acetaminophen/dextromethorphan/phenylephrine/guaifenesin (OTC)

Brand and Other Names:Tylenol Cold Multi-Symptom Severe, Tylenol Cold Head Congestion Severe, more...Delsym Cough + Cold Daytime, Sudafed PE Cold & Cough, Mucinex Fast-Max Cold, Flu & Sore Throat, Children's Mucinex Multi-Symptom Cold & Fever, Children's Mucinex Cold, Cough & Sore Throat, Tylenol Cold & Flu Severe
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

acetaminophen/dextromethorphan/phenylephrine/guaifenesin

liquid

  • (650mg/20mg/10mg/400mg)/20mL
  • (325mg/10mg/5mg/200mg)/15mL

tablet

  • 325mg/10mg/5mg/200mg
  • 325mg/15mg/5mg/200mg
  • 325mg/10mg/5mg/100mg

Relief of Cold Symptoms

20 mL [(650mg/20mg/10mg/400mg)/20mL] PO q4hr; not to exceed 120 mL/day

30 mL [(325mg/10mg/5mg/200mg)/15mL] PO q4hr; not to exceed 180 mL/day

2 tablets (325mg/10mg/5mg/200mg) PO q4hr; not to exceed 12 tablets/day

2 tablets (325mg/15mg/5mg/200mg) PO q6-8hr; not to exceed 8 tablets/day

2 tablets (325mg/10mg/5mg/100mg) PO q4hr; not to exceed 12 tablets/day

Dosage Forms & Strengths

acetaminophen/dextromethorphan/phenylephrine/guaifenesin

liquid

  • (325mg/10mg/5mg/200mg)/10mL (Children’s Mucinex Multi-Symptom Cold & Fever; Children's Mucinex Cold, Cough & Sore Throat)
  • (650mg/20mg/10mg/400mg)/20mL

tablet

  • 325mg/10mg/5mg/100mg (Sudafed PE Cold & Cough)
  • 325mg/10mg/5mg/200mg

Relief of Cold Symptoms

< 12 years

  • Not recommended

>12 years

  • 20 mL [(650mg/20mg/10mg/400mg)/20mL] PO q4hr; not to exceed 120 mL/day
  • 30 mL [(325mg/10mg/5mg/200mg)/15mL] PO q4hr; not to exceed 180 mL/day
  • 2 tablets (325mg/10mg/5mg/200mg) PO q4hr; not to exceed 12 tablets/day
  • 2 tablets (325mg/15mg/5mg/200mg) PO q6-8hr; not to exceed 8 tablets/day
  • 2 tablets (325mg/10mg/5mg/100mg) PO q4hr; not to exceed 12 tablets/day
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Interactions

Interaction Checker

and acetaminophen/dextromethorphan/phenylephrine/guaifenesin

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            Contraindicated (7)

            • iobenguane I 123

              phenylephrine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

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

            • linezolid

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

            • phenelzine

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

            • procarbazine

              procarbazine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • selegiline transdermal

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

            • tranylcypromine

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

            Serious - Use Alternative (25)

            • amitriptyline

              amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • amoxapine

              amoxapine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • cabergoline

              cabergoline, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • clomipramine

              clomipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • desflurane

              desflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

              desflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.

            • desipramine

              desipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • dihydroergotamine

              dihydroergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • dihydroergotamine intranasal

              dihydroergotamine intranasal, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • doxapram

              doxapram increases effects of phenylephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

            • doxepin

              doxepin, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • ergoloid mesylates

              ergoloid mesylates, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • ergotamine

              ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • ether

              ether increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • etomidate

              etomidate increases levels of phenylephrine by decreasing metabolism. Contraindicated.

            • imipramine

              imipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • isoflurane

              isoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • lofepramine

              lofepramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • 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.

            • maprotiline

              maprotiline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • methoxyflurane

              methoxyflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • methylergonovine

              methylergonovine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • nortriptyline

              nortriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • 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.

            • propofol

              propofol increases levels of phenylephrine by decreasing metabolism. Contraindicated.

            Monitor Closely (191)

            • albuterol

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

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

            • alfentanil

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

            • alprazolam

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

            • amitriptyline

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

            • amobarbital

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

            • amoxapine

              amoxapine increases and phenylephrine 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 phenylephrine both decrease sedation. Use Caution/Monitor.

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

            • aripiprazole

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

            • armodafinil

              armodafinil and phenylephrine 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.

            • atomoxetine

              atomoxetine, phenylephrine. Other (see comment). Use Caution/Monitor. Comment: Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine.

