chlorpheniramine/dextromethorphan (OTC)

Brand and Other Names:Children's Robitussin Cough & Cold Long-Acting, St. Joseph Cough & Cold

Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

chlorpheniramine/dextromethorphan

softchew tablet

  • 1mg/5mg

oral syrup

  • (1mg/7.5mg)/5mL
  • (2mg/15mg)/15mL

tablet

  • 4mg/30mg

Cough & Cold

4mg chlorpheniramine/30mg dextromethorphan PO q6hr PRN

Dosage Forms & Strengths

chlorpheniramine/dextromethorphan

softchew tablet

  • 1mg/5mg

oral syrup

  • (1mg/7.5mg)/5mL
  • (2mg/15mg)/15mL

tablet

  • 4mg/30mg

Cough & Cold

<6 years

  • Safety and efficacy not established

6-12 years

  • Syrup: 2 mg chlorpheniramine/15 mg dextromethorphan PO q6hr
  • Softchew tablet: 2 mg chlorpheniramine/10 mg dextromethorphan PO q4-6hr

>12 years

  • 4mg chlorpheniramine/30mg dextromethorphan PO q6hr PRN
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Interactions

Interaction Checker

and chlorpheniramine/dextromethorphan

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            Contraindicated (7)

            • isocarboxazid

              isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.

            • phenelzine

              phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.

            • procarbazine

              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.

            • 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.

            Serious - Use Alternative (55)

            • amitriptyline

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

            • amoxapine

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

            • apalutamide

              apalutamide will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine transdermal

              buprenorphine transdermal and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buspirone

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

            • calcium/magnesium/potassium/sodium oxybates

              chlorpheniramine, 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.

            • desipramine

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

            • desvenlafaxine

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

            • doxepin

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

            • 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.

            • eluxadoline

              chlorpheniramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.

            • escitalopram

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

            • fentanyl

              fentanyl and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl intranasal

              fentanyl intranasal and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl iontophoretic transdermal system

              fentanyl iontophoretic transdermal system and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transdermal

              fentanyl transdermal and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fexinidazole

              fexinidazole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • 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.

            • idelalisib

              idelalisib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • imipramine

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

            • isocarboxazid

              isocarboxazid increases effects of chlorpheniramine 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.

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

            • lonafarnib

              lonafarnib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • 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.

            • memantine

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

            • meperidine

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

            • methylene blue

              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.

            • metoclopramide intranasal

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

            • milnacipran

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

            • 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.

            • olopatadine intranasal

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

            • 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.

            • protriptyline

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

            • selegiline transdermal

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

            • sertraline

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

            • St John's Wort

              dextromethorphan and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • sodium oxybate

              chlorpheniramine, sodium oxybate. 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.

            • tranylcypromine

              tranylcypromine increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine 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. .

            • trazodone

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

            • trimipramine

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

            • tucatinib

              tucatinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • venlafaxine

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

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

            • vilazodone

              dextromethorphan, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • voxelotor

              voxelotor will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (266)

            • 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.

            • acrivastine

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

            • albuterol

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

            • alfentanil

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

            • almotriptan

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

            • alprazolam

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

            • amifampridine

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

            • amisulpride

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

            • amitriptyline

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

            • amobarbital

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

              amobarbital will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amoxapine

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

            • amphetamine

              amphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

            • apomorphine

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

            • arformoterol

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

            • aripiprazole

              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).

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

            • armodafinil

              chlorpheniramine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. 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).

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

            • asenapine transdermal

              asenapine transdermal and chlorpheniramine both increase sedation. Use Caution/Monitor.

            • bupropion

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

            • avapritinib

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

            • azelastine

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

            • baclofen

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

            • belladonna and opium

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

            • belzutifan

              belzutifan will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benperidol

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

            • benzphetamine

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

            • brexanolone

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

            • brexpiprazole

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

            • brimonidine

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

            • brivaracetam

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

            • brompheniramine

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • carbinoxamine

              carbinoxamine and chlorpheniramine both increase sedation. 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

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

            • cenobamate

              cenobamate will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpromazine

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

            • chlorzoxazone

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

            • cinnarizine

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

            • clemastine

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

            • clobazam

              chlorpheniramine, 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

              chlorpheniramine and clomipramine both increase sedation. 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).

