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Chlorpheniramine, phenylephrine, and dextromethorphan: Drug information

Chlorpheniramine, phenylephrine, and dextromethorphan: Drug information
(For additional information see "Chlorpheniramine, phenylephrine, and dextromethorphan: Patient drug information" and see "Chlorpheniramine, phenylephrine, and dextromethorphan: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Balamine DM [OTC] [DSC];
  • Ed A-Hist DM [OTC];
  • Ed-A-Hist DM [OTC];
  • Maxichlor PEH DM [OTC];
  • NeoTuss Plus [DSC];
  • NoHist-DM [OTC]
Pharmacologic Category
  • Alkylamine Derivative;
  • Alpha-Adrenergic Agonist;
  • Antitussive;
  • Decongestant;
  • Histamine H1 Antagonist;
  • Histamine H1 Antagonist, First Generation
Dosing: Adult

Note: All dosing is presented in terms of chlorpheniramine maleate/phenylephrine hydrochloride/dextromethorphan hydrobromide.

Cough and upper respiratory symptoms

Cough and upper respiratory symptoms: Oral: Dosing may vary by product; consult specific product labeling.

Liquid: Chlorpheniramine 2 to 4 mg/phenylephrine 5 to 10 mg/dextromethorphan 12.5 to 15 mg per 5 mL: 5 mL every 4 to 6 hours (maximum: 30 mL/24 hours).

Tablet:

Chlorpheniramine 4 mg/phenylephrine 10 mg/dextromethorphan 10 mg: One tablet every 4 hours (maximum: 6 tablets/24 hours).

Chlorpheniramine 4 mg/phenylephrine 10 mg/dextromethorphan 18 mg: One tablet every 4 hours (maximum: 6 tablets/24 hours).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Chlorpheniramine, phenylephrine, and dextromethorphan: Pediatric drug information")

Note: Multiple concentrations of oral liquid formulations exist; close attention must be paid to the concentration when ordering or administering. Safety and efficacy for the use of cough and cold products in infants and young children is limited; the AAP warns against the use of these products for respiratory illnesses in infants and young children; the FDA does not recommend OTC use in infants and children <2 years of age due to the risk of serious and life-threatening adverse effects (including death) and recommends to use with caution in pediatric patients ≥2 years of age (Ref).

Cough and upper respiratory symptoms

Cough and upper respiratory symptoms: Dosing may vary by product; consult specific product labeling.

Liquid:

Chlorpheniramine 4 mg/phenylephrine 10 mg/dextromethorphan 15 mg per 5 mL (eg, Ed A-Hist DM liquid, NoHist DM): Oral:

Children 6 to <12 years: 2.5 mL every 4 hours as needed. Maximum daily dose: 15 mL/24 hours.

Children ≥12 years and Adolescents: 5 mL every 4 hours as needed. Maximum daily dose: 30 mL/24 hours.

Chlorpheniramine 2 mg/phenylephrine 5 mg/dextromethorphan 5 mg per 15 mL (eg, Father John's Medicine Plus): Oral: Children ≥12 years and Adolescents: 30 mL every 4 hours as needed. Maximum daily dose: 180 mL/24 hours.

Tablets:

Chlorpheniramine 4 mg/phenylephrine 10 mg/dextromethorphan 10 mg per tablet (eg, Ed Hist-A DM tablets): Oral:

Children 6 to <12 years: 1/2 tablet every 4 hours as needed. Maximum daily dose: 3 tablets/24 hours.

Children ≥12 years and Adolescents: 1 tablet every 4 hours as needed. Maximum daily dose: 6 tablets/24 hours.

Chlorpheniramine 4 mg/phenylephrine 10 mg/dextromethorphan 18 mg per tablet (eg, Maxichlor): Oral:

Children 6 to <12 years: 1/2 tablet every 4 hours as needed. Maximum daily dose: 3 tablets/24 hours.

Children ≥12 years and Adolescents: 1 tablet every 4 hours as needed. Maximum daily dose: 6 tablets/24 hours.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

See individual agents.

Contraindications

OTC labeling: When used for self-medication, do not use with or within 14 days of monoamine oxidase inhibitor therapy or to sedate a child.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

Special populations:

• CYP2D6 poor metabolizers: Dextromethorphan is metabolized by hepatic CYP2D6. Poor metabolizers of CYP2D6 may have exaggerated or prolonged effects of dextromethorphan. Increased risk may be seen with concomitant use of potent CYP2D6 inhibitors; use with caution (Abduljalil 2010; Jurica 2012; Sager 2014; Zhou 2009).

• Pediatric: Antihistamines may cause excitation in young children.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider prior to use if you have breathing problems (eg, chronic bronchitis, emphysema), persistent or chronic cough (such as occurs with asthma or smoking), productive cough (eg, excessive amounts of phlegm), diabetes, glaucoma, heart disease, high BP, thyroid disease, difficultly in urination due to enlargement of the prostate gland, or are currently taking sedatives, tranquilizers, or other oral nasal decongestants or stimulants. Discontinue use and notify health care provider if new symptoms occur, if symptoms do not improve within 7 days or are accompanied by fever, rash, or persistent headache, or if nervousness, dizziness, or sleeplessness occur.

