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Brompheniramine, Dextromethorphan, and Phenylephrine

Index Terms

  • Dextromethorphan, Phenylephrine, and Brompheniramine
  • Phenylephrine, Brompheniramine, and Dextromethorphan

Dosage Forms

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

Elixir, Oral:

Cold/Cough Childrens: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (118 mL) [alcohol free; contains brilliant blue fcf (fd&c blue #1), disodium edta, fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate]

Dimaphen DM Cold/Cough: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (118 mL) [alcohol free, gluten free; contains brilliant blue fcf (fd&c blue #1), edetate disodium, fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate; grape flavor]

Dimaphen DM Cold/Cough Child: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (118 mL [DSC]) [alcohol free, pseudoephedrine free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate; grape flavor]

Liquid, Oral:

Alahist DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL [DSC]) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium; strawberry flavor]

AP-Hist DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium; strawberry flavor]

BroveX PEB DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per 5 mL (473 mL) [alcohol free; contains propylene glycol, saccharin sodium; bubble-gum flavor]

Dimetapp DM Cold/Cough: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (118 mL, 237 mL) [alcohol free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate; grape flavor]

EndaCof-DM: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (473 mL) [alcohol free, sugar free; contains benzoic acid, edetate disodium, fd&c red #40, propylene glycol, saccharin sodium; strawberry flavor]

Glenmax PEB DM: Brompheniramine maleate 2 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium, sodium benzoate, sorbitol; strawberry flavor]

Glenmax PEB DM FORTE: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium, sodium benzoate, sorbitol; fruit flavor]

LoHist-PEB-DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per 5 mL (473 mL [DSC]) [alcohol free, sugar free; contains benzoic acid, edetate disodium, fd&c red #40, propylene glycol, saccharin sodium; bubble-gum flavor]

M-Hist DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium, sodium benzoate, sorbitol; strawberry flavor]

Niva-Hist DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains saccharin sodium, sodium benzoate; strawberry flavor]

Relcof DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains saccharin sodium, sodium benzoate]

Rynex DM: Brompheniramine maleate 1 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (118 mL, 473 mL) [alcohol free, dye free, gluten free, sugar free; contains methylparaben, propylene glycol, propylparaben; tutti-frutti flavor]

TGQ 7.5PEH/4BRM/15DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL) [contains methylparaben, propylene glycol, propylparaben; strawberry flavor]

TL-Hist DM: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 15 mg, and phenylephrine hydrochloride 7.5 mg per 5 mL (473 mL [DSC]) [contains methylparaben, propylene glycol, propylparaben; strawberry flavor]

Generic: Brompheniramine maleate 4 mg, dextromethorphan hydrobromide 20 mg, and phenylephrine hydrochloride 10 mg per 5 mL (473 mL [DSC])

Syrup, Oral:

BPM-DM-Phen: Brompheniramine maleate 2 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 5 mL (473 mL [DSC]) [contains benzoic acid, disodium edta, fd&c red #40, propylene glycol, saccharin sodium; strawberry flavor]

LoHist-DM: Brompheniramine maleate 2 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 5 mL (473 mL) [alcohol free, dye free, gluten free, sugar free; contains methylparaben, propylene glycol, propylparaben; strawberry flavor]

Brand Names: U.S.

  • Alahist DM [OTC] [DSC]
  • AP-Hist DM [OTC]
  • BPM-DM-Phen [OTC] [DSC]
  • BroveX PEB DM [OTC]
  • Cold/Cough Childrens [OTC]
  • Dimaphen DM Cold/Cough Child [OTC] [DSC]
  • Dimaphen DM Cold/Cough [OTC]
  • Dimetapp DM Cold/Cough [OTC]
  • EndaCof-DM [OTC]
  • Glenmax PEB DM FORTE [OTC]
  • Glenmax PEB DM [OTC]
  • LoHist-DM [OTC]
  • LoHist-PEB-DM [OTC] [DSC]
  • M-Hist DM [OTC]
  • Niva-Hist DM [OTC]
  • Relcof DM [OTC]
  • Rynex DM [OTC]
  • TGQ 7.5PEH/4BRM/15DM [OTC]
  • TL-Hist DM [OTC] [DSC]

