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

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

• pentobarbital

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

• 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.

• piroxicam

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

• posaconazole

  butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• primidone

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

• propafenone

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

• protriptyline

  butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• 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.

• 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

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

• sage

  sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  butalbital and sage both increase sedation. Minor/Significance Unknown.

• saxagliptin

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

• smoking

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

• 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.

• sufentanil

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

• sulfamethoxazole

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

• tamoxifen

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

• thiamine

  caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown.

• thyroid desiccated

  butalbital decreases levels of thyroid desiccated by increasing 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.

• topiramate

  butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• tranylcypromine

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

• trazodone

  butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• trimipramine

  butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• verapamil

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

• vinblastine

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

• vincristine

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

• vincristine liposomal

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

• vinorelbine

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

• voriconazole

  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• yerba mate

  yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• zaleplon

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

• 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.

• abemaciclib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• abiraterone

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

• acalabrutinib

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

• acebutolol

  Monitor Closely (1)butalbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• acetaminophen/phenyltoloxamine

  Monitor Closely (1)acetaminophen/phenyltoloxamine and butalbital both increase sedation. Use Caution/Monitor.

• acetazolamide

  Minor (1)acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• acrivastine

  Monitor Closely (1)acrivastine and butalbital both increase sedation. Use Caution/Monitor.

• adenosine

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

• aficamten

  Monitor Closely (1)butalbital decreases levels of aficamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate-to-strong CYP3A inducers may decrease aficamten systemic exposure. See Dosage Modifications for recommended aficamten dose.

• albuterol

  Monitor Closely (2)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.

• albuterol inhaled

  Monitor Closely (1)caffeine, albuterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use may increase risk of cardiovascular adverse effects. Avoid excessive doses of caffeine and monitor BP, HR.

• alfentanil

  Monitor Closely (2)alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and alfentanil both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

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

• almotriptan

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

• alosetron

  Serious - Use Alternative (1)butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.Minor (2)butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alpelisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.

• alprazolam

  Monitor Closely (3)butalbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  butalbital and alprazolam both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• amantadine

  Minor (1)amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  Minor (1)American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amiodarone

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

• amisulpride

  Monitor Closely (1)amisulpride and butalbital both increase sedation. Use Caution/Monitor.

• amitriptyline

  Monitor Closely (4)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amlodipine

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

• amoxapine

  Monitor Closely (2)amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and amoxapine both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amphetamine

  Monitor Closely (2)butalbital increases and amphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and amphetamine both decrease sedation. Use Caution/Monitor.

• amphotericin B deoxycholate

  Minor (1)butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• antipyrine

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

• antithrombin alfa

  Serious - Use Alternative (1)butalbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

• antithrombin III

  Serious - Use Alternative (1)butalbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

• apomorphine

  Monitor Closely (1)butalbital and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

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

• arformoterol

  Monitor Closely (2)butalbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and caffeine both decrease sedation. Use Caution/Monitor.

• argatroban

  Serious - Use Alternative (1)butalbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

• aripiprazole

  Monitor Closely (3)aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and aripiprazole both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• armodafinil

  Monitor Closely (2)butalbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil and caffeine both decrease sedation. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

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

• ascorbic acid

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

• asenapine

  Monitor Closely (1)asenapine and butalbital both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and butalbital both increase sedation. Use Caution/Monitor.

• ashwagandha

  Minor (1)ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atazanavir

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

• atenolol

  Monitor Closely (1)butalbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• atogepant

  Serious - Use Alternative (1)butalbital decreases levels of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Modify atogepant dose for episodic migraine if coadministered with a strong or moderate CYP3A4 inducer (see Dosage Modifications). Atogepant is not recommended for patients with chronic migraine if coadministered with a strong or moderate CYP3A4 inducer. .

• atorvastatin

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

• atrasentan

  Serious - Use Alternative (1)butalbital decreases levels of atrasentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong or moderate CYP3A inducers is expected to decrease atrasentan systemic exposure, which may decrease efficacy. .

• avanafil

  Monitor Closely (1)butalbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness

• avapritinib

  Monitor Closely (1)avapritinib and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• azelastine

  Monitor Closely (2)azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  azelastine and butalbital both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)butalbital and baclofen both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

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

• belladonna and opium

  Monitor Closely (2)butalbital and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belumosudil

  Monitor Closely (1)butalbital will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.

• bemiparin

  Serious - Use Alternative (1)butalbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

• benazepril

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

• benperidol

  Monitor Closely (2)butalbital and benperidol both increase sedation. Use Caution/Monitor.
  
  benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (2)benzhydrocodone/acetaminophen, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  Monitor Closely (2)butalbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.

