acetaminophen/doxylamine/dextromethorphan/pseudoephedrine (OTC)

Brand and Other Names:Vicks NyQuil D, Vicks NyQuil
Sections

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

acetaminophen/doxylamine/dextromethorphan/pseudoephedrine

liquid

  • (325mg/6.25mg/15mg/30mg)/15mL

Nasal Congestion, Rhinorrhea, Sore Throat, Cough, Fever, Headache

30 mL PO q6-8hr; not to exceed 4 doses/day

Dosage Forms & Strengths

acetaminophen/doxylamine/dextromethorphan/pseudoephedrine

liquid

  • (325mg/6.25mg/15mg/30mg)/15mL

Nasal Congestion, Rhinorrhea, Sore Throat, Cough, Fever, Headache

Vicks NyQuil D

  • <12 years old: Ask a pediatrician
  • >12 years old: 30 mL PO q6-8hr; not to exceed 4 doses/day
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Interactions

Interaction Checker

and acetaminophen/doxylamine/dextromethorphan/pseudoephedrine

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            Contraindicated (15)

            • dihydroergotamine

              dihydroergotamine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • dihydroergotamine inhaled

              dihydroergotamine inhaled increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • dihydroergotamine intranasal

              dihydroergotamine intranasal increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • ergoloid mesylates

              ergoloid mesylates increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • ergonovine

              ergonovine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • ergotamine

              ergotamine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • isocarboxazid

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

            • linezolid

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

            • methylergonovine

              methylergonovine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

            • phenelzine

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

            • procarbazine

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

            • rasagiline

              rasagiline increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • selegiline

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

            • selegiline transdermal

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

            • tranylcypromine

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

            Serious - Use Alternative (37)

            • amitriptyline

              amitriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. 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 increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • benzhydrocodone/acetaminophen

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

            • cabergoline

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

            • calcium/magnesium/potassium/sodium oxybates

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

            • clomipramine

              clomipramine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • cocaine topical

              cocaine topical increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • desipramine

              desipramine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • desvenlafaxine

              desvenlafaxine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • doxapram

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

            • doxepin

              doxepin increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • duloxetine

              duloxetine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • fentanyl

              fentanyl, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl intranasal

              fentanyl intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transdermal

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

            • fentanyl transmucosal

              fentanyl transmucosal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • hydrocodone

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

            • imipramine

              imipramine increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • iobenguane I 123

              pseudoephedrine decreases effects of iobenguane I 123 by receptor binding competition. Avoid or Use Alternate Drug. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results. Do not administer pseudoephedrine until at least 7 days after each iobenguane dose.

            • iobenguane I 131

              pseudoephedrine decreases effects of iobenguane I 131 by receptor binding competition. Avoid or Use Alternate Drug. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results. Do not administer pseudoephedrine until at least 7 days after each iobenguane dose.

            • isocarboxazid

              isocarboxazid increases effects of doxylamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

            • isoflurane

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

            • lemborexant

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

            • levomilnacipran

              levomilnacipran increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • lofepramine

              lofepramine, pseudoephedrine. 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, pseudoephedrine. 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 pseudoephedrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • methylene blue

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

            • metoclopramide intranasal

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

            • milnacipran

              milnacipran increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • olopatadine intranasal

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

            • ozanimod

              ozanimod increases toxicity of pseudoephedrine 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.

            • protriptyline

              protriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            Monitor Closely (264)

            • acetazolamide

              acetazolamide will increase the level or effect of pseudoephedrine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • acrivastine

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

            • albuterol

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

            • alfentanil

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

            • alfuzosin

              pseudoephedrine decreases effects of alfuzosin by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • alprazolam

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

            • aluminum hydroxide

              aluminum hydroxide will increase the level or effect of pseudoephedrine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor. Caution advised with frequent or high dose antacids

            • amifampridine

              doxylamine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amisulpride

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

            • amitriptyline

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

            • ammonium chloride

              ammonium chloride decreases effects of pseudoephedrine by unknown mechanism. Use Caution/Monitor. Urinary excretion of indirect acting alpha/beta agonists (eg, pseudoephedrine) may increase when administered concomitantly with urinary acidifying agents, resulting in lower serum concentrations.

            • amobarbital

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

            • amoxapine

              doxylamine and amoxapine both increase sedation. 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.

            • apomorphine

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

            • arformoterol

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

            • aripiprazole

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

            • asenapine

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

            • asenapine transdermal

              asenapine transdermal and doxylamine 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

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

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

            • axitinib

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

            • azelastine

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

            • baclofen

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

            • belladonna and opium

              doxylamine and belladonna and opium both increase sedation. Use Caution/Monitor.

            • benperidol

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

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen and doxylamine both increase sedation. Use Caution/Monitor.

            • benzphetamine

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

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

            • brexanolone

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

            • bromocriptine

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

            • brexpiprazole

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

            • brimonidine

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

            • brivaracetam

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

            • brompheniramine

              brompheniramine and doxylamine both increase sedation. 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

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

            • buprenorphine buccal

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

            • buprenorphine subdermal implant

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

            • buprenorphine transdermal

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

            • buprenorphine, long-acting injection

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

              buprenorphine, long-acting injection and doxylamine 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 and doxylamine both increase sedation. Use Caution/Monitor.

