Cough, cold symptoms:
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 are limited; the AAP warns against the use of these products for respiratory illnesses in infants and young children (Ref).
Liquid:
Dextromethorphan 5 mg/chlorpheniramine 0.67 mg per 5 mL (eg, Vicks Children's NyQuil Cold and Cough Multi Symptom Relief):
Children 6 to <12 years: Oral: 15 mL every 6 hours as needed. Maximum daily dose: 60 mL per 24 hours (dextromethorphan 60 mg/chlorpheniramine 8 mg per 24 hours).
Children ≥12 years and Adolescents: Oral: 30 mL every 6 hours as needed. Maximum daily dose: 120 mL per 24 hours (dextromethorphan 120 mg/chlorpheniramine 16 mg per 24 hours).
Dextromethorphan 7.5 mg/chlorpheniramine 1 mg per 5 mL (eg, Robitussin Children's Cough-Cold Long Acting):
Children 6 to <12 years: Oral: 10 mL every 6 hours as needed. Maximum daily dose: 40 mL per 24 hours (dextromethorphan 60 mg/chlorpheniramine 8 mg per 24 hours).
Children ≥12 years and Adolescents: Oral: 20 mL every 6 hours as needed. Maximum daily dose: 80 mL per 24 hours (dextromethorphan 120 mg/chlorpheniramine 16 mg per 24 hours).
Dextromethorphan 15 mg/chlorpheniramine 2 mg per 5 mL (eg, Scot-Tussin):
Children ≥12 years and Adolescents: Oral: 10 mL every 6 hours as needed. Maximum daily dose: 40 mL per 24 hours (dextromethorphan 120 mg/chlorpheniramine 16 mg per 24 hours).
Dextromethorphan 18 mg/chlorpheniramine 4 mg per 5 mL (eg, Maxi-Tuss DM):
Children 6 to <12 years: Oral: 2.5 mL every 4 hours as needed. Maximum daily dose: 15 mL per 24 hours (dextromethorphan 54 mg/chlorpheniramine 12 mg per 24 hours).
Children ≥12 years and Adolescents: Oral: 5 mL every 4 hours as needed. Maximum daily dose: 30 mL per 24 hours (dextromethorphan 108 mg/chlorpheniramine 24 mg per 24 hours).
Tablet:
Dextromethorphan 30 mg/chlorpheniramine 4 mg:
Children ≥12 years and Adolescents: Oral: One tablet every 6 hours as needed. Maximum daily dose: 4 tablets per 24 hours (dextromethorphan 120 mg/chlorpheniramine 16 mg per 24 hours).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; however, chlorpheniramine is metabolized via the liver; therefore, a dosage adjustment may be necessary.
(For additional information see "Dextromethorphan and chlorpheniramine: Drug information")
General dosing guidelines; consult specific product labeling.
Cough, cold symptoms: Oral:
Tablet:
Dextromethorphan 30 mg/chlorpheniramine 4 mg: One tablet every 6 hours as needed (maximum: dextromethorphan 120 mg/chlorpheniramine 16 mg every 24 hours).
Liquid:
Dextromethorphan 15 mg/chlorpheniramine 2 mg per 5 mL: 10 mL every 6 hours (maximum: dextromethorphan 120 mg/chlorpheniramine 16 mg every 24 hours).
Dextromethorphan 15 mg/chlorpheniramine 2 mg per 10 mL: 20 mL every 6 hours (maximum: dextromethorphan 120 mg/chlorpheniramine 16 mg every 24 hours).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
See individual agents.
Use with or within 14 days of discontinuing MAO inhibitor; do not use to sedate a child
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
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. Do not exceed pediatric dosing recommendations. Not for OTC use in children <6 years of age.
Dosage form specific issues:
• Phenylalanine: Some products may contain phenylalanine.
Other warnings/precautions:
• Self-medication (OTC use): Patients with glaucoma or prostatic hyperplasia should consult healthcare provider prior to use. Patients with chronic cough (associated with COPD or smoking) and/or productive cough (eg, copious amounts of phlegm) should be evaluated by a healthcare provider prior to use. Ask healthcare provider prior to using with sedatives. If cough does not improve, is accompanied by rash, fever, or headache, or persists >7 days during use, discontinue use and consult a physician. Do not exceed recommended dose.
Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age are 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 using 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Liquid, Oral:
Robitussin Child Cough/Cold LA: Dextromethorphan hydrobromide 7.5 mg and chlorpheniramine maleate 1 mg per 5 mL (118 mL) [contains fd&c red #40 (allura red ac dye), propylene glycol, sodium benzoate]
Robitussin Nighttime Cough: Dextromethorphan hydrobromide 7.5 mg and chlorpheniramine maleate 1 mg per 5 mL (118 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), propylene glycol, sodium benzoate; fruit punch flavor]
Vicks NyQuil Childrens Cld/Cgh: Dextromethorphan hydrobromide 15 mg and chlorpheniramine maleate 2 mg per 15 mL (236 mL) [acetaminophen free, alcohol free, aspirin free; contains fd&c red #40 (allura red ac dye), propylene glycol; cherry flavor]
Syrup, Oral:
Dimetapp Long Act Cough/Cold: Dextromethorphan hydrobromide 7.5 mg and chlorpheniramine maleate 1mg per 5 mL (118 mL [DSC]) [alcohol free; contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), propylene glycol, sodium benzoate]
Tablet, Oral:
Coricidin HBP Cough/Cold: Dextromethorphan hydrobromide 30 mg and chlorpheniramine maleate 4 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake]
Coricidin HBP Cough/Cold: Dextromethorphan hydrobromide 30 mg and chlorpheniramine maleate 4 mg [contains fd&c yellow #6(sunset yellow)alumin lake, sodium benzoate]
Cough & Cold: Dextromethorphan hydrobromide 30 mg and chlorpheniramine maleate 4 mg [decongestant free; contains fd&c yellow #6(sunset yellow)alumin lake]
Tablet Chewable, Oral:
Triaminic Cough/Runny Nose: Dextromethorphan hydrobromide 5 mg and chlorpheniramine maleate 1 mg [scored; contains aspartame, fd&c blue #2 (indigo carm) aluminum lake; cherry flavor]
May be product dependent
Chewable (Triaminic Cough/Runny Nose Oral)
1-5 mg (per each): $0.27
Liquid (Robitussin Child Cough/Cold LA Oral)
1-7.5 mg/5 mL (per mL): $0.05
Liquid (Robitussin Nighttime Cough Oral)
1-7.5 mg/5 mL (per mL): $0.05
Tablets (Coricidin HBP Cough/Cold Oral)
4-30 mg (per each): $0.37
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.
Oral: Administer oral liquids with an accurate measuring device; do not use a household teaspoon (overdosage may occur).
Store at room temperature.
Temporary relief of symptoms associated with the common cold, hay fever (allergic rhinitis), or other upper respiratory allergies and temporary relief of cough due to minor throat and bronchial irritation that may occur with a cold (OTC products: Liquid: FDA approved in ages ≥6 years and adults; Tablets: FDA approved in ages ≥12 years and adults). Note: Approved ages and uses may vary; consult labeling for specific information.
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]).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Refer to individual components.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Agents with Clinically Relevant Anticholinergic Effects: May enhance the adverse/toxic effect of other Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
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
Amantadine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy
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
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 Agents with Clinically Relevant Anticholinergic Effects. 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
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: Agents with Clinically Relevant Anticholinergic Effects 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 Agents with Clinically Relevant Anticholinergic Effects. 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
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects 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
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 (Systemic): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Dimethindene (Systemic). 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
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: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Eluxadoline. 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): Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Agents with Clinically Relevant Anticholinergic Effects 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): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
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
Ipratropium (Nasal): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Isoproterenol: Chlorpheniramine may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy
Itopride: Agents with Clinically Relevant Anticholinergic Effects 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
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: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mavorixafor: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid combination
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 Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects 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: Agents with Clinically Relevant Anticholinergic Effects 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 Agents with Clinically Relevant Anticholinergic Effects. 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
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
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: Agents with Clinically Relevant Anticholinergic Effects 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: Agents with Clinically Relevant Anticholinergic Effects 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 Agents with Clinically Relevant Anticholinergic Effects. 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
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QuiNIDine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. 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: Agents with Clinically Relevant Anticholinergic Effects 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
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
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Tranylcypromine: May enhance the anticholinergic effect of Antihistamines, First Generation. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. 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
Some products may contain phenylalanine and/or sodium.
Refer to individual monographs.
Chlorpheniramine maleate: Antihistamine with H1-receptor activity
Dextromethorphan: A nonopioid antitussive, increases cough threshold by its activity on the medulla oblongata
See individual agents.
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