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

            • belladonna and opium

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

            • benperidol

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

            • benzphetamine

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

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

            • bromocriptine

              bromocriptine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

            • brompheniramine

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • carbinoxamine

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpheniramine

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

            • chlorpromazine

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

              chlorpromazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • cinnarizine

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

            • clemastine

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

            • clomipramine

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

            • codeine

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

            • cyclizine

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

            • cyproheptadine

              cyproheptadine increases and phenylephrine 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 .

            • desipramine

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

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

            • dextroamphetamine

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

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

            • dextromoramide

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

            • diamorphine

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

            • diethylpropion

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

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

            • difenoxin hcl

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

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

            • dopamine

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

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

            • dopexamine

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

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

            • doxepin

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

            • droperidol

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

            • droxidopa

              phenylephrine 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 phenylephrine both decrease sedation. Use Caution/Monitor.

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

              ephedrine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • epinephrine

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

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

            • epinephrine inhaled

              phenylephrine, 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 phenylephrine both decrease sedation. Use Caution/Monitor.

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

            • estazolam

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

            • ethanol

              ethanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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

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

              fenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              fluphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • flurazepam

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

            • formoterol

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

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

            • haloperidol

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

            • hydralazine

              hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • hydromorphone

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

            • hydroxyzine

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

            • iloperidone

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

            • indacaterol, inhaled

              phenylephrine increases effects of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

            • insulin degludec

              phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

            • insulin degludec/insulin aspart

              phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

            • insulin inhaled

              phenylephrine decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

            • 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 phenylephrine both decrease sedation. Use Caution/Monitor.

              isoproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine 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.

            • levalbuterol

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

              levalbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lisdexamfetamine

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

              lisdexamfetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofexidine

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

            • lorazepam

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

            • lormetazepam

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

            • loxapine

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

            • loxapine inhaled

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

            • maprotiline

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

            • marijuana

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

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

            • methadone

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

            • methamphetamine

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

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

            • methyldopa

              methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

            • methylenedioxymethamphetamine

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

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

            • midazolam

              midazolam increases and phenylephrine 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

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

              midodrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • modafinil

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

            • morphine

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

            • motherwort

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

            • moxonidine

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

            • nabilone

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

            • nadolol

              nadolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

            • nalbuphine

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

            • norepinephrine

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

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

            • nortriptyline

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

            • olanzapine

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

            • olodaterol inhaled

              phenylephrine and olodaterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Caution with coadministration of adrenergic drugs by any route because of additive sympathetic effects

            • opium tincture

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

            • oxazepam

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

            • oxycodone

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

            • oxymetazoline topical

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

            • oxymorphone

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

            • oxytocin

              oxytocin increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor.

            • paliperidone

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

            • papaveretum

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

            • pentazocine

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

            • pentobarbital

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

            • perphenazine

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

              perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phendimetrazine

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

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

            • phenobarbital

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

            • phentermine

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

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

            • pholcodine

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

            • pimozide

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

            • pindolol

              pindolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

            • pirbuterol

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

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

            • primidone

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

            • prochlorperazine

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

              prochlorperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • promazine

              promazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • promethazine

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

              promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • propofol

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

            • propranolol

              propranolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

            • propylhexedrine

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

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

            • protriptyline

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

            • pseudoephedrine

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

            • quazepam

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

            • quetiapine

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

            • rasagiline

              rasagiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

            • risperidone

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

            • safinamide

              phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • salmeterol

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

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

            • scullcap

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

            • secobarbital

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

            • selegiline

              selegiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

            • shepherd's purse

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

            • solriamfetol

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

            • sufentanil

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

            • tapentadol

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

            • terbutaline

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

              terbutaline and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              thioridazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • thiothixene

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

            • timolol

              timolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

            • tinidazole

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

            • topiramate

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

            • tramadol

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

            • trazodone

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

            • triazolam

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

            • triclofos

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

            • trifluoperazine

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

              trifluoperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • trimipramine

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

            • triprolidine

              triprolidine increases and phenylephrine 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

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

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

            Minor (59)

            • acetazolamide

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

            • albiglutide

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

            • alfuzosin

              alfuzosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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.

            • asenapine

              asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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.

            • carbamazepine

              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.

            • clonazepam

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

            • 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.

            • desmopressin

              desmopressin increases effects of phenylephrine by pharmacodynamic synergism. 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.

            • doxazosin

              doxazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • enoxaparin

              acetaminophen increases effects of enoxaparin by unknown mechanism. 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 phenylephrine 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.

            • 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.

            • green tea

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

            • heparin

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

            • isoniazid

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

            • lacosamide

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

            • 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.

            • moxisylyte

              moxisylyte, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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.

            • 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.