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

            • cocaine topical

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

            • codeine

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

            • crofelemer

              crofelemer increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

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

            • cyclobenzaprine

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

            • cyproheptadine

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

            • dabrafenib

              dabrafenib will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dantrolene

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

            • daridorexant

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

            • desflurane

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

            • desipramine

              chlorpheniramine and desipramine both increase sedation. 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

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

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

            • dexmedetomidine

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

            • dextroamphetamine

              dextroamphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextroamphetamine transdermal

              dextromethorphan, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

              dextroamphetamine transdermal, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

            • dextromoramide

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

            • diamorphine

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

            • diazepam

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

            • diazepam intranasal

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

            • diethylpropion

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

            • difelikefalin

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

            • difenoxin hcl

              chlorpheniramine and difenoxin hcl both increase sedation. 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

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • donepezil transdermal

              donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

            • dopamine

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

            • dopexamine

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

            • dosulepin

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

            • doxepin

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

            • doxylamine

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

            • droperidol

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

            • efavirenz

              efavirenz will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • ergotamine

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

            • esketamine intranasal

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

            • estazolam

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

            • ethanol

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

            • etomidate

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

            • fedratinib

              fedratinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              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.

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

            • fentanyl

              fentanyl, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • 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).

            • fentanyl intranasal

              fentanyl intranasal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transdermal

              fentanyl transdermal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transmucosal

              fentanyl transmucosal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • flibanserin

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

            • fluphenazine

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

            • flurazepam

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

            • formoterol

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

            • fosphenytoin

              fosphenytoin will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • frovatriptan

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

            • gabapentin

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

            • ganaxolone

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

            • gepirone

              gepirone and dextromethorphan both increase serotonin levels. Use Caution/Monitor. Monitor for symptoms of serotonin syndrome when gepirone is used gepirone with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinue gepirone and/or concomitant serotonergic drug.

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

            • gotu kola

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

            • 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).

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

            • hawthorn

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

            • 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).

            • hops

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

            • hyaluronidase

              chlorpheniramine 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

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

            • hydroxyzine

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

            • iloperidone

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

              iloperidone increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imipramine

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

            • isoniazid

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

            • L-tryptophan

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

            • isoproterenol

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

            • istradefylline

              istradefylline will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • kava

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

            • ketamine

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

            • ketotifen, ophthalmic

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

            • lasmiditan

              lasmiditan, chlorpheniramine. 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

              lemborexant, chlorpheniramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lenacapavir

              lenacapavir will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • letermovir

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

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

            • levalbuterol

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

            • lithium

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

            • levorphanol

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

            • lisdexamfetamine

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

            • lofepramine

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

            • lofexidine

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

            • loprazolam

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

            • lorazepam

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

            • lormetazepam

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

            • loxapine

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

              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).

            • loxapine inhaled

              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).

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

            • lsd

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

            • lurasidone

              lurasidone, chlorpheniramine. 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

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

            • marijuana

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

            • metaxalone

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

            • methadone

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

            • methamphetamine

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

            • methocarbamol

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

            • methylenedioxymethamphetamine

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

            • midazolam

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

            • midazolam intranasal

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

            • midodrine

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

            • mirtazapine

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

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

            • mitotane

              mitotane decreases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • 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).

            • modafinil

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

            • morphine

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

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

            • motherwort

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

            • naratriptan

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

            • moxonidine

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

            • nabilone

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

            • nalbuphine

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

            • norepinephrine

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

            • nortriptyline

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

            • olanzapine

              chlorpheniramine 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).

            • opium tincture

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

            • 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).

            • orphenadrine

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

            • oxazepam

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

            • oxycodone

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

            • oxymorphone

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

            • paliperidone

              chlorpheniramine and paliperidone both increase sedation. 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

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

            • papaverine

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

            • passion flower

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

            • 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

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

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

            • pentobarbital

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

            • 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).

            • perphenazine

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

            • phendimetrazine

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

            • phenelzine

              phenelzine increases effects of chlorpheniramine 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

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

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

            • pholcodine

              chlorpheniramine and pholcodine both increase sedation. 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).

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

            • pirbuterol

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

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

            • primidone

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

            • prochlorperazine

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

            • promethazine

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

            • propofol

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

            • propylhexedrine

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

            • protriptyline

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

            • quazepam

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

            • quetiapine

              chlorpheniramine 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

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

            • risperidone

              chlorpheniramine 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.