            • butalbital

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

            • butorphanol

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

            • carbinoxamine

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

            • carisoprodol

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

            • cenobamate

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpheniramine

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

            • chlorpromazine

              chlorpromazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

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

            • chlorzoxazone

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

            • dapsone topical

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

            • dexfenfluramine

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

            • cinnarizine

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

            • clemastine

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

            • clobazam

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

            • clomipramine

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

            • clonazepam

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

            • clonidine

              clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

            • clorazepate

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

            • clozapine

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

            • codeine

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

            • cyclizine

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

            • cyclobenzaprine

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

            • cyproheptadine

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

            • dantrolene

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

            • daridorexant

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

            • desipramine

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

            • deutetrabenazine

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromoramide

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

            • diamorphine

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

            • diazepam

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

            • diazepam intranasal

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

            • diethylpropion

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

            • difelikefalin

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

            • difenoxin hcl

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • dopamine

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

            • dopexamine

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

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

            • dosulepin

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

            • doxazosin

              pseudoephedrine decreases effects of doxazosin by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • doxepin

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

            • droperidol

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

            • droxidopa

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

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

            • epinephrine

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

            • epinephrine inhaled

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

            • esketamine intranasal

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

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

            • ethanol

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

            • etomidate

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

            • fenfluramine

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

            • fentanyl

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

            • fentanyl intranasal

              fentanyl intranasal and doxylamine both increase sedation. Use Caution/Monitor.

            • fentanyl iontophoretic transdermal system

              fentanyl iontophoretic transdermal system and doxylamine both increase sedation. Use Caution/Monitor.

            • fentanyl transdermal

              fentanyl transdermal and doxylamine both increase sedation. 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

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

              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

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

              fluphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

            • 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.

            • flurazepam

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

            • formoterol

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

            • gabapentin

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

            • gabapentin enacarbil

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

            • ganaxolone

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

            • gotu kola

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

            • haloperidol

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

            • hawthorn

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

            • hops

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

            • hyaluronidase

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

            • hydralazine

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

            • hydromorphone

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

            • hydroxyzine

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

            • iloperidone

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

            • imipramine

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

            • insulin degludec

              pseudoephedrine 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

              pseudoephedrine 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 detemir

              pseudoephedrine decreases effects of insulin detemir 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 glargine

              pseudoephedrine decreases effects of insulin glargine 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

              pseudoephedrine 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.

            • insulin regular human

              pseudoephedrine decreases effects of insulin regular human 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 pseudoephedrine 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 .

            • kava

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

            • ketamine

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

            • ketotifen, ophthalmic

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

            • lasmiditan

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

            • 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 pseudoephedrine 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

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

            • lisdexamfetamine

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

            • lixisenatide (DSC)

              lixisenatide (DSC) 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

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

            • lofexidine

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

            • lorazepam

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

            • lormetazepam

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

            • loxapine

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

            • loxapine inhaled

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

            • lurasidone

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

            • maprotiline

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

            • marijuana

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

            • metaxalone

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

            • methadone

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

            • methamphetamine

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

            • methenamine

              methenamine decreases effects of pseudoephedrine by unknown mechanism. Use Caution/Monitor. Urinary excretion of indirect acting alpha/beta agonists (eg, pseudoephedrine) may increase when administered concomitantly with urinary acidifying agents, resulting in lower serum concentrations.

            • methocarbamol

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

            • methyldopa

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

            • methylenedioxymethamphetamine

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

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

            • midazolam

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

            • midazolam intranasal

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

            • 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

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

            • morphine

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

            • motherwort

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

            • moxonidine

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

            • nabilone

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

            • nalbuphine

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

            • nateglinide

              pseudoephedrine decreases effects of nateglinide by pharmacodynamic antagonism. Use Caution/Monitor. Coadministration may reduce nateglinide's hypoglycemic action.

            • norepinephrine

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

            • nortriptyline

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

            • olanzapine

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

            • oliceridine

              oliceridine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • olodaterol inhaled

              pseudoephedrine 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

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

            • orphenadrine

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

            • oxazepam

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

            • oxycodone

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

            • oxymorphone

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

            • oxytocin

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

            • paliperidone

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

            • papaveretum

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

            • papaverine

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

            • passion flower

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

            • pentazocine

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

            • pentobarbital

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

            • perphenazine

              perphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

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

            • phendimetrazine

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

            • phenelzine

              phenelzine increases effects of doxylamine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

            • phenobarbital

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

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

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

            • pholcodine

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

            • pirbuterol

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

            • pimozide

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

            • potassium phosphate

              potassium phosphate decreases effects of pseudoephedrine by unknown mechanism. Use Caution/Monitor. Urinary excretion of indirect acting alpha/beta agonists (eg, pseudoephedrine) may increase when administered concomitantly with urinary acidifying agents, resulting in lower serum concentrations.