            • phenoxybenzamine

              phenoxybenzamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • phentolamine

              phentolamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • phenytoin

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

            • prazosin

              prazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • primidone

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

            • protamine

              acetaminophen increases effects of protamine by unknown mechanism. 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 phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • silodosin

              silodosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • terazosin

              terazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

            • tiagabine

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

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            Adverse Effects

            Frequency Not Defined

            Hypertension

            Reflex tachycardia

            Severe peripheral and visceral vasoconstriction

            Dizziness

            Drowsiness

            Excitability

            Headache

            Restlessness

            Tremor

            Dermatologic rash

            Nausea

            Vomiting

            Anemia blood dyscrasias (neutropenia, pancytopenia, leukopenia)

            Bilirubin and alkaline phosphatase may increase

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            Warnings

            Contraindications

            Documented hypersensitivity to any of the drugs or components

            Cautions

            Cautions

            Severe or recurrent pain or high or continued fever may indicate a serious illness

            Acetaminophen

            • Hypersensitivity and anaphylactic reactions reported; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur
            • Use caution in patients with hepatic impairment or active liver disease; acetaminophen hepatotoxicity possible in chronic alcoholics following various dose levels
            • Risk of hepatotoxicity is higher in patients taking chronic high dose, or use of more than one acetaminophen-containing product
            • Acetaminophen contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose
            • 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
            • Use caution in patients with severe renal impairment; consider dosage adjustments
            • Severe or recurrent pain or high or continued fever may indicate a serious illness
            • Use with caution in patients with G6PD deficiency
            • Use caution in patients with chronic malnutrition
            • Limit acetaminophen dose from all sources and routes to <4 g/day in adults

            Dextromethorphan

            • Do not take for persistent or chronic cough associated with smoking, asthma, or emphysema, or if it is accompanied by excessive phlegm unless directed by a healthcare provider; may slow respiration rate
            • Hallucinations, confusion, agitation, hyper-reflexia, shivering, myoclonus, and tachycardia may occur
            • Caution in children younger than 6 years
            • Use caution in patients who are sedated, debilitated or confined to supine position

            Phenylephrine

            • Avoid or use with extreme caution in patients with heart failure or cardiogenic shock; cardiac output may decrease with increased systemic vascular resistance
            • Avoid use in patients with hypertension; monitor blood pressure closely and adjust infusion rate; use is contraindicated in severe hypertension
            • May cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, especially in patients with peripheral vascular disease
            • Patients with spinal cord injury or other autonomic dysfunction may experience exaggerated increase in blood pressure response to therapy
            • May increase the need for renal replacement therapy in patients with septic shock; monitor renal function

            Guaifenesin

            • Guaifenesin is not for administration in persistent cough associated with chronic bronchitis, smoking, asthma, or accompanied with excessive secretions
            • If cough is accompanied by excessive phlegm, consult healthcare provider prior to use
            • Consult healthcare provider if symptoms are accompanied by fever, rash, or persistent headache
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            Pregnancy & Lactation

            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

            Dextromethorphan: Cough suppressant that acts centrally on the cough center in the medulla

            Guaifenesin: Increases respiratory tract fluid secretions and helps to loosen phlegm and bronchial secretions

            Phenylephrine: Vasoconstrictor and a decongestant that relieves symptoms resulting from irritation of upper respiratory tract tissue; shrinks swollen mucous membranes, reduces nasal congestion and tissue hyperemia

            Acetaminophen: Blocks pain impulse generation peripherally and may inhibit the generation of prostaglandin in the CNS; reduces fever by inhibiting the hypothalamic heat-regulating center

            Pharmacokinetics

            Acetaminophen

            • Peak plasma time: 10-60 min (PO immediate release); 60-120 min (PO extended release); 6 hr (PO 500 mg tablet); 8 hr (PO 650 mg extended release tablet)
            • Vd: 1 L/kg
            • Protein binding: 10-25%
            • Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic acid)
            • Half-life: 1.25-3hr
            • Excretion: Urine

            Dextromethorphan

            • Onset: 15-30 min
            • Duration: 3-6 hr
            • Metabolism: Hepatic P450 enzyme CYP2D6
            • Excretion: Urine
            • Half-life: 2-4 hr (extensive metabolizers); 24 hr (poor metabolizers)
            • Peak plasma time: 2-3 hr

            Phenylephrine

            • Half-life: 2-3 hr
            • Onset: 10-15 min
            • Duration: 15 min
            • Bioavailability: < 38%
            • Excretion: Urine (80-90%)
            • Peak plasma time: 0.75-2 hr
            • Vd: 26-61 L
            • Vdss: 340 L

            Guaifenesin

            • Half-Life: 1 hr
            • Onset: 30 min
            • Duration: 4-6 hr
            • Metabolism: Liver
            • Metabolite: b-(2-methoxyphenoxy) lactic acid
            • Excretion: Urine
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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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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.