acetaminophen/caffeine/isometheptene (Rx)

Brand and Other Names:Prodrin
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

acetaminophen/caffeine/isometheptene

tablet

  • 325mg/20mg/65mg

Migraine Headache

1 or 2 tablets PO at onset of headache, then 1 tablet hourly until relieved; not to exceed 5 tablets/12 hr

Tension Headache

1-2 tablets PO q4hr; not to exceed 8 tablets/24 hr

Safety and efficacy not established

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Interactions

Interaction Checker

and acetaminophen/caffeine/isometheptene

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            Contraindicated (7)

            • isocarboxazid

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

              isocarboxazid, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

            • linezolid

              linezolid, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

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

            • phenelzine

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

              phenelzine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

            • 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, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

            • 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.

              tranylcypromine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

            Serious - Use Alternative (10)

            • abametapir

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

            • 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.

            • dipyridamole

              caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.

            • 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.

            • 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.

            • lonafarnib

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

            • 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.

            • pexidartinib

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

            • pretomanid

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

            • regadenoson

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

            Monitor Closely (189)

            • albuterol

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

            • alfentanil

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

            • alprazolam

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

            • amitriptyline

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

            • amobarbital

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

            • amoxapine

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

            • apalutamide

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

            • arformoterol

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

            • aripiprazole

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

            • armodafinil

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

            • atogepant

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

            • avapritinib

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

            • axitinib

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

            • azelastine

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

            • belladonna and opium

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

            • benperidol

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

            • benzphetamine

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

            • brompheniramine

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

            • bupivacaine implant

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

            • buprenorphine buccal

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

            • busulfan

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

            • butabarbital

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

            • butalbital

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

            • butorphanol

              butorphanol 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.

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpheniramine

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

            • chlorpromazine

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

            • cinnarizine

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

            • clomipramine

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

            • codeine

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

            • cyclizine

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

            • cyproheptadine

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

            • dapsone topical

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

            • deferasirox

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

            • desipramine

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromoramide

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

            • diamorphine

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

            • diethylpropion

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

            • difenoxin hcl

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • dopamine

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

            • dopexamine

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

            • doxepin

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

            • droperidol

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

            • droxidopa

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

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

            • eltrombopag

              eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • ephedrine

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

            • epinephrine

              epinephrine and caffeine both decrease sedation. 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

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

            • esketamine intranasal

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

            • estazolam

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

            • ethanol

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

            • ethinylestradiol

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

            • exenatide injectable solution

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

            • exenatide injectable suspension

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

            • fenfluramine

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

            • fexinidazole

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

            • finerenone

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

            • flibanserin

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

            • fluphenazine

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

            • flurazepam

              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

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

            • green tea

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

            • guselkumab

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

            • haloperidol

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

            • hydromorphone

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

            • hydroxyzine

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

            • iloperidone

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

            • imatinib

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

            • imipramine

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

            • isavuconazonium sulfate

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

            • isoniazid

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

            • isoproterenol

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

            • ivacaftor

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

            • ketotifen, ophthalmic

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

            • lemborexant

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

            • letermovir

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

            • levalbuterol

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

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.

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

            • levorphanol

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

            • levothyroxine

              caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

            • lisdexamfetamine

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

            • lixisenatide

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

            • lofepramine

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

            • lofexidine

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

            • lomitapide

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

            • loprazolam

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

            • lorazepam

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

            • lormetazepam

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

            • loxapine

              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.

            • maprotiline

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

            • marijuana

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

            • melatonin

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

            • meperidine

              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.

            • metaproterenol

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

            • methadone

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

            • methamphetamine

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

            • methotrexate

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

            • methylenedioxymethamphetamine

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

            • methylphenidate

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

            • midazolam

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

            • midazolam intranasal

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

            • midodrine

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

            • mipomersen

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

            • mirtazapine

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

            • modafinil

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

            • morphine

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

            • motherwort

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

            • moxonidine

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

            • nabilone

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

            • nalbuphine

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

            • norepinephrine

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

            • nortriptyline

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

            • olanzapine

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

            • opium tincture

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

            • oxazepam

              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.

            • oxymorphone

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

            • paliperidone

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

            • papaveretum

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

            • pefloxacin

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

            • pentazocine

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

            • pentobarbital

              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.

            • phendimetrazine

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

            • phenobarbital

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

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

            • pholcodine

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

            • pimozide

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

            • pirbuterol

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

            • primidone

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

            • prochlorperazine

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

            • promethazine

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

            • propylhexedrine

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

            • protriptyline

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

            • quazepam

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

            • quetiapine

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

            • rasagiline

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

            • risperidone

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

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

            • scullcap

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

            • secobarbital

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

            • solriamfetol

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

            • 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.

