Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
DELSYM vs GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE
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.
Guaifenesin is an expectorant that increases respiratory tract fluid secretions, reducing mucus viscosity. Dextromethorphan is a centrally acting cough suppressant that binds to NMDA receptors and sigma-1 receptors, elevating the cough threshold.
Symptomatic relief of cough caused by minor throat and bronchial irritation
Temporary relief of cough due to minor throat and bronchial irritation (FDA-approved),Off-label: symptomatic treatment of upper respiratory tract infections with cough and congestion
60 mg orally every 12 hours (extended-release suspension).
For adults and children ≥12 years: 10 m L (200 mg guaifenesin, 20 mg dextromethorphan) orally every 4 hours, not to exceed 60 m L (1200 mg guaifenesin, 120 mg dextromethorphan) per 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.
Guaifenesin: 1-2 hours; Dextromethorphan: 3-6 hours (extensive metabolizers), 18-24 hours (poor metabolizers due to CYP2D6 polymorphism).
Metabolized primarily by CYP2D6 to dextrorphan, an active metabolite; also undergoes O-demethylation and N-demethylation.
Guaifenesin is metabolized by oxidation and demethylation; dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan (active metabolite) and other metabolites.
Renal excretion of unchanged drug and metabolites, primarily dextrorphan glucuronide; <5% excreted unchanged in urine. Biliary/fecal elimination is negligible.
Guaifenesin: ~60% renal (metabolites), ~35% fecal; Dextromethorphan: ~70% renal (parent and metabolites, 45% as unchanged dextrorphan), ~20% biliary/fecal.
~45-50% bound to plasma albumin; main binding protein is albumin.
Guaifenesin: negligible (<10%); Dextromethorphan: ~60-70% (mainly albumin and alpha-1-acid glycoprotein).
5-6 L/kg, indicating extensive tissue distribution.
Guaifenesin: 1.2 L/kg (distributes into tissues); Dextromethorphan: 5-7 L/kg (large Vd due to high tissue binding).
Oral: ~10-25% due to extensive first-pass metabolism (CYP2D6 and CYP3A4); bioavailability is higher in poor metabolizers.
Oral: Guaifenesin ~95%; Dextromethorphan ~11% (extensive first-pass metabolism, variable due to CYP2D6).
No dose adjustment recommended for mild-to-moderate renal impairment; safety in severe renal impairment not established.
No specific guidelines; use with caution in severe renal impairment (Cr Cl <30 m L/min) due to potential accumulation of dextromethorphan metabolite.
No dose adjustment recommended for mild-to-moderate hepatic impairment; safety in severe hepatic impairment not established.
For dextromethorphan: Child-Pugh class C: consider reducing dose by 50% or avoid use; Child-Pugh A/B: no specific adjustment but monitor for CNS effects.
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 6-11 years: 5 m L (100 mg guaifenesin, 10 mg dextromethorphan) every 4 hours, max 30 m L/day. Children 2-5 years: 2.5 m L (50 mg guaifenesin, 5 mg dextromethorphan) every 4 hours, max 15 m L/day. Not for children <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.
Use the lowest effective dose; consider starting with 5 m L (100 mg guaifenesin, 10 mg dextromethorphan) every 4-6 hours due to increased risk of sedation and anticholinergic effects.
None
None.
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
Avoid use in patients with chronic cough (e.g., smoking, asthma, emphysema) or cough with excessive phlegm.,Concomitant use with MAOIs or within 2 weeks of MAOI use is contraindicated.,Dextromethorphan abuse potential; use caution with CYP2D6 inhibitors.
Hypersensitivity to dextromethorphan or any component,Use with or within 14 days of MAO inhibitors,Use in patients with respiratory depression or severe asthma
Hypersensitivity to guaifenesin or dextromethorphan,Concurrent use or recent use (within 2 weeks) of monoamine oxidase inhibitors (MAOIs),Severe hypertension, coronary artery disease, or narrow-angle glaucoma (due to sympathomimetic effects if combined with decongestants; note: this combination alone does not contain decongestants, but caution applies)
No significant food interactions. Avoid grapefruit juice as it may increase dextromethorphan levels. Take with or without food.
No significant food interactions; avoid alcohol as it may increase sedation and dizziness.
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.
Guaifenesin: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Dextromethorphan: No increased risk of major malformations in first trimester; animal studies show no teratogenicity. Avoid excessive doses in third trimester due to potential neonatal withdrawal or respiratory depression. Overall, both agents are considered low risk but use only if clearly needed.
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.
Guaifenesin: Excreted in breast milk in small amounts; unlikely to cause adverse effects in infants. Dextromethorphan: Excreted in breast milk; limited data suggest low infant exposure (M/P ratio not established). Both are considered compatible with breastfeeding; use lowest effective dose and monitor infant for sedation or respiratory depression.
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 pharmacokinetic data to support dose adjustments during pregnancy; use lowest effective dose for shortest duration. Guaifenesin: increased renal clearance in pregnancy may theoretically reduce efficacy, but no dose adjustment recommended. Dextromethorphan: metabolism by CYP2D6 may be affected by pregnancy; avoid exceeding standard doses.
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).
Monitor for sedation and dizziness, especially in elderly; avoid use with MAOIs due to serotonin syndrome risk; dextromethorphan has abuse potential at high doses; use caution in patients with chronic cough due to smoking, asthma, or COPD; guaifenesin may cause renal calculi with prolonged high doses.
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 exceed recommended doses; high doses can cause serious side effects including hallucinations and addiction.,Avoid driving or operating machinery if you feel dizzy or drowsy.,Do not use with other cough and cold medications to avoid overdose.,Increase fluid intake to help loosen mucus.,Stop use and consult a doctor if cough persists more than 7 days or comes with fever, rash, or headache.,Inform your doctor about all medications you take, especially MAOIs or SSRIs.,Keep out of reach of children; accidental overdose may be fatal in children.
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 GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE, 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.. GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is a Expectorant/Antitussive Combination that works by Guaifenesin is an expectorant that increases respiratory tract fluid secretions, reducing mucus viscosity. Dextromethorphan is a centrally acting cough suppressant that binds to NMDA receptors and sigma-1 receptors, elevating the cough threshold.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between DELSYM and GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE depend on the specific clinical indication. These are agents from distinct pharmacological classes 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 GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is: For adults and children ≥12 years: 10 m L (200 mg guaifenesin, 20 mg dextromethorphan) orally every 4 hours, not to exceed 60 m L (1200 mg guaifenesin, 120 mg dextromethorphan) per 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 GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE 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. GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is classified as Category C. Guaifenesin: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Dextromethorphan: No increased risk of major malformations in first trimester; . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.