acetaminophen/doxylamine/dextromethorphan/phenylephrine (OTC)

Brand and Other Names:Alka-Seltzer Plus Night Cold Formula, Tylenol Cold Multi-Symptom Nighttime Liquid, more...Alka-Seltzer Plus Night Severe Cold, Cough & Flu, Alka-Seltzer Plus Night Sinus Congestion, Allergy & Cough
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

acetaminophen/doxylamine/dextromethorphan/phenylephrine

capsule

  • 325mg/6.25mg/10mg/5mg

Congestion, Rhinorrhea, Cough, Sore Throat, Headache, Fever, Minor Aches & Pains

2 caps PO q4hr PRN; not to exceed 12 caps/day

Dosage Forms & Strengths

acetaminophen/doxylamine/dextromethorphan/phenylephrine

capsule

  • 325mg/6.25mg/10mg/5mg

Congestion, Rhinorrhea, Cough, Sore Throat, Headache, Fever, Minor Aches & Pains

<12 Years

  • Ask a pediatrician

≥12 Years

  • 2 caps PO q4hr PRN; not to exceed 12 caps/day
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Interactions

Interaction Checker

and acetaminophen/doxylamine/dextromethorphan/phenylephrine

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            Contraindicated (11)

            • 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 and dextromethorphan both increase serotonin levels. Contraindicated.

              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 and dextromethorphan both increase serotonin levels. Contraindicated.

            • 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.

              procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • rasagiline

              rasagiline and dextromethorphan both increase serotonin levels. Contraindicated. Risk of psychosis episodes or bizarre behavior.

            • selegiline transdermal

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

            • safinamide

              dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.

            • selegiline

              selegiline and dextromethorphan both increase serotonin levels. Contraindicated.

            • tranylcypromine

              tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.

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

            Serious - Use Alternative (54)

            • amitriptyline

              amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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 and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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.

            • 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.

            • buspirone

              buspirone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • cabergoline

              cabergoline, phenylephrine. 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.

            • citalopram

              citalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clomipramine

              clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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 and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • desvenlafaxine

              dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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 and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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.

            • duloxetine

              duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • escitalopram

              escitalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • 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.

            • fluoxetine

              fluoxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              fluoxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit will increase the level or effect of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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 and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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.

            • 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. .

            • levomilnacipran

              levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • isoflurane

              isoflurane increases toxicity of phenylephrine 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.

            • linezolid

              linezolid and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • 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.

              lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • lorcaserin

              dextromethorphan and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • maprotiline

              maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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.

            • memantine

              memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • methoxyflurane

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

            • meperidine

              dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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

              methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • methylergonovine

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

            • milnacipran

              milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • nefazodone

              nefazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              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.

            • paroxetine

              paroxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              paroxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • protriptyline

              protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            Monitor Closely (302)

            • 5-HTP

              5-HTP and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • 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

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

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

            • almotriptan

              almotriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • alprazolam

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

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

            • 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.

            • amitriptyline

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

            • amitriptyline

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

            • amobarbital

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

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

            • amoxapine

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

              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 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.

              dextromethorphan, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

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

            • armodafinil

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

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • asenapine

              dextromethorphan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • atogepant

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

            • avapritinib

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

            • axitinib

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

            • azelastine

              azelastine and doxylamine both increase sedation. 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.

            • azelastine

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

            • baclofen

              doxylamine and baclofen both increase sedation. 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.

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

            • benperidol

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

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

            • benzphetamine

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

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

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

            • brexanolone

              brexanolone, doxylamine. Either increases toxicity of the other by sedation. 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.

              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

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

            • buprenorphine buccal

              doxylamine and buprenorphine buccal 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.

            • bupropion

              bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. 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.

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

            • butalbital

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

              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.

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

            • caffeine

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

            • carbinoxamine

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

            • carbinoxamine

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

            • cariprazine

              dextromethorphan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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.

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

            • chlordiazepoxide

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

              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.

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

            • chlorpromazine

              doxylamine and chlorpromazine both increase sedation. 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.

