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). |
| Molecular Weight | Guaifenesin: 198.22 Da; Dextromethorphan HBr: 370.33 Da |
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 | Limited human data; guaifenesin has been associated with increased risk of neural tube defects in some animal studies, though human data insufficient; dextromethorphan generally avoided due to lack of safety data. Use only if benefit outweighs risk. |
| 2nd trimester | No well-controlled studies; guaifenesin and dextromethorphan are generally avoided unless clearly needed. Consider non-pharmacologic alternatives. |
| 3rd trimester | Potential risk of dextromethorphan causing neonatal respiratory depression if used near term; guaifenesin may affect uterine contractility. Avoid in third trimester unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE (GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE).
| Placental transfer | Both guaifenesin and dextromethorphan are expected to cross the placenta due to their molecular weights (low to moderate) and lipophilicity. Dextromethorphan and its active metabolite have been shown to cross the placenta in animal models. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to guaifenesin, dextromethorphan, or any componentConcurrent use or within 14 days of MAO inhibitors (due to risk of serotonin syndrome)Selective serotonin reuptake inhibitors (SSRIs) use with dextromethorphan increases serotonin syndrome riskAsthma (dextromethorphan may suppress cough reflex)Chronic obstructive pulmonary disease (COPD) with productive coughInfants under 4 years of age (due to risk of respiratory depression)
| 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. |
| Food/Dietary | No significant food interactions; avoid alcohol as it may increase sedation and dizziness. |
Loading safety data…
| Excretion into breast milk is likely minimal for both components; guaifenesin has low oral bioavailability and dextromethorphan has low milk/plasma ratio. However, limited data; observe infant for sedation or feeding difficulties. Generally considered compatible with short-term use. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |