Pharmacology
Mechanism of Action
Dexchlorpheniramine: Competes with histamine for H1-receptor sites on effector cells in the GI tract, blood vessels, and respiratory tract. Dexchlorpheniramine is the predominant active isomer of chlorpheniramine and is approximately twice as active as the racemic compound (Moreno 2010).
Dextromethorphan: A nonopioid antitussive, increases cough threshold by its activity on the medulla oblongata.
Phenylephrine: Causes vasoconstriction of the arterioles of the nasal mucosa.
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
Contraindications
OTC labeling: When used for self-medication, do not use with or within 2 weeks of stopping MAOI therapy.
Dosage and Administration
Dosing: Adult
Cough and upper respiratory symptoms: Oral: Dexchlorpheniramine 1 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 5 mL: 10 mL every 4 hours (maximum: 60 mL/24 hours)
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Cough and upper respiratory symptoms: Oral:
Children 2 to <6 years of age: Dexchlorpheniramine 1 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 5 mL: 2.5 mL every 4 hours (maximum: 15 mL/24 hours)
Children 6 to <12 years: Dexchlorpheniramine 1 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 5 mL: 5 mL every 4 hours (maximum: 30 mL/24 hours)
Children ≥12 years and Adolescents: Refer to adult dosing.
Storage
Store at 15°C to 30°C (59°F to 86°F).
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Acetaminophen: May increase the serum concentration of Phenylephrine (Systemic). Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification
AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification
Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. 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. Consider therapy modification
Chloroprocaine: May enhance the hypertensive effect of Phenylephrine (Systemic). Monitor therapy
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CloZAPine: May diminish the therapeutic effect of Phenylephrine (Systemic). Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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. Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification
Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Ergot Derivatives: May enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy
Hyaluronidase: May enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
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. Avoid combination
Ioflupane I 123: Phenylephrine (Systemic) may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
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. Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Memantine: NMDA Receptor Antagonists may enhance the adverse/toxic effect of Memantine. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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. Monitor therapy
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. Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
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. Consider therapy modification
Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Parecoxib: May increase the serum concentration of Dextromethorphan. 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). Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy
Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. 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. Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
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. Monitor therapy
QuiNIDine: May increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Consider therapy modification
QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
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. 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. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). 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. Exceptions: FLUoxetine; Isocarboxazid; Linezolid; Methylene Blue; Moclobemide; PARoxetine; Phenelzine; Tranylcypromine. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. 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. Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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. Consider therapy modification
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Tipranavir: May increase the serum concentration of Dextromethorphan. Management: Consider avoiding dextromethorphan in patients taking tipranavir. If combined, monitor closely for increased dextromethorphan effects/toxicities. Consider therapy modification
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
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. Consider therapy modification
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).
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and heart disease).
- Diabetes: Use with caution in patients with diabetes mellitus.
- Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or angle closure glaucoma.
- Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or GU obstruction. Respiratory disease: Use with caution in patients with asthma or other chronic breathing disorders.
- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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).
- Pediatrics: Antihistamines may cause excitation in young children.
Other warnings/precautions:
- Self-medication (OTC use): When used for self-medication (OTC), contact a health care provider before use if you have a breathing problem (eg, emphysema or chronic bronchitis), persistent or chronic cough (such as occurs with asthma or smoking), or cough accompanied by excessive phlegm; Discontinue use and contact a health care provider if cough persists for more than 1 week, tends to recur, or is accompanied by fever, rah or persistent headache; if symptoms do not improve within 7 days or are accompanied by fever or if nervousness, dizziness, or sleeplessness occur.
Pregnancy
Pregnancy Considerations
Refer to individual agents.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience anxiety, trouble sleeping, or fatigue. Have patient report immediately to prescriber difficult urination, fast heartbeat, abnormal heartbeat, severe dizziness, passing out, shortness of breath, tremors, seizures, or blurred vision.
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