• betaxolol

  Monitor Closely (1)butalbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bisoprolol

  Monitor Closely (1)butalbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bivalirudin

  Serious - Use Alternative (1)butalbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

• bortezomib

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

• bosentan

  Minor (2)butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brexanolone

  Monitor Closely (1)brexanolone, butalbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Serious - Use Alternative (1)brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brigatinib

  Serious - Use Alternative (1)butalbital decreases levels of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of brigatinib with strong CYP3A4 inducers.

• brimonidine

  Monitor Closely (1)brimonidine and butalbital both increase sedation. Use Caution/Monitor.

• brimonidine topical

  Monitor Closely (1)brimonidine topical and butalbital both increase sedation. Use Caution/Monitor.

• brinzolamide

  Minor (1)brinzolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• brivaracetam

  Monitor Closely (1)brivaracetam and butalbital both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (2)brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  brompheniramine and butalbital both increase sedation. Use Caution/Monitor.

• budesonide

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

• buprenorphine

  Monitor Closely (1)butalbital and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (2)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 subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateMinor (1)butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (2)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.
  
  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.Serious - Use Alternative (1)buprenorphine, long-acting injection and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (1)butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .Serious - Use Alternative (1)caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• buspirone

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

• butalbital

  Monitor Closely (1)butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butorphanol

  Monitor Closely (2)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

  Monitor Closely (1)butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• calcium acetate

  Minor (1)caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  Minor (1)caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  Minor (1)caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  Minor (1)caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  Minor (1)caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)butalbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• cannabidiol

  Monitor Closely (1)butalbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.

• capivasertib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.

• captopril

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

• carbachol/brimonidine ophthalmic

  Monitor Closely (1)carbachol/brimonidine ophthalmic and butalbital both increase sedation. Use Caution/Monitor.

• carbamazepine

  Monitor Closely (1)butalbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (2)carbinoxamine and butalbital both increase sedation. Use Caution/Monitor.
  
  carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)cariprazine and butalbital both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)butalbital and carisoprodol both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (2)butalbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• celecoxib

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

• celiprolol

  Monitor Closely (1)butalbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• cenobamate

  Monitor Closely (1)cenobamate, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor.

• cevimeline

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

• chloramphenicol

  Minor (2)chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlordiazepoxide

  Monitor Closely (2)butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (2)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.

• chlorpromazine

  Monitor Closely (2)butalbital and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (1)butalbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cigarette smoking

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

• cilostazol

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

• cimetidine

  Minor (2)cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• cinacalcet

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

• cinnarizine

  Monitor Closely (2)cinnarizine and butalbital both increase sedation. Use Caution/Monitor.
  
  cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ciprofloxacin

  Monitor Closely (1)ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

• clarithromycin

  Minor (2)butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clemastine

  Monitor Closely (2)clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clemastine and butalbital both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)clobazam and butalbital both increase sedation. Use Caution/Monitor.

• clomipramine

  Monitor Closely (4)butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clonazepam

  Monitor Closely (2)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.

• clonidine

  Monitor Closely (1)clonidine and butalbital both increase sedation. Use Caution/Monitor.

• clopidogrel

  Monitor Closely (1)butalbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  Monitor Closely (2)butalbital and clorazepate both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clotrimazole

  Minor (2)clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• clozapine

  Monitor Closely (4)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.
  
  clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• cocaine topical

  Minor (1)butalbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• codeine

  Monitor Closely (2)butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• colchicine

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

• conivaptan

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

• conjugated estrogens

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

• conjugated estrogens, vaginal

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

• copanlisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cortisone

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

• crinecerfont

  Monitor Closely (1)butalbital decreases levels of crinecerfont by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase crinecerfont evening dose 2-fold when coadministered with a moderate CYP3A4 inducer. Do not increase crinecerfont morning dose. .

• cyclobenzaprine

  Monitor Closely (1)butalbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyclosporine

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

• cyproheptadine

  Monitor Closely (2)cyproheptadine and butalbital both increase sedation. Use Caution/Monitor.
  
  cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dalteparin

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

• dantrolene

  Monitor Closely (1)butalbital and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone

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

• daridorexant

  Monitor Closely (1)butalbital and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. Serious - Use Alternative (1)butalbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

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

• darunavir

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

• dasatinib

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

• deferasirox

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

• deflazacort

  Serious - Use Alternative (1)butalbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• desipramine

  Monitor Closely (2)butalbital and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• desloratadine

  Monitor Closely (1)desloratadine and butalbital both increase sedation. Use Caution/Monitor.