Warnings: Additional Pediatric Considerations

Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; the AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported (in some cases, high blood concentrations of pseudoephedrine were found). Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. The FDA does not recommend OTC uses for these products in pediatric patients <2 years of age and recommends to use with caution in pediatric patients ≥2 years of age. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018; CDC 2007; FDA 2017; FDA 2018). Antihistamines should not be used to make an infant or child sleepy. Multiple concentrations of oral liquid formulations exist; close attention must be paid to the concentration when ordering or administering.

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Oral:

Ed-A-Hist DM: Chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 10 mg, and dextromethorphan hydrobromide 15 mg per 5 mL (473 mL) [gluten free, sugar free; contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow), methylparaben, propylene glycol, propylparaben; banana flavor]

NeoTuss Plus: Chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 7.5 mg, and dextromethorphan hyrobromide 30 mg per 5 mL (474 mL [DSC]) [alcohol free, codeine free, dye free, sugar free; contains methylparaben, propylene glycol, propylparaben; cherry flavor]

NoHist-DM: Chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 10 mg, and dextromethorphan hydrobromide 15 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains edetate (edta) disodium, methylparaben, propylene glycol, propylparaben, saccharin calcium; grape flavor]

Syrup, Oral:

Balamine DM: Chlorpheniramine maleate 2 mg, phenylephrine hydrochloride 5 mg, and dextromethorphan hydrobromide 10 mg per 5 mL (473 mL [DSC]) [alcohol free, dye free, sugar free; contains sodium benzoate]

Tablet, Oral:

Ed A-Hist DM: Chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 10 mg, and dextromethorphan hydrobromide 10 mg [scored]

Maxichlor PEH DM: Chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 10 mg, and dextromethorphan hydrobromide 18 mg [scored]

Generic Equivalent Available: US

Yes

Pricing: US

Liquid (Gencontuss Oral)

5-2-10 mg/5 mL (per mL): $0.03

Liquid (Giltuss Allergy Cgh&Cong Child Oral)

5-2-10 mg/5 mL (per mL): $0.06

Liquid (Giltuss Allergy Cough & Conges Oral)

5-2-10 mg/5 mL (per mL): $0.06

Tablets (Maxichlor PEH DM Oral)

10-4-18 mg (per each): $0.50

Tablets (Phenagil CH Oral)

10-3.5-29 mg (per each): $0.66

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer liquid with an accurate measuring device; do not use a household teaspoon (overdosage may occur).

Administration: Pediatric

Oral: Administer liquid with an accurate measuring device; do not use a household teaspoon (overdosage may occur).

Use: Labeled Indications

Cough and upper respiratory symptoms: Temporary relief of symptoms (runny nose, sneezing, itchy nose or throat, itchy/watery eyes, cough due to minor throat and bronchial irritation, nasal congestion, nasal passages swelling) associated with the common cold, hay fever (allergic rhinitis), or other upper respiratory allergies.

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Chlorpheniramine, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Atropine (Systemic): May enhance the hypertensive effect of Alpha1-Agonists. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider delaying skin testing until alpha1-agonists are no longer required, or use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Risk D: Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Betahistine may diminish the therapeutic effect of Antihistamines. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromocriptine: May enhance the hypertensive effect of Alpha1-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider therapy modification

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chloroprocaine (Systemic): May enhance the hypotensive effect of Phenylephrine (Systemic). Risk C: Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: Chlorpheniramine may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Hyaluronidase: May enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Iobenguane Radiopharmaceutical Products: Alpha1-Agonists may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Isoproterenol: Chlorpheniramine may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy

Lisuride: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Memantine: NMDA Receptor Antagonists may enhance the adverse/toxic effect of Memantine. Risk C: Monitor therapy

Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: Dextromethorphan may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Parecoxib: May increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Pergolide: May enhance the hypertensive effect of Alpha1-Agonists. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Propacetamol: May increase the serum concentration of Phenylephrine (Systemic). Management: Monitor patients closely for increased side effects of phenylephrine if propacetamol is used concomitantly. Patients with underlying blood pressure issues or arrhythmias may need closer monitoring and may warrant consideration of alternative therapies. Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Dextromethorphan may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. The dose of dextromethorphan/bupropion product should not exceed 1 tablet once daily. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

Serotonergic Agents (High Risk): Dextromethorphan may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: Chlorpheniramine may enhance the arrhythmogenic effect of Thioridazine. Thioridazine may increase the serum concentration of Chlorpheniramine. Management: Avoid this combination when possible. If used, monitor closely for arrhythmia as well as general toxicity of chlorpheniramine. Risk D: Consider therapy modification

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Pregnancy Considerations

Refer to individual monographs.