Pharmacologic Category

  • Alkylamine Derivative
  • Alpha-Adrenergic Agonist
  • Antitussive
  • Decongestant
  • Histamine H1 Antagonist
  • Histamine H1 Antagonist, First Generation

Pharmacology

Brompheniramine: Competes with histamine for H1-receptor sites on effector cells

Dextromethorphan: Decreases the sensitivity of cough receptors and interrupts cough impulse transmission by depressing the medullary cough center through sigma receptor stimulation

Phenylephrine: Stimulates postsynaptic alpha-receptors, resulting in vasoconstriction, which reduces nasal congestion

Use: Labeled Indications

Cough and upper respiratory allergy 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 to sedate or make a child sleep; with or within 14 days of stopping a monoamine oxidase inhibitor (MAO) inhibitor therapy.

Dosing: Adult

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

Brompheniramine 1 mg/dextromethorphan 5 mg/phenylephrine 2.5 mg per 5 mL: 20 mL every 4 to 6 hours (maximum: 120 mL/24 hours)

Brompheniramine 2 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 5 mL: 10 mL every 4 hours (maximum: 60 mL/24 hours)

Brompheniramine 4 mg/dextromethorphan 15 mg/phenylephrine 7.5 mg per 5 mL: 5 mL every 4 hours (maximum: 30 mL/24 hours)

Brompheniramine 4 mg/dextromethorphan 20 mg/phenylephrine 10 mg per 5 mL: 5 mL every 4 hours (maximum: 30 mL/24 hours)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

Children 2 to <6 years: Brompheniramine 1 mg/dextromethorphan 5 mg/phenylephrine 2.5 mg per 5 mL: Rynex DM: 5 mL every 4 hours (maximum: 30 mL/24 hours)

Children 6 to <12 years:

Brompheniramine 1 mg/dextromethorphan 5 mg/phenylephrine 2.5 mg per 5 mL: 10 mL every 4 to 6 hours (maximum: 60 mL/24 hours)

Brompheniramine 2 mg/dextromethorphan 10 mg/phenylephrine 5 mg per 5 mL: 5 mL every 4 hours (maximum: 30 mL/24 hours)

Brompheniramine 4 mg/dextromethorphan 15 mg/phenylephrine 7.5 mg per 5 mL: 2.5 mL every 4 hours (maximum: 15 mL/24 hours)

Brompheniramine 4 mg/dextromethorphan 20 mg/phenylephrine 10 mg per 5 mL: 2.5 mL every 4 hours (maximum: 15 mL/24 hours)

Children ≥12 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

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

Administration

Shake liquid well before use.

Dietary Considerations

Some products may contain sodium.

Storage

Store at room temperature.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. 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

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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. Monitor therapy

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

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

Amphetamines: May diminish the sedative effect of Antihistamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics 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

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

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. 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

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

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

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

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

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. Monitor therapy

Cocaine: 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. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May increase the serum concentration of CYP2D6 Substrates. 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 (e.g., opioids, barbiturates) with concomitant use. 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

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. Avoid combination

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

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. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. 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

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

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

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

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

MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination

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

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

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

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

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

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

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

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. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

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. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. 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 may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

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

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. Monitor therapy

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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

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 using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Exceptions: FluvoxaMINE. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. 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

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

Tetrahydrocannabinol: 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

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the vasopressor effect of Alpha1-Agonists. 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

Adverse Reactions

Also see individual agents.

Frequency not defined: Central nervous system: Drowsiness

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 which require mental alertness (eg, operating machinery or 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.

• GI obstruction: Use with caution in patients with GI obstruction.

• Increased intraocular pressure: Use with caution in patients with increased intraocular pressure or glaucoma.

• Prostatic hyperplasia/urinary obstruction: 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).

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.

• Pediatric: Antihistamines may cause excitation in young children.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• 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), patients with a breathing problem (eg, emphysema or chronic bronchitis), persistent or chronic cough (such as occurs with asthma or smoking) and/or productive cough (eg, excessive amounts of phlegm) should be evaluated by a health care provider prior to use. 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.

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