• deutetrabenazine

  Monitor Closely (1)butalbital and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

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

• dexbrompheniramine

  Monitor Closely (1)dexbrompheniramine and butalbital both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexchlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)butalbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (2)dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (2)butalbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (2)butalbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.

• dextromoramide

  Monitor Closely (2)butalbital and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  Monitor Closely (2)butalbital and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)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 buccal

  Monitor Closely (3)diazepam buccal and butalbital both increase sedation. Use Caution/Monitor.
  
  diazepam buccal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
  
  butalbital will decrease the level or effect of diazepam buccal 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

  Monitor Closely (3)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.
  
  diazepam intranasal and butalbital both increase sedation. Use Caution/Monitor.

• diazoxide choline

  Monitor Closely (1)diazoxide choline increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Monitor caffeine for adverse effects if coadministered with CYP1A2 inhibitors.

• diclofenac

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

• diethylpropion

  Monitor Closely (2)butalbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and butalbital both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (2)difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)butalbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diltiazem

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

• dimenhydrinate

  Monitor Closely (2)dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dimenhydrinate and butalbital both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)diphenhydramine and butalbital both increase sedation. Use Caution/Monitor.
  
  diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (2)butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  Monitor Closely (2)butalbital and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipyridamole

  Serious - Use Alternative (2)caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
  
  butalbital decreases levels of dipyridamole by increasing metabolism. Contraindicated.

• disopyramide

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

• dobutamine

  Monitor Closely (2)butalbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dobutamine and caffeine both decrease sedation. Use Caution/Monitor.

• docetaxel

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

• donepezil

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

• dopamine

  Monitor Closely (2)butalbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dopamine both decrease sedation. Use Caution/Monitor.

• dopexamine

  Monitor Closely (2)butalbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

• doravirine

  Contraindicated (1)butalbital decreases levels of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine. .

• dosulepin

  Monitor Closely (1)butalbital and dosulepin both increase sedation. Use Caution/Monitor.Minor (1)butalbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxepin

  Monitor Closely (2)butalbital and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxycycline

  Monitor Closely (1)butalbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

• doxylamine

  Monitor Closely (1)butalbital and doxylamine both increase sedation. Use Caution/Monitor.

• dronabinol

  Monitor Closely (1)butalbital will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• droperidol

  Monitor Closely (2)butalbital and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• droxidopa

  Monitor Closely (1)caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• dutasteride

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

• duvelisib

  Serious - Use Alternative (1)butalbital will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• efavirenz

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

• elacestrant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

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

• eletriptan

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

• elinzanetant

  Serious - Use Alternative (1)butalbital decreases levels of elinzanetant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of elinzanetant with moderate or strong CYP3A4 inducers.

• eltrombopag

  Monitor Closely (2)butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• enasidenib

  Monitor Closely (1)enasidenib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Enasidenib (a strong CYP1A2 inhibitor) significantly increases systemic exposure of CYP1A2 substrates. If unable to avoid, dosage reduction of the CYP1A2 substrate may be warranted.

• enoxaparin

  Serious - Use Alternative (1)butalbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

• ensartinib

  Serious - Use Alternative (1)butalbital decreases levels of ensartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ensartinib with strong or moderate CYP3A inducers may decrease ensartinib exposure.

• ephedrine

  Monitor Closely (2)ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (2)epinephrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine inhaled

  Monitor Closely (1)caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (2)butalbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• eplerenone

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

• erdafitinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ergotamine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin base

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  Serious - Use Alternative (1)butalbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• escitalopram

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

• esketamine intranasal

  Monitor Closely (2)esketamine intranasal, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
  
  esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

• esmolol

  Monitor Closely (1)butalbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• estazolam

  Monitor Closely (2)estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and estazolam both increase sedation. Use Caution/Monitor.

• estradiol

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

• estradiol vaginal

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

• estrogens conjugated synthetic

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

• estropipate

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

• eszopiclone

  Monitor Closely (1)eszopiclone and butalbital both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (2)ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and ethanol both increase sedation. Use Caution/Monitor.

• ethinylestradiol

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

• ethosuximide

  Minor (1)ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• etomidate

  Monitor Closely (1)etomidate and butalbital both increase sedation. Use Caution/Monitor.

• etonogestrel

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

• etravirine

  Monitor Closely (3)butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (3)butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  butalbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• everolimus

  Serious - Use Alternative (1)butalbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fedratinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• felodipine

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

• fenfluramine

  Monitor Closely (2)butalbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.