            • tapentadol

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

            • tazemetostat

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

            • temazepam

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

            • terbutaline

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

            • teriflunomide

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

            • tetracaine

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

            • thioridazine

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

            • thiothixene

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

            • tinidazole

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

            • topiramate

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

            • tramadol

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

            • trazodone

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

            • triazolam

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

            • triclofos

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

            • trifluoperazine

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

            • trimipramine

              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.

            • warfarin

              acetaminophen increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • xylometazoline

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

            Minor (92)

            • acetazolamide

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

            • adenosine

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

            • albiglutide

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

            • 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.

            • amobarbital

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

            • antithrombin alfa

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

            • antithrombin III

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

            • argatroban

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

            • armodafinil

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

            • bemiparin

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

            • bivalirudin

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

            • butabarbital

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

            • butalbital

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

            • calcium acetate

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

            • calcium carbonate

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

            • calcium chloride

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

            • calcium citrate

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

            • calcium gluconate

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

            • carbamazepine

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

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

            • cholestyramine

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

            • clonazepam

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

            • clotrimazole

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

            • colestipol

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

            • dalteparin

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

            • diazepam

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

            • disulfiram

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

            • enoxaparin

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • ethanol

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

              ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

            • ethosuximide

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

            • eucalyptus

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

            • felbamate

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

            • fluconazole

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

            • fondaparinux

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

            • fosphenytoin

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

            • gabapentin

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

            • gabapentin enacarbil

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

            • grapefruit

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

            • green tea

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

            • guarana

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

            • heparin

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

            • isoniazid

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

              isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

            • itraconazole

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

            • lacosamide

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

            • ketoconazole

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

            • lamotrigine

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

            • levetiracetam

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

            • liraglutide

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

            • lorazepam

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

            • methsuximide

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

            • metoclopramide

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

            • metronidazole

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

            • mexiletine

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

            • miconazole vaginal

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

            • modafinil

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

            • oxcarbazepine

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

            • oxybutynin

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

            • oxybutynin topical

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

            • oxybutynin transdermal

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

            • peginterferon alfa 2a

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

            • pentobarbital

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

            • phenindione

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

            • phenobarbital

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

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

            • phenytoin

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

            • pipemidic acid

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

            • posaconazole

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

            • primidone

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

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

            • protamine

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

            • rifampin

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

            • rifabutin

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

            • rifampin

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

            • rufinamide

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

            • ruxolitinib

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

            • sage

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

            • secobarbital

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

            • smoking

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

            • tiagabine

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

            • tobacco use

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

            • topiramate

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

            • valproic acid

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

            • verapamil

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

            • voriconazole

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

            • yerba mate

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

            • zileuton

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

            • zonisamide

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

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            Adverse Effects

            Frequency Not Defined

            Rash

            Transient dizziness

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            Warnings

            Black Box Warnings

            Medication errors and hepatotoxicity with acetaminophen

            • Take care when prescribing, preparing, and administering acetaminophen to avoid dosing errors which could result in accidental overdose and death
            • In particular, be careful to ensure that
              • The dose in milligrams (mg) and milliliters (mL) is not confused
              • The dosing is based on weight for patients <50 kg
              • Infusion pumps are properly programmed
              • The total daily dose of acetaminophen from all sources does not exceed maximum daily limits
            • Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death
            • Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than one acetaminophen-containing product

            Contraindications

            Glaucoma

            Severe renal disease

            Severe hypertension

            Organic heart disease

            Severe hepatic disease

            Coadministration or within 2 weeks of MAOIs

            Cautions

            Cautions with history of hypertension, peripheral vascular disease, and after recent cardiovascular events

            Acetaminophen

            • Reports of acute liver failure, at times resulting in liver transplant and death; most of the cases of liver injury are associated with doses exceeding 4 g/day, and often involve >1 acetaminophen-containing product (see Black Box Warnings)
            • Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash
            • Postmarketing reports of hypersensitivity and anaphylaxis
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            Pregnancy & Lactation

            Pregnancy Category: C Lactation: Unknown if distributed in human breast milk

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Acetaminophen: Nonnarcotic analgesic; reduces the perception of pain impulses originating from dilated cerebral vessels

            Caffeine: Cranial vasoconstrictor; enhances vasoconstrictor effect of isometheptene; also used as a central stimulant for relief of headache

            Isometheptene: Sympathomimetic amine that acts by constricting dilated cranial and cerebral arterioles, thus reducing the stimuli that lead to vascular headaches

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            Patient Handout

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.