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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases

      acetaminophen/caffeine/pyrilamine (OTC)

      Brand and Other Names:Midol Complete
      • Print

      Dosing & Uses

      AdultPediatric

      Dosing Forms & Strengths

      acetaminophen/caffeine/pyrilamine

      caplet

      • 500mg/60mg/15mg

      Menstrual Symptoms

      Indicated for temporary relief of symptoms associated with menstrual periods

      2 caplets PO q6hr prn; not to exceed 6 caplets/day

      Dosage Forms & Strengths

      acetaminophen/caffeine/pyrilamine

      caplet

      • 500mg/60mg/15mg

      Menstrual Symptoms

      Indicated for temporary relief of symptoms associated with menstrual periods

      <12 years: Safety and efficacy not established

      12 years or older: 2 caplets PO q6hr prn; not to exceed 8 caplets/day

      Next:

      Interactions

      Interaction Checker

      and acetaminophen/caffeine/pyrilamine

      No Results

         activity indicator 
        No Interactions Found
        Interactions Found

        Contraindicated

          Serious - Use Alternative

            Significant - Monitor Closely

              Minor

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                 activity indicator 

                Contraindicated (7)

                • fezolinetant

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

                • isocarboxazid

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

                • linezolid

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

                • 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.

                Serious - Use Alternative (9)

                • 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 (93)

                • acrivastine

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

                • 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.

                • amisulpride

                  amisulpride and pyrilamine both increase sedation. 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.

                • asenapine

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

                • asenapine transdermal

                  asenapine transdermal and pyrilamine both increase 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

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

                  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.

                • benzhydrocodone/acetaminophen

                  benzhydrocodone/acetaminophen and pyrilamine both increase sedation. 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.

                • brexpiprazole

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

                • brimonidine

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

                • brivaracetam

                  brivaracetam and pyrilamine both increase 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.

                • buprenorphine subdermal implant

                  buprenorphine subdermal implant and pyrilamine both increase sedation. Use Caution/Monitor.

                • buprenorphine transdermal

                  buprenorphine transdermal and pyrilamine both increase sedation. Use Caution/Monitor.

                • buprenorphine, long-acting injection

                  buprenorphine, long-acting injection and pyrilamine both increase sedation. 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

                  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.

                • ganaxolone

                  pyrilamine and ganaxolone both increase 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.

                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.

                • 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.

                • levoketoconazole

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

                • 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.

                • ruxolitinib topical

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

                • sage

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

                • 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 (acetaminophen)

                Pruritic maculopapular rash

                Urticaria

                Laryngeal edema

                Angioedema

                Anaphylactoid reaction

                Thrombocytopenia

                Leukopenia

                Pancytopenia

                Neutropenia

                Thrombocytopenic purpura

                Agranulocytosis

                Hepatotoxicity

                Frequency Not Defined (caffeine)

                Insomnia

                Restlessness

                Nervousness

                Tremor

                Tinnitus

                Irritability

                Nausea

                Vomiting

                Diarrhea

                Tachycardia

                Diuresis

                Palpitations (dose dependent)

                Frequency Not Defined (pyrilamine)

                Sedation

                Xerostomia

                Blurred vision

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                Warnings

                Contraindications

                Hypersensitivity to drug or components

                Cautions

                Risk of hepatotoxicity; risk is higher in alcoholics or with use of more than one acetaminophen-containing product

                Caution regarding daily acetaminophen consumption; do not exceed 3-4 g/day and do not take for prolonged duration G6PD deficiency

                May cause CNS depression, which may impair mental and physical abilities; caution patients about performing tasks requiring mental alertness, including operating heavy machinery

                Caution with glaucoma, difficulty in urination caused by prostate gland enlargement, and emphysema or chronic bronchitis

                Allergic reactions reported with acetaminophen; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur

                Additive sedation may occur if used with alcohol or sedative drugs

                Acetaminophen associated with increased 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

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                Pregnancy & Lactation

                Pregnancy category: C

                Lactation: Excreted in breast milk

                Pregnant or breastfeeding patients should seek advice of health professional before using OTC drugs

                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: Acts on hypothalamus to produce analgesia

                Caffeine: Vasoconstrictive properties may be helpful when treating vascular headaches

                Pyrilamine: Elicits mild diuretic properties

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                Images

                No images available for this drug.
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                Patient Handout

                A Patient Handout is not currently available for this monograph.
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