• fentanyl

  Serious - Use Alternative (2)fentanyl, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  Serious - Use Alternative (2)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 intranasal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (1)fentanyl iontophoretic transdermal system and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  Serious - Use Alternative (2)fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  Serious - Use Alternative (2)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.
  
  fentanyl transmucosal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fesoterodine

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

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• fezolinetant

  Contraindicated (1)caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• finasteride

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

• finerenone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)butalbital and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Minor (2)butalbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• fludrocortisone

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

• fluphenazine

  Monitor Closely (2)fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (2)butalbital and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• flurbiprofen

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

• fluvoxamine

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

• fondaparinux

  Serious - Use Alternative (1)butalbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (2)butalbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  formoterol and caffeine both decrease sedation. Use Caution/Monitor.

• fosamprenavir

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

• fosaprepitant

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

• fosphenytoin

  Monitor Closely (1)butalbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fostamatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fostemsavir

  Contraindicated (1)butalbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• frovatriptan

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

• fruquintinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.

• gabapentin

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

• gabapentin enacarbil

  Monitor Closely (2)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.
  
  gabapentin enacarbil and butalbital both increase sedation. Use Caution/Monitor.

• ganaxolone

  Monitor Closely (1)butalbital and ganaxolone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• givosiran

  Serious - Use Alternative (1)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.

• glasdegib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glecaprevir/pibrentasvir

  Monitor Closely (1)butalbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

• gotu kola

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

• grapefruit

  Minor (1)grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• green tea

  Monitor Closely (1)green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.

• griseofulvin

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

• guanfacine

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

• guarana

  Minor (1)guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• guselkumab

  Monitor Closely (1)guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  Monitor Closely (2)haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and haloperidol both increase sedation. Use Caution/Monitor.Minor (1)haloperidol, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

• hawthorn

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

• hemin

  Monitor Closely (1)butalbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• heparin

  Serious - Use Alternative (1)butalbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

• hops

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

• hydrocodone

  Serious - Use Alternative (1)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.

• hydrocortisone

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

• hydromorphone

  Monitor Closely (2)butalbital and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

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

• hydroxyzine

  Monitor Closely (2)hydroxyzine and butalbital both increase sedation. Use Caution/Monitor.
  
  hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ibuprofen

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

• ibuprofen IV

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

• ifosfamide

  Monitor Closely (2)butalbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  butalbital increases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• imatinib

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

• imipramine

  Monitor Closely (5)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.
  
  imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)butalbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• imlunestrant

  Serious - Use Alternative (1)butalbital decreases levels of imlunestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of imlunestrant with strong CYP3A inducers; if unavoidable, increase imlunestrant dose (see Dosage Modifications).

• infigratinib (DSC)

  Serious - Use Alternative (1)butalbital will decrease the level or effect of infigratinib (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• iobenguane I 131

  Serious - Use Alternative (1)caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• isavuconazonium sulfate

  Contraindicated (1)butalbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isocarboxazid

  Contraindicated (1)isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)isocarboxazid, butalbital. Other (see comment). Contraindicated. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.Minor (1)isocarboxazid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• isoproterenol

  Monitor Closely (2)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.

• isradipine

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

• istradefylline

  Serious - Use Alternative (1)butalbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  Minor (1)itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ivosidenib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ixabepilone

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

• kava

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

• ketamine

  Monitor Closely (1)ketamine and butalbital both increase sedation. Use Caution/Monitor.

• ketoconazole

  Minor (3)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ketotifen, ophthalmic

  Monitor Closely (2)butalbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• labetalol

  Monitor Closely (1)butalbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• lamotrigine

  Monitor Closely (1)lamotrigine and butalbital both increase sedation. Use Caution/Monitor.

• lansoprazole

  Minor (1)butalbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• lapatinib

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

• larotrectinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• lazertinib

  Serious - Use Alternative (1)butalbital decreases levels of lazertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lazertinib with strong or moderate CYP3A4 inducers.

• lefamulin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  Serious - Use Alternative (2)butalbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  lemborexant, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

• lenacapavir

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• letermovir

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

• levalbuterol

  Monitor Closely (2)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

  Monitor Closely (1)butalbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levetiracetam

  Monitor Closely (1)levetiracetam and butalbital both increase sedation. Use Caution/Monitor.

• levocetirizine

  Monitor Closely (1)levocetirizine and butalbital both increase sedation. Use Caution/Monitor.

