GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE (GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE).
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.
| Metabolism | Guaifenesin is metabolized by oxidation and demethylation; dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan (active metabolite) and other metabolites. |
| Excretion | Guaifenesin: ~60% renal (metabolites), ~35% fecal; Dextromethorphan: ~70% renal (parent and metabolites, 45% as unchanged dextrorphan), ~20% biliary/fecal. |
| Half-life | Guaifenesin: 1-2 hours; Dextromethorphan: 3-6 hours (extensive metabolizers), 18-24 hours (poor metabolizers due to CYP2D6 polymorphism). |
| Protein binding | Guaifenesin: negligible (<10%); Dextromethorphan: ~60-70% (mainly albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Guaifenesin: 1.2 L/kg (distributes into tissues); Dextromethorphan: 5-7 L/kg (large Vd due to high tissue binding). |
| Bioavailability | Oral: Guaifenesin ~95%; Dextromethorphan ~11% (extensive first-pass metabolism, variable due to CYP2D6). |
| Onset of Action | Oral: Guaifenesin ~30 minutes; Dextromethorphan: 15-30 minutes. |
| Duration of Action | Oral: Guaifenesin 4-6 hours; Dextromethorphan: 4-6 hours (extensive metabolizers), up to 12 hours (poor metabolizers). |
For adults and children ≥12 years: 10 mL (200 mg guaifenesin, 20 mg dextromethorphan) orally every 4 hours, not to exceed 60 mL (1200 mg guaifenesin, 120 mg dextromethorphan) per 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of dextromethorphan metabolite. |
| Liver impairment | 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. |
| Pediatric use | Children 6-11 years: 5 mL (100 mg guaifenesin, 10 mg dextromethorphan) every 4 hours, max 30 mL/day. Children 2-5 years: 2.5 mL (50 mg guaifenesin, 5 mg dextromethorphan) every 4 hours, max 15 mL/day. Not for children <2 years. |
| Geriatric use | Use the lowest effective dose; consider starting with 5 mL (100 mg guaifenesin, 10 mg dextromethorphan) every 4-6 hours due to increased risk of sedation and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE (GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE).
| Breastfeeding | 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. |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["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)"]
| Precautions | ["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."] |
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| Fetal Monitoring | Routine prenatal care; no specific monitoring required for these agents. Monitor for respiratory depression if dextromethorphan used in high doses or with other CNS depressants. In neonates, observe for withdrawal symptoms if chronic high-dose maternal use (unlikely with combination). |
| Fertility Effects | No adverse effects on fertility reported for guaifenesin or dextromethorphan at therapeutic doses. Animal studies show no impairment of fertility. |