            • pregabalin

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

            • primidone

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

            • prochlorperazine

              prochlorperazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

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

            • promazine

              promazine, pseudoephedrine. 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 and doxylamine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine, pseudoephedrine. 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 and doxylamine both increase sedation. Use Caution/Monitor.

            • propylhexedrine

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

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

            • protriptyline

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

            • safinamide

              pseudoephedrine 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.

            • quazepam

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

            • quetiapine

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

            • ramelteon

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

            • remimazolam

              remimazolam, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • risperidone

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

            • salmeterol

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

            • scullcap

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

            • secobarbital

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

            • serdexmethylphenidate/dexmethylphenidate

              serdexmethylphenidate/dexmethylphenidate and pseudoephedrine both decrease sedation. Use Caution/Monitor.

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

            • sevoflurane

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

            • shepherd's purse

              doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • silodosin

              pseudoephedrine decreases effects of silodosin by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • sodium bicarbonate

              sodium bicarbonate will increase the level or effect of pseudoephedrine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor. Caution advised with frequent or high dose antacids

            • sodium citrate/citric acid

              sodium citrate/citric acid will increase the level or effect of pseudoephedrine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • sodium lactate

              sodium lactate will increase the level or effect of pseudoephedrine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • sodium phosphates, IV

              sodium phosphates, IV decreases effects of pseudoephedrine by unknown mechanism. Use Caution/Monitor. Urinary excretion of indirect acting alpha/beta agonists (eg, pseudoephedrine) may increase when administered concomitantly with urinary acidifying agents, resulting in lower serum concentrations.

            • solriamfetol

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

            • spironolactone

              spironolactone decreases effects of pseudoephedrine by pharmacodynamic antagonism. Use Caution/Monitor.

            • stiripentol

              stiripentol, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

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

            • tamsulosin

              pseudoephedrine decreases effects of tamsulosin by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • tapentadol

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

            • terazosin

              pseudoephedrine decreases effects of terazosin by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • terbutaline

              terbutaline and pseudoephedrine 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, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

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

            • thiothixene

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

            • tinidazole

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

            • trifluoperazine

              trifluoperazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

            • topiramate

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

            • tramadol

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

            • trazodone

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

            • triazolam

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

            • triclofos

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

            • trifluoperazine

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

            • trimipramine

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

            • triprolidine

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

            • valerian

              valerian increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

            • warfarin

              acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

            • xylometazoline

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

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

            Minor (22)

            • 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.

            • 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.

            • ashwagandha

              ashwagandha increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

            • bemiparin

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

            • bivalirudin

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

            • brimonidine

              brimonidine increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • 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 pseudoephedrine 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.

            • 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

              doxylamine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • felbamate

              felbamate 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

            Arrhythmia

            Palpitations

            Convulsion

            Dizziness

            Drowsiness

            Excitability

            Tremor

            Weakness

            Dermatologic rash

            GI disturbances

            Anemia blood dyscrasias (neutropenia, pancytopenia, leukopenia)

            Bilirubin and alkaline phosphatase may increase

            Dry mouth, throat, and nose

            Thickening of mucus in nose or throat

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            Warnings

            Contraindications

            Hypersensitivity to any of the drugs

            Narrow-angle glaucoma

            <2 years of age

            Use of MAO inhibitors within 14 days

            Stenosing peptic ulcer

            Severe hepatic impairment

            Cautions

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

            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 doses, 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
            • 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, hyperreflexia, 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

            Doxylamine

            • May cause CNS depression, which may impair physical and mental activities
            • Caution in asthma, glaucoma, enlarged prostate, cardiovascular disease, respiratory disease, increased intraocular pressure, or thyroid dysfunction
            • May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur
            • CNS effects may be potentiated when used with other sedative drugs or ethanol

            Pseudoephedrine

            • Caution in cardiovascular disease, diabetes mellitus, prostatic hypertrophy and increased intraocular pressure, renal impairment, seizure disorder, thyroid dysfunction, glaucoma, lactation
            • Elderly may be more sensitive to side effects
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            Pregnancy & Lactation

            Pregnancy category: C

            Lacation: excreted in breast milk, use caution

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

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

            Doxylamine: Competitively blocks histamine from binding to H1 receptors; significant antimuscarinic activity and penetrates CNS, which causes pronounced tendency to induce sedation

            Pseudoephedrine: Stimulates the alpha-adrenergic receptors causing bronchodilation & vasoconstriction

            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

            Doxylamine

            Peak plasma time: 2-3 hr

            Half-life: 10-12 hr

            Excretion: Urine

            Metabolism: Liver (CYP450)

            Pseudoephedrine

            Half-Life: 3 hr (children); 9-16 hr (adults)

            Onset: 30 min (decongestant)

            Duration: 3-8 hr

            Peak Plasma

            Time: 1.97 hr

            Concentration: 422 ng/mL

            Metabolism: Liver, by N-demethylation

            Metabolites: Inactive

            Clearance: 7.3-7.6 mL/min/kg

            Excretion: Urine (43-96%)

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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.