Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DELSYM vs DEXTROMETHORPHAN POLISTIREX
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist, which suppresses cough by elevating the threshold for coughing in the medullary cough center.
Dextromethorphan polistirex is an NMDA receptor antagonist and sigma-1 receptor agonist. It inhibits serotonin reuptake and acts on the brain stem cough center to elevate the threshold for coughing.
Symptomatic relief of cough caused by minor throat and bronchial irritation
Symptomatic relief of nonproductive cough associated with upper respiratory tract infections,Off-label: Management of pseudobulbar affect (with quinidine),Off-label: Treatment of neuropathic pain
60 mg orally every 12 hours (extended-release suspension).
30-60 mg orally every 12 hours; not to exceed 120 mg in 24 hours.
Terminal elimination half-life of dextromethorphan is approximately 11 hours (range 9-14 hours) in extensive metabolizers; in poor metabolizers (CYP2D6 deficiency), half-life can exceed 24 hours, leading to accumulation.
Terminal half-life: 13–19 hours; clinical context: extended-release formulation due to polistirex complex; time to steady-state: ~3 days
Metabolized primarily by CYP2D6 to dextrorphan, an active metabolite; also undergoes O-demethylation and N-demethylation.
Hepatic via CYP2D6 (O-demethylation to dextrorphan, active metabolite). Also undergoes N-demethylation via CYP3A4. Polymorphic metabolism (poor metabolizers at risk of toxicity).
Renal excretion of unchanged drug and metabolites, primarily dextrorphan glucuronide; <5% excreted unchanged in urine. Biliary/fecal elimination is negligible.
Renal: ~45% as unchanged drug and metabolites (dextrorphan conjugates); fecal: <2%; biliary: minimal
~45-50% bound to plasma albumin; main binding protein is albumin.
~50% bound; primarily to albumin
5-6 L/kg, indicating extensive tissue distribution.
Vd: ~5–6 L/kg; clinical meaning: extensive tissue distribution, including CNS
Oral: ~10-25% due to extensive first-pass metabolism (CYP2D6 and CYP3A4); bioavailability is higher in poor metabolizers.
Oral (polistirex): approximately 50–60% (first-pass metabolism reduces systemic availability)
No dose adjustment recommended for mild-to-moderate renal impairment; safety in severe renal impairment not established.
No specific dosing adjustment provided for dextromethorphan polistirex; use with caution in severe renal impairment (Cr Cl < 30 m L/min) due to potential accumulation of metabolites.
No dose adjustment recommended for mild-to-moderate hepatic impairment; safety in severe hepatic impairment not established.
No specific dosing adjustment provided; use with caution in severe hepatic impairment (Child-Pugh class C) due to reduced clearance.
Children 6-11 years: 30 mg orally every 12 hours. Children 12 years and older: 60 mg orally every 12 hours. Do not exceed 60 mg in 24 hours for ages 6-11 or 120 mg for ages 12+.
Children 6-12 years: 15-30 mg orally every 12 hours; not to exceed 60 mg in 24 hours. Children 2-5 years: 7.5-15 mg orally every 12 hours; not to exceed 30 mg in 24 hours. Not recommended under 2 years.
Start at low end of dosing range; monitor for anticholinergic effects and sedation. No specific dose adjustment in elderly but caution due to increased sensitivity.
Elderly patients may be more sensitive to anticholinergic effects; use the lowest effective dose and monitor for adverse effects such as sedation and dizziness.
None
No FDA black box warning.
Do not use in children under 4 years of age,Avoid use with MAO inhibitors or for 2 weeks after stopping,Chronic use may lead to dependence and abuse,Caution in patients with respiratory depression, asthma, or chronic obstructive pulmonary disease
Do not use with MAOIs or within 14 days of stopping MAOIs,Risk of serotonin syndrome when used with serotonergic drugs,Caution in patients with G6PD deficiency, hepatic impairment, or chronic cough associated with smoking, asthma, or emphysema,QT prolongation risk at supratherapeutic doses,Misuse potential with high doses causing dissociative effects
Hypersensitivity to dextromethorphan or any component,Use with or within 14 days of MAO inhibitors,Use in patients with respiratory depression or severe asthma
Concurrent use or within 14 days of MAOIs,Hypersensitivity to dextromethorphan or any component,Use in children under 2 years of age (OTC products)
No significant food interactions. Avoid grapefruit juice as it may increase dextromethorphan levels. Take with or without food.
Avoid grapefruit and grapefruit juice as they may alter metabolism. Take with or without food; food does not significantly affect absorption.
Category D (positive evidence of human fetal risk): First trimester exposure associated with rare reports of congenital malformations including cardiac defects and oral clefts based on observational studies. Second and third trimester use may cause fetal respiratory depression, bradycardia, and neonatal adaptation syndrome with prolonged use near term. Risks increase with higher doses and chronic use.
No well-controlled studies in pregnant women. Animal studies have not shown evidence of fetal harm. Based on limited human data, risk of major congenital malformations is low. Avoid use in first trimester due to theoretical risk based on weak NMDA antagonism.
Excreted into breast milk in low concentrations (M/P ratio 0.1–0.4). Considered compatible with breastfeeding by American Academy of Pediatrics; however, monitor infant for drowsiness, respiratory depression, and poor feeding. Avoid if infant is premature or has respiratory compromise. Use shortest duration possible.