            • rucaparib

              rucaparib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • 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.

            • salmeterol

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

            • scullcap

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

            • secobarbital

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

            • sevoflurane

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

            • shepherd's purse

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

            • stiripentol

              stiripentol, chlorpheniramine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil

              chlorpheniramine 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

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

            • tazemetostat

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

            • tecovirimat

              tecovirimat will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • temazepam

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

            • terbutaline

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

            • thioridazine

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

            • thiothixene

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

              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).

            • topiramate

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

            • tramadol

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

            • tramadol

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

            • trazodone

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

            • triazolam

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

            • triclofos

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

            • trifluoperazine

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

              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).

            • trimipramine

              chlorpheniramine 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

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

            • valerian

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

            • xylometazoline

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

            • yohimbine

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

            • ziconotide

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

            • ziprasidone

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

            • zolmitriptan

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

            • zotepine

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

            Minor (32)

            • acetazolamide

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

            • amiodarone

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

            • anastrozole

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

            • asenapine

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

            • ashwagandha

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

            • brimonidine

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

            • celecoxib

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

            • chloroquine

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

            • cimetidine

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

            • cyclophosphamide

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

            • darifenacin

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

            • diphenhydramine

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

            • dronedarone

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

            • eucalyptus

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

            • haloperidol

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

            • imatinib

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

            • larotrectinib

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

            • levoketoconazole

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

            • 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.

            • nettle

              nettle increases effects of chlorpheniramine 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.

            • 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.

            • propafenone

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

            • ribociclib

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

            • ritonavir

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

            • sage

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

            • Siberian ginseng

              Siberian ginseng increases effects of chlorpheniramine 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.

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            Adverse Effects

            Frequency Not Defined

            Sedation ranging from mild drowsiness to deep sleep

            CNS depression

            Excitability may occur in children

            Dizziness

            Impaired coordination

            Muscular weakness

            Anorexia

            Nausea

            Vomiting

            Urinary retention

            Blurred vision

            Xerostomia

            Restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitations, seizures reported infrequently

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            Warnings

            Contraindications

            Hypersensitivity

            Within 2 wk of taking a monoamine oxidase (MAO) inhibitor

            Sedation of children

            Cautions

            Ask healthcare professional if trouble urinating due to enlarged prostate gland, history of glaucoma, experiencing a cough that occurs with too much phlegm (mucus), experiencing breathing problems or chronic cough that lasts or as occurs with smoking, asthma, chronic bronchitis or emphysema

            If taking sedatives or tranquilizers, ask healthcare professional

            Do not use more than directed

            Marked drowsiness may occur; use caution when driving a motor vehicle or operating machinery

            Avoid alcoholic drinks

            Alcohol, sedatives, and tranquilizers may increase drowsiness

            Excitability may occur, especially in children

            Discontinue use and ask a healthcare professional if cough lasts more than 7 days, comes back, or is accompanied by fever, rash, or persistent headache as these could be signs of a serious condition

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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: Unknown whether distributed in breast milk, caution advised

            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

            Chlorpheniramine: Histamine H1-receptor antagonist; sedative effect is low; antihistamine and anticholinergic activity is moderate

            Dextromethorphan: Antitussive; derivative of levorphanol; acts on cough center in medulla

            Absorption

            Peak Plasma Time: 2-6 hr (chlorpheniramine); 2-3 hr (dextromethorphan)

            Onset: 15-30 min (dextromethorphan)

            Duration: 3-6 hr (dextromethorphan)

            Distribution

            Protein Bound: 69-72% (chlorpheniramine)

            Vd: 2.5-3.2 L/kg (chlorpheniramine)

            Metabolism

            Metabolism: GI mucosa, liver (chlorpheniramine); hepatic P450 enzyme CYP2D6 (dextromethorphan)

            Metabolites: Monodesmethylchlorpheniramine, didesmethylchlorpheniramine

            Elimination

            Half-Life: 12-43 hr (chlorpheniramine); 2-4 hr (extensive dextromethorphan metabolizers); 24 hr (poor dextromethorphan metabolizers)

            Excretion: Predominantly urine (chlorpheniramine and dextromethorphan)

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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.