Breastfeeding Considerations

Refer to individual monographs.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Codilar;
  • (DO) Dominican Republic: Gritos EX | Tusilac;
  • (EG) Egypt: Codilar;
  • (GM) Gambia: Makoff baby;
  • (IN) India: Active dm | Alercom d | Alex cough | Alkof junior | Alvikoff dx | Ambrolite d plus | Aroget dx | Arokuf dm | Ascoril d plus | Asthakind DX | Ataque d | Axahem d | Banocof d | Besto-Cof | Brokam dx | Broncosip dx | Bronkolyte dx | Brucuf dx | Cadicoff d | Catarex at | Cheridryl | Citikof dx | Cofaid d | Cofheal D | Cofsy dx | Coldex dx | Corid | Cotuss | Cough-x | Cozymin dx | Deletus d plus | Diafree | Drycoff | Ericuf d | Exit dx | Extus dmr | Gerituss D | Gracof plus | Helpotus dx | Ibikof | Iphardin d | Kazicof dx | Kep d | Kidylinctus d | Kofkul | Kofrid d | Kufgen d | Kufril D | Larycof d | Libitus | Nemtus d | New torex junior | Novocoff | Orange cs | Otus | Piritexyl plus | Respicure d | Respihop d | Ridkof | Saloxen | Sdkoff | Silicof d | Silkof | Solvin dx | Spurex xt | Timaxx d | Tixylix d | Tusq dx | Welminic dx | Xpect d | Xrate dx | Zeet dx | Zyrcold dc;
  • (KE) Kenya: Chericof cough formula | Contus paediatric | Cosome cough | Eascof d | Rinovil d | Sputac d | Tusq dx;
  • (MY) Malaysia: Windexco pe;
  • (PE) Peru: Chericof | Neo silenai | Neo silenai pediatrico;
  • (PR) Puerto Rico: Bio b kids | Bio rytuss | Bronkids | Ceron DM | Cerose dm | Corfen-dm | De-chlor dm | Ed a hist dm | Gencontuss | Giltuss allergy plus cough & congestion | Neo DM | Nohist dm | Nohist-Pdx | Norel cs | Norel dm | Pancof | Pe-Hist DM | Phenabid dm | Tri vent dpc | Trital dm | Trituss dm | Tussilan Cl | Zotex 12d;
  • (PY) Paraguay: Bronalar nf | Metosfan n.f. | Tecnogrip bb;
  • (RU) Russian Federation: Therasil D;
  • (SA) Saudi Arabia: Codilar;
  • (TH) Thailand: Dexchlophen | Fercof;
  • (UG) Uganda: Contus paediatric | Koff go;
  • (ZM) Zambia: Contus paed linctus
  1. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
  2. Abduljalil K, Frank D, Gaedigk A, et al. Assessment of activity levels for CYP2D6*1, CYP2D6*2, and CYP2D6*41 genes by population pharmacokinetics of dextromethorphan. Clin Pharmacol Ther. 2010;88(5):643-651. doi: 10.1038/clpt.2010.137. [PubMed 20881950]
  3. American Academy of Pediatrics (AAP). Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. Updated June 12, 2018. Available at http://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/
  4. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  5. Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56(1):1-4. [PubMed 17218934]
  6. Ed A-Hist DM (chlorpheniramine maleate/dextromethorphan hydrobromide/phenylephrine hydrochloride liquid) [prescribing information]. Ripley, MS: Edwards Pharmaceuticals, Inc.; February 2013.
  7. Ed A-Hist DM (chlorpheniramine maleate/dextromethorphan hydrobromide/phenylephrine hydrochloride tablet) [prescribing information]. Ripley, MS: Edwards Pharmaceuticals; March 2017.
  8. Food and Drug Administration (FDA). Most young children with a cough or cold don't need medicines. July 18, 2017. Available at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm. Last accessed November 2, 2018.
  9. Food and Drug Administration (FDA). Use caution when giving cough and cold products to kids. Updated February 8, 2018. Available at https://www.fda.gov/drugs/resourcesforyou/specialfeatures/ucm263948.htm. Last accessed November 2, 2018.
  10. Jurica J, Bartecek R, Zourkova A, et al. Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice. J Clin Pharm Ther. 2012;37(4):486-490. doi: 10.1111/j.1365-2710.2012.01333.x. [PubMed 22548589]
  11. Maxichlor PEH DM (chlorpheniramine maleate/dextromethorphan hydrobromide/phenylephrine hydrochloride tablet) [prescribing information]. Brooksville, FL: MCR American Pharmaceuticals; February 2018.
  12. NoHist DM (chlorpheniramine maleate/dextromethorphan hydrobromide/phenylephrine hydrochloride liquid) [prescribing information]. Canton, MS: Larken Laboratories; July 2016.
  13. NoHist DM (chlorpheniramine maleate/dextromethorphan hydrobromide/phenylephrine hydrochloride liquid) [prescribing information]. Canton, MS: Larken Laboratories; November 2018.
  14. Sager JE, Lutz JD, Foti RS, et al. Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4. Clin Pharmacol Ther. 2014;95(6):653-662. doi: 10.1038/clpt.2014.50. [PubMed 24569517]
  15. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  16. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. doi:10.1111/j.1525-139X.2007.00280.x [PubMed 17555487]
  17. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet. 2009;48(12):761-804. doi: 10.2165/11318070-000000000-00000. [PubMed 19902987]
Topic 8865 Version 298.0

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