Limited data; excreted in human breast milk in low amounts (M/P ratio not established). Theoretical risk of CNS depression in infant. Use with caution, especially in neonates or preterm infants. Consider immediate-release formulations if necessary.
No pharmacokinetic studies show significant changes in dextromethorphan clearance during pregnancy. Therefore, no empiric dose adjustment is recommended. However, because of increased plasma volume and renal blood flow in pregnancy, the duration of action may be shorter, requiring more frequent dosing if clinically indicated. Use lowest effective dose for shortest duration.
No specific dose adjustments recommended for pregnancy; however, use lowest effective dose due to altered pharmacokinetics (increased volume of distribution, decreased plasma protein binding) potentially leading to reduced peak concentrations but unchanged half-life.
DELSYM (dextromethorphan polistirex) is a sustained-release formulation providing up to 12 hours of cough suppression. Do not crush or chew capsules; swallow whole. Avoid use in patients with asthma, COPD, or respiratory insufficiency due to risk of respiratory depression. Contraindicated with MAOIs and within 14 days of MAOI use due to serotonin syndrome risk. Not recommended for chronic cough or cough associated with excessive secretions. Use caution in patients with G6PD deficiency (rare hemolysis risk).
Dextromethorphan polistirex is an extended-release formulation allowing twice-daily dosing. Its antitussive effect lasts up to 12 hours. Caution in patients with asthma or COPD as it may reduce mucociliary clearance. Avoid concurrent use with MAOIs due to risk of serotonin syndrome. Not effective for chronic cough and should not be used for more than 7 days.
Take DELSYM only as directed for temporary cough relief.,Swallow capsules whole; do not crush, chew, or dissolve.,Do not exceed recommended dose or use for more than 7 days unless directed by a doctor.,Avoid alcohol while taking this medication.,Do not use if you are taking or have taken a monoamine oxidase inhibitor (MAOI) within the last 14 days.,Seek medical attention if cough persists, comes with fever, rash, or headache, or if you experience signs of serotonin syndrome (agitation, hallucinations, rapid heart rate, fever, muscle stiffness).,Keep out of reach of children; accidental overdose may cause death.
Do not crush or chew the extended-release capsules or suspension; swallow whole or shake suspension well before use.,Do not exceed recommended doses; may cause drowsiness, avoid driving or operating machinery.,Discontinue use and consult healthcare provider if cough persists more than 7 days or is accompanied by fever, rash, or headache.,Avoid alcohol and other CNS depressants as they may increase sedation.,Inform healthcare provider if you are taking MAOIs (e.g., for depression, Parkinson's) or SSRIs to avoid serotonin syndrome.,Keep out of reach of children; overdose can be fatal.
No interactions on record
"The combination of dextromethorphan, a centrally acting antitussive with NMDA receptor antagonist and sigma-1 receptor agonist properties, and aceprometazine, a phenothiazine neuroleptic with strong antihistaminergic and moderate anticholinergic and antidopaminergic effects, can result in additive central nervous system depression. This interaction may lead to excessive sedation, respiratory depression, impaired psychomotor function, and an increased risk of falls or cognitive impairment, particularly in elderly or debilitated patients. Concurrent use may also lower the seizure threshold, especially in patients with predisposing factors."
"Dextromethorphan, a serotonergic agent metabolized by CYP2D6, when combined with cariprazine, a dopamine D3/D2 receptor partial agonist, may increase the risk of serotonin syndrome due to additive serotonergic effects. Cariprazine can inhibit CYP2D6, reducing dextromethorphan clearance and elevating its plasma concentration, leading to enhanced serotonin activity. Clinically, patients may present with altered mental status, autonomic instability, and neuromuscular abnormalities."
"Dextromethorphan inhibits CYP2B6 and CYP2C9, which are involved in valproic acid metabolism. This results in decreased valproic acid clearance, potentially elevating valproic acid serum concentrations and increasing the risk of dose-dependent adverse effects such as hepatotoxicity, thrombocytopenia, and sedation. Concurrent use requires dose adjustment and close monitoring for signs of valproate toxicity."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about DELSYM vs DEXTROMETHORPHAN POLISTIREX, answered by our medical review team.
DELSYM is a Antitussive that works by Dextromethorphan is a non-competitive NMDA receptor antagonist and sigma-1 receptor agonist, which suppresses cough by elevating the threshold for coughing in the medullary cough center.. DEXTROMETHORPHAN POLISTIREX is a Antitussive that works by Dextromethorphan polistirex is an NMDA receptor antagonist and sigma-1 receptor agonist. It inhibits serotonin reuptake and acts on the brain stem cough center to elevate the threshold for coughing.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DELSYM and DEXTROMETHORPHAN POLISTIREX depend on the specific clinical indication. These are both Antitussive agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of DELSYM is: 60 mg orally every 12 hours (extended-release suspension).. The standard adult dose of DEXTROMETHORPHAN POLISTIREX is: 30-60 mg orally every 12 hours; not to exceed 120 mg in 24 hours.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between DELSYM and DEXTROMETHORPHAN POLISTIREX in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. DELSYM is classified as Category C. Category D (positive evidence of human fetal risk): First trimester exposure associated with rare reports of congenital malformations including cardiac defects and oral clefts base. DEXTROMETHORPHAN POLISTIREX is classified as Category C. No well-controlled studies in pregnant women. Animal studies have not shown evidence of fetal harm. Based on limited human data, risk of major congenital malformations is low. Avoi. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.