• levoketoconazole

  Minor (3)levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)butalbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• levorphanol

  Monitor Closely (2)levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.Minor (1)butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• lidocaine

  Monitor Closely (1)butalbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• linezolid

  Contraindicated (1)linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)linezolid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• liothyronine

  Minor (1)butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lisdexamfetamine

  Monitor Closely (2)butalbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.

• lofepramine

  Monitor Closely (2)butalbital and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• lofexidine

  Monitor Closely (2)butalbital and lofexidine both increase sedation. Use Caution/Monitor.
  
  lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lonafarnib

  Contraindicated (1)butalbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lopinavir

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

• loprazolam

  Monitor Closely (2)butalbital and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loratadine

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

• lorazepam

  Monitor Closely (2)butalbital and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lorlatinib

  Contraindicated (1)butalbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• lormetazepam

  Monitor Closely (2)butalbital and lormetazepam both increase sedation. Use Caution/Monitor.
  
  lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• losartan

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

• lovastatin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• loxapine

  Monitor Closely (2)butalbital and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumateperone

  Monitor Closely (1)lumateperone and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumefantrine

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

• lurasidone

  Monitor Closely (2)lurasidone, butalbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone and butalbital both increase sedation. Use Caution/Monitor.

• lurbinectedin

  Serious - Use Alternative (1)butalbital decreases levels of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration due to risk of decreased lurbinectedin exposure and reduced efficacy.

• macimorelin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• maraviroc

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

• marijuana

  Monitor Closely (2)butalbital and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mavacamten

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

• meclizine

  Monitor Closely (1)meclizine and butalbital both increase sedation. Use Caution/Monitor.

• melatonin

  Monitor Closely (2)melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

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

• meperidine

  Monitor Closely (2)butalbital and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meprobamate

  Monitor Closely (2)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.

• mestranol

  Monitor Closely (1)butalbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)butalbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

• metaproterenol

  Monitor Closely (2)metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)butalbital and metaxalone both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (3)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.
  
  methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (2)butalbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.

• methazolamide

  Minor (1)methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methocarbamol

  Monitor Closely (1)butalbital and methocarbamol both increase sedation. Use Caution/Monitor.

• methohexital

  Serious - Use Alternative (1)methohexital and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methotrexate

  Monitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.

• methoxyflurane

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

• methsuximide

  Monitor Closely (1)methsuximide and butalbital both increase sedation. Use Caution/Monitor.Minor (1)methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• methylene blue

  Serious - Use Alternative (1)methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• methylenedioxymethamphetamine

  Monitor Closely (2)butalbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.

• methylphenidate

  Monitor Closely (1)caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• methylprednisolone

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

• metoclopramide intranasal

  Serious - Use Alternative (1)butalbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metoprolol

  Monitor Closely (1)butalbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• mexiletine

  Monitor Closely (1)butalbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (1)mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (2)butalbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (3)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.
  
  butalbital and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (2)butalbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and midodrine both decrease sedation. Use Caution/Monitor.

• midostaurin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• migalastat

  Monitor Closely (1)caffeine decreases levels of migalastat by unknown mechanism. Modify Therapy/Monitor Closely. Avoid caffeine ingestion at least 2 hours before and 2 hours after taking migalastat .

• mirtazapine

  Monitor Closely (2)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.

• mitapivat

  Serious - Use Alternative (1)butalbital decreases levels of mitapivat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternant therapies that are not moderate CYP3A inducers during treatment with mitapivat. If unable to avoid coadministration, monitor Hb and titrate beyond 50 mg BID, if necessary, but do not exceed mitapivat dose of 100 mg BID. .

• modafinil

  Monitor Closely (2)butalbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and modafinil both decrease sedation. Use Caution/Monitor.

• molindone

  Monitor Closely (1)molindone and butalbital both increase sedation. Use Caution/Monitor.

• montelukast

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

• morphine

  Monitor Closely (2)butalbital and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  Monitor Closely (2)butalbital and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxonidine

  Monitor Closely (2)butalbital and moxonidine both increase sedation. Use Caution/Monitor.
  
  moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nabilone

  Monitor Closely (2)butalbital and nabilone both increase sedation. Use Caution/Monitor.
  
  nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nadolol

  Monitor Closely (1)butalbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nalbuphine

  Monitor Closely (2)butalbital and nalbuphine both increase sedation. Use Caution/Monitor.
  
  nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• naldemedine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• nateglinide

  Monitor Closely (1)butalbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nebivolol

  Monitor Closely (1)butalbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nelfinavir

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

• nerandomilast

  Serious - Use Alternative (1)butalbital decreases levels of nerandomilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease systemic exposure of nerandomilast, which may reduce its efficacy.

• neratinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• nettle

  Minor (1)nettle increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nicardipine

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

• nifedipine

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

• nilotinib

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

• nimodipine

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

• nirogacestat

  Serious - Use Alternative (1)butalbital will decrease the level or effect of nirogacestat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nisoldipine

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

• nitrendipine

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

• nitrous oxide

  Monitor Closely (1)nitrous oxide and butalbital both increase sedation. Use Caution/Monitor.

• norepinephrine

  Monitor Closely (2)norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norgestrel

  Monitor Closely (1)butalbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

• nortriptyline

  Monitor Closely (2)butalbital and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• olanzapine

  Monitor Closely (3)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.
  
  olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olanzapine/samidorphan

  Monitor Closely (1)butalbital, olanzapine/samidorphan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of diazepam, alcohol, or other CNS acting drugs may potentiate orthostatic hypotension observed with olanzapine. Additive sedation may also occur.

• olopatadine intranasal

  Serious - Use Alternative (1)butalbital and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  Serious - Use Alternative (1)butalbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• omeprazole

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

• opicapone

  Serious - Use Alternative (1)opicapone and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• opium tincture

  Monitor Closely (2)butalbital and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orforglipron

  Serious - Use Alternative (1)butalbital decreases levels of orforglipron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers significantly decrease plasma levels of orforglipron, reducing effectiveness .

• orphenadrine

  Monitor Closely (1)butalbital and orphenadrine both increase sedation. Use Caution/Monitor.

• osilodrostat

  Monitor Closely (1)butalbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

• oxazepam

  Monitor Closely (2)butalbital and oxazepam both increase sedation. Use Caution/Monitor.
  
  oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxybutynin

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

• oxycodone

  Monitor Closely (2)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (2)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.

• ozanimod

  Serious - Use Alternative (1)ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paclitaxel

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

• paclitaxel protein bound

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

• paliperidone

  Monitor Closely (2)butalbital and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• palovarotene

  Serious - Use Alternative (1)butalbital will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• paltusotine

  Monitor Closely (1)butalbital decreases levels of paltusotine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inducers may require an increased paltusotine dose. Do not exceed 3-fold dosage prior to concomitant use or 120 mg daily, whichever is less.

• papaveretum

  Monitor Closely (2)butalbital and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)butalbital and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Monitor Closely (1)butalbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• passion flower

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

• pazopanib

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

• pefloxacin

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

• peginterferon alfa 2a

  Minor (1)peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pemigatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pentazocine

  Monitor Closely (2)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

  Monitor Closely (2)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.Minor (1)pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perphenazine

  Monitor Closely (2)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and perphenazine both increase sedation. Use Caution/Monitor.

• pexidartinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phendimetrazine

  Monitor Closely (2)butalbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.

• phenelzine

  Contraindicated (1)phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• phenindione

  Serious - Use Alternative (1)butalbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.

• phenobarbital

  Monitor Closely (2)butalbital and phenobarbital both increase sedation. Use Caution/Monitor.
  
  phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phentermine

  Monitor Closely (2)butalbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phentermine both decrease sedation. Use Caution/Monitor.

• phenylephrine

  Monitor Closely (2)butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (2)caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
  
  butalbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Monitor Closely (1)butalbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pholcodine

  Monitor Closely (2)pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and pholcodine both increase sedation. Use Caution/Monitor.

• pimavanserin

  Serious - Use Alternative (1)butalbital decreases levels of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pimavanserin with strong or moderate CYP3A4 inducers.

• pimozide

  Monitor Closely (2)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.Minor (1)butalbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pindolol

  Monitor Closely (1)butalbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pioglitazone

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

• pipemidic acid

  Minor (1)pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (2)butalbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• piroxicam

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

• pirtobrutinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

• pitolisant

  Monitor Closely (1)butalbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• polatuzumab vedotin

  Monitor Closely (1)butalbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• posaconazole

  Minor (2)butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• pralsetinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• praziquantel

  Serious - Use Alternative (1)butalbital will decrease the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• prednisolone

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

• prednisone

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

• pregabalin

  Monitor Closely (1)pregabalin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• pretomanid

  Serious - Use Alternative (1)butalbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

• primidone

  Monitor Closely (2)primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital and primidone both increase sedation. Use Caution/Monitor.Minor (1)primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• procarbazine

  Contraindicated (1)procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.

• prochlorperazine

  Monitor Closely (2)butalbital and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promethazine

  Monitor Closely (2)promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine and butalbital both increase sedation. Use Caution/Monitor.