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

            • chlorzoxazone

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

            • cinnarizine

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

            • cinnarizine

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

            • clemastine

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

              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).

              clobazam will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

            • clomipramine

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

            • clozapine

              dextromethorphan, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • clomipramine

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

            • clonazepam

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

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

            • clorazepate

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

            • clozapine

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

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

            • cocaine

              cocaine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • codeine

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

              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.

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

            • cyclobenzaprine

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

            • cyproheptadine

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

            • cyproheptadine

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

            • dantrolene

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

            • dapsone topical

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

            • desipramine

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

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

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

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

            • dexchlorpheniramine

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

            • dexchlorpheniramine

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

            • dexfenfluramine

              dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

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

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

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

            • dexmedetomidine

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

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

            • dextroamphetamine

              dextroamphetamine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • dextromoramide

              doxylamine and dextromoramide both increase sedation. 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

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

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

            • diazepam

              diazepam and doxylamine both increase sedation. 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.

            • 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.

            • difenoxin hcl

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

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

            • dihydroergotamine

              dextromethorphan and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine intranasal

              dextromethorphan and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dimenhydrinate

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

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

            • diphenhydramine

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

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

            • diphenoxylate hcl

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

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

            • dipipanone

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

              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.

            • dopexamine

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

            • dosulepin

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

            • doxepin

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

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

            • droperidol

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

              doxylamine and droperidol both increase sedation. 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

            • eletriptan

              eletriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eltrombopag

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

            • ergotamine

              dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • esketamine intranasal

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

            • 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.

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

            • ethanol

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

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

            • etomidate

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

              fenfluramine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

              dextromethorphan and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • fenfluramine

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

            • fluphenazine

              dextromethorphan, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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 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.

            • frovatriptan

              frovatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • haloperidol

              dextromethorphan, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • iloperidone

              dextromethorphan, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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.

              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.

            • 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.

            • gotu kola

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

            • haloperidol

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

              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.

            • hydralazine

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

            • 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. .

            • hydromorphone

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

              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.

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

            • iloperidone

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

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

            • imipramine

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

              doxylamine and imipramine both increase sedation. 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.

            • isavuconazonium sulfate

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

            • isoniazid

              dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • L-tryptophan

              dextromethorphan and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • 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.

            • 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.

            • ketamine

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

            • ketotifen, ophthalmic

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

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

            • letermovir

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

            • 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.

              doxylamine and levorphanol both increase sedation. 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.

            • lithium

              dextromethorphan and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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

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

            • 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.

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

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

            • lorazepam

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

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

            • lormetazepam

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

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

            • loxapine

              dextromethorphan, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

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

              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.

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

              dextromethorphan, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lsd

              dextromethorphan and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • lumefantrine

              lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lurasidone

              dextromethorphan, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • maprotiline

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

            • maprotiline

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

            • marijuana

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

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

            • melatonin

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

              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.

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

            • meprobamate

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

              doxylamine and meprobamate both increase sedation. 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.

            • metaxalone

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

            • methadone

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

              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.

            • methocarbamol

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

            • methyldopa

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

            • methylenedioxymethamphetamine

              methylenedioxymethamphetamine and phenylephrine 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.

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

            • midazolam

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

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

              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

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

              dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

              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.

            • molindone

              dextromethorphan, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • morphine

              dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • morphine

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

            • naratriptan

              naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • motherwort

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

              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.

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

            • nabilone

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

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

            • nadolol

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

            • nalbuphine

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

            • 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.

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

            • olanzapine

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

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

              dextromethorphan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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.

            • paliperidone

              dextromethorphan, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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

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

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

            • orphenadrine

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

            • oxazepam

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

            • oxazepam

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

            • oxycodone

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

              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

              doxylamine and oxymorphone both increase sedation. 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

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

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

            • panobinostat

              panobinostat will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

            • papaveretum

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

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

            • papaverine

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

            • pazopanib

              pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, dextromethorphan. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • passion flower

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

            • perphenazine

              dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pentazocine

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

            • pentobarbital

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

              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.

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

            • 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.

            • 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.

              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.

            • phenylephrine PO

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

            • pholcodine

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

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

            • pimavanserin

              dextromethorphan, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimozide

              dextromethorphan, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

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

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

            • pindolol

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

            • quetiapine

              dextromethorphan, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • 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.

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

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

            • prochlorperazine

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

              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 and doxylamine both increase sedation. Use Caution/Monitor.

            • 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.

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

            • propranolol

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

            • propylhexedrine

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

            • 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

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

              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 and doxylamine both increase sedation. 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.

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

            • quinidine

              quinidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ramelteon

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

            • rasagiline

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

            • 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

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

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

              dextromethorphan, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • rizatriptan

              rizatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • rolapitant

              rolapitant will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor for adverse reactions when unable to avoid coadministration with narrow therapeutic index CYP2D6 substrates.

            • SAMe

              dextromethorphan and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • scullcap

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

            • 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.

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

            • selegiline

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

            • sevoflurane

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

            • shepherd's purse

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

              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.

            • 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

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

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

            • sumatriptan

              sumatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tapentadol

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

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

              temazepam and doxylamine both increase sedation. 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

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

            • 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

              dextromethorphan, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

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

              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).

            • tramadol

              dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tinidazole

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

            • topiramate

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

            • topiramate

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

            • tramadol

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

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

            • trazodone

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

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

            • triazolam

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

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

            • triclofos

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

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

            • trifluoperazine

              dextromethorphan, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

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

              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.

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

            • ziprasidone

              dextromethorphan, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • triprolidine

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

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

            • zolmitriptan

              zolmitriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (84)

            • 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.

            • amiodarone

              amiodarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • antithrombin alfa

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

            • antithrombin III

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

            • argatroban

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

            • asenapine

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

              asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ashwagandha

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

            • celecoxib

              celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • bemiparin

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

            • bivalirudin

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

            • 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.

            • chloroquine

              chloroquine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cholestyramine

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

            • cimetidine

              cimetidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • darifenacin

              darifenacin will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • diphenhydramine

              diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • 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.

            • dronedarone

              dronedarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 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

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

              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.

            • 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).

            • haloperidol

              haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • heparin

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

            • imatinib

              imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • maraviroc

              maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • 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.

            • nettle

              nettle increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

            • nilotinib

              nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

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

            • oxybutynin

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

            • oxybutynin topical

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

            • oxybutynin transdermal

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

            • parecoxib

              parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • phenindione

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

            • phenobarbital

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

            • 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.

            • propafenone

              propafenone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • protamine

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

            • quinacrine

              quinacrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • rifabutin

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

            • rifampin

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

            • ritonavir

              ritonavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • 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.

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

            • Siberian ginseng

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

            • sertraline

              sertraline will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • thioridazine

              thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tiagabine

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

            • tipranavir

              tipranavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

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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

            GI disturbances

            Anemia blood dyscrasias (neutropenia, pancytopenia, leukopenia)

            Bilirubin & alkaline phosphatase may increase

            Dry mouth, throat, and nose

            Thickening of mucus in nose or throat

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            Warnings

            Contraindications

            Hypersensitivity

            Asthma

            Narrow-angle glaucoma

            Symptomatic prostate hypertrophy

            Bladder-neck obstruction

            Stenosing peptic ulcer

            G-6-PD deficiency

            Severe hepatic impairment

            Cautions

            Acetaminophen hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness

            Acetaminophen contained in many OTC products & combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose

            Do not take dextromethorphan 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

            Dextromethorphan may slow respiration rate

            Doxylamine may exacerbate angle closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur

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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: 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

            Acetaminophen: 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

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

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

            Phenylephrine is a 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

            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

            Doxylamine

            • Peak plasma time: 2-3 hr
            • Half-life: 10-12 hr
            • Excretion: Urine
            • Metabolism: Liver (CYP450)
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            Images

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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.