• propafenone

  Monitor Closely (1)butalbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• propofol

  Monitor Closely (1)propofol and butalbital both increase sedation. Use Caution/Monitor.

• propranolol

  Monitor Closely (1)butalbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• propylhexedrine

  Monitor Closely (2)butalbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.

• protamine

  Serious - Use Alternative (1)butalbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (2)butalbital and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• pyrilamine

  Monitor Closely (1)pyrilamine and butalbital both increase sedation. Use Caution/Monitor.

• quazepam

  Monitor Closely (2)butalbital and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  Monitor Closely (3)butalbital and quetiapine both increase sedation. Use Caution/Monitor.
  
  quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

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

• quinine

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

• quizartinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rabeprazole

  Minor (2)butalbital will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  Monitor Closely (2)butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ranolazine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rasagiline

  Monitor Closely (1)rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

• regadenoson

  Serious - Use Alternative (1)caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

• relacorilant

  Serious - Use Alternative (1)butalbital decreases levels of relacorilant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers can decrease concentrations of relacorilant, which may reduce effectiveness.

• remibrutinib

  Serious - Use Alternative (1)butalbital decreases levels of remibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A4 inducers decrease systemic remibrutinib exposure, which may reduce efficacy.

• remifentanil

  Serious - Use Alternative (1)remifentanil and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• remimazolam

  Monitor Closely (1)remimazolam, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

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

• repotrectinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• revumenib

  Serious - Use Alternative (1)butalbital decreases levels of revumenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid revumenib with strong or moderate CYP3A4 inducers.

• rifampin

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

• riluzole

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

• rimegepant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• risperidone

  Monitor Closely (2)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

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

• rose hips

  Minor (1)butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

• sage

  Minor (2)butalbital and sage both increase sedation. Minor/Significance Unknown.
  
  sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)butalbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

• saxagliptin

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

• scopolamine

  Monitor Closely (1)scopolamine and butalbital both increase sedation. Use Caution/Monitor.

• scopolamine intranasal

  Monitor Closely (1)scopolamine intranasal and butalbital both increase sedation. Use Caution/Monitor.

• scullcap

  Monitor Closely (2)butalbital and scullcap both increase sedation. Use Caution/Monitor.
  
  scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• selegiline

  Monitor Closely (1)selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)selegiline transdermal increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• selinexor

  Serious - Use Alternative (1)selinexor, butalbital. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selumetinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of selumetinib with strong or moderate CYP3A4 inducers

• sevabertinib

  Serious - Use Alternative (1)butalbital decreases levels of sevabertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease sevabertinib plasma concentrations, which may reduce efficacy.

• shepherd's purse

  Monitor Closely (2)butalbital and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• sildenafil

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

• silodosin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  Serious - Use Alternative (1)butalbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  Serious - Use Alternative (1)butalbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• smoking

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

• sodium oxybate

  Serious - Use Alternative (2)butalbital, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  sodium oxybate and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• solifenacin

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

• solriamfetol

  Monitor Closely (1)caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)butalbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• sotalol

  Monitor Closely (1)butalbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• stiripentol

  Monitor Closely (1)stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.Serious - Use Alternative (2)butalbital will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.
  
  stiripentol, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sufentanil

  Monitor Closely (2)butalbital and sufentanil both increase sedation. Use Caution/Monitor.
  
  sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sufentanil SL

  Monitor Closely (1)butalbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.Serious - Use Alternative (1)sufentanil SL, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfamethoxazole

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

• sunitinib

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

• suzetrigine

  Serious - Use Alternative (1)butalbital decreases levels of suzetrigine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of suzetrigine with strong or moderate CYP3A inducers.

• tacrolimus

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

• tadalafil

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

• tamoxifen

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

• tapentadol

  Monitor Closely (2)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.

• tasimelteon

  Monitor Closely (1)tasimelteon and butalbital both increase sedation. Use Caution/Monitor.

• temazepam

  Monitor Closely (2)butalbital and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• temsirolimus

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

• terbinafine

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

• terbutaline

  Monitor Closely (2)butalbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  terbutaline and caffeine both decrease sedation. Use Caution/Monitor.

• teriflunomide

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

• tetrabenazine

  Monitor Closely (1)tetrabenazine and butalbital both increase sedation. Use Caution/Monitor.

• tezacaftor

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• thalidomide

  Monitor Closely (1)thalidomide increases effects of butalbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.Serious - Use Alternative (1)thalidomide and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• theophylline

  Monitor Closely (2)butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thiamine

  Minor (1)caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  Monitor Closely (2)butalbital and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (2)butalbital and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thyroid desiccated

  Minor (1)butalbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

• tiagabine

  Monitor Closely (1)tiagabine and butalbital both increase sedation. Use Caution/Monitor.

• tibolone

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

• timolol

  Monitor Closely (1)butalbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• tinidazole

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

• tipranavir

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

• tivozanib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tizanidine

  Monitor Closely (1)tizanidine and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)butalbital will decrease the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• tobacco use

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

• tolcapone

  Serious - Use Alternative (1)tolcapone and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tolterodine

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

• tolvaptan

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• topiramate

  Monitor Closely (2)topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• tramadol

  Monitor Closely (2)butalbital and tramadol both increase sedation. Use Caution/Monitor.
  
  tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Minor (1)tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• trazodone

  Monitor Closely (3)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.Minor (1)butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triamcinolone acetonide injectable suspension

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

• triazolam

  Monitor Closely (3)butalbital and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)butalbital and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)butalbital and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trimipramine

  Monitor Closely (2)butalbital and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triprolidine

  Monitor Closely (2)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.

• tucatinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ubrogepant

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  Serious - Use Alternative (1)butalbital will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

• valbenazine

  Serious - Use Alternative (1)butalbital will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

• valerian

  Serious - Use Alternative (2)valerian increases effects of butalbital by pharmacodynamic synergism. Avoid or Use Alternate Drug. May enhance CNS depression.
  
  valerian and butalbital both increase sedation. Avoid or Use Alternate Drug.

• valproic acid

  Monitor Closely (1)valproic acid and butalbital both increase sedation. Use Caution/Monitor.

• vanzacaftor/tezacaftor/deutivacaftor

  Serious - Use Alternative (1)butalbital decreases levels of vanzacaftor/tezacaftor/deutivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of vanzacaftor/tezacaftor/deutivacaftor with strong or moderate CYP3A inducers.

• vardenafil

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

• verapamil

  Monitor Closely (1)butalbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• vigabatrin

  Monitor Closely (1)vigabatrin and butalbital both increase sedation. Use Caution/Monitor.

• viloxazine

  Monitor Closely (1)viloxazine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Viloxazine (a strong CYP1A2 inhibitor) significantly increases systemic exposure of CYP1A2 substrates. If unable to avoid, dosage reduction of the CYP1A2 substrate may be warranted.

• vinblastine

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

• vincristine

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

• vincristine liposomal

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

• vinorelbine

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

• voclosporin

  Serious - Use Alternative (1)butalbital will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  Serious - Use Alternative (1)butalbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Serious - Use Alternative (1)butalbital decreases levels of voriconazole by increasing metabolism. Contraindicated.Minor (3)butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• warfarin

  Monitor Closely (1)butalbital will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inducers of these isoenzymes and adjust warfarin dose if needed.

• xylometazoline

  Monitor Closely (2)butalbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

• yerba mate

  Minor (1)yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• yohimbine

  Monitor Closely (2)butalbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and yohimbine both decrease sedation. Use Caution/Monitor.

• zaleplon

  Monitor Closely (1)zaleplon and butalbital both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zanubrutinib

  Serious - Use Alternative (1)butalbital will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inducers. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inducer, resume previous dose of zanubrutinib.

• ziconotide

  Monitor Closely (2)butalbital 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.

• ziftomenib

  Serious - Use Alternative (1)butalbital decreases levels of ziftomenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ziftomenib with strong or moderate CYP3A4 inducers, which may decrease ziftomenib systemic exposure, and thereby reduce efficacy.

• zileuton

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

• ziprasidone

  Monitor Closely (2)butalbital and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zoliflodacin

  Contraindicated (1)butalbital decreases levels of zoliflodacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Moderate and strong CYP3A4 inducers are predicted to result in decreased plasma concentrations of zoliflodacin and may reduce its efficacy.

• zolpidem

  Monitor Closely (1)zolpidem and butalbital both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zongertinib

  Serious - Use Alternative (1)butalbital decreases levels of zongertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zongertinib with strong CYP3A inducers. If unavoidable, increase zongertinib dose (see Dosage Modifications in drug monograph).

• zonisamide

  Monitor Closely (1)zonisamide and butalbital both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zotepine

  Monitor Closely (1)butalbital and zotepine both increase sedation. Use Caution/Monitor.

• zuranolone

  Monitor Closely (1)zuranolone and butalbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)butalbital will decrease the level or effect of zuranolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  butalbital, zuranolone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of zuranolone with other CNS depressants may increase impairment of psychomotor performance or CNS depressant effects. If unavoidable, consider dose reduction. .