BROMPHENIRAMINE MALEATE, PSEUDOEPHEDRINE HYDROCHLORIDE AND DEXTROMETHORPHAN HYDROBROMIDE
Clinical safety rating: safe
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
Brompheniramine is a first-generation antihistamine that competitively inhibits histamine at H1 receptors, reducing allergic symptoms. Pseudoephedrine is a sympathomimetic amine that directly stimulates alpha-adrenergic receptors, causing vasoconstriction and nasal decongestion. Dextromethorphan is an NMDA receptor antagonist and sigma-1 receptor agonist that suppresses the cough reflex in the medulla oblongata.
| Metabolism | Brompheniramine: extensively metabolized via hepatic CYP450 (CYP2D6, CYP3A4) to desmethylbrompheniramine and other metabolites. Pseudoephedrine: partially metabolized via N-demethylation (CYP450) to norgseudoephedrine; 43-96% excreted unchanged. Dextromethorphan: primarily metabolized via CYP2D6 to dextrorphan (active), also via CYP3A4/5 to 3-methoxymorphinan. |
| Excretion | Brompheniramine: Renal (approx. 80% as metabolites, <1% unchanged). Pseudoephedrine: Renal (70-90% unchanged, rest as metabolites). Dextromethorphan: Renal (primarily as metabolites, <1% unchanged). Biliary/fecal: Minor for all three. |
| Half-life | Brompheniramine: 12-34 hours (mean ~24 h), prolonged in hepatic impairment. Pseudoephedrine: 5-8 hours (pH-dependent urinary excretion; alkaline urine prolongs half-life). Dextromethorphan: 3-4 hours (extensive metabolizers) or 18-24 hours (poor metabolizers of CYP2D6). |
| Protein binding | Brompheniramine: 60-80% (primarily albumin, alpha-1-acid glycoprotein). Pseudoephedrine: <10% (negligible). Dextromethorphan: 50-60% (possibly to albumin). |
| Volume of Distribution | Brompheniramine: 7-10 L/kg (large, due to extensive tissue distribution). Pseudoephedrine: 2.5-3.5 L/kg (moderate, distributes into body water). Dextromethorphan: 3-5 L/kg (moderate, distributed to tissues including brain). |
| Bioavailability | Brompheniramine: ~70% (oral). Pseudoephedrine: 90-100% (oral). Dextromethorphan: ~10-30% (oral, due to extensive first-pass metabolism; in poor metabolizers, bioavailability higher). |
| Onset of Action | Oral: Brompheniramine 30-60 min; Pseudoephedrine 30-60 min; Dextromethorphan 15-30 min. |
| Duration of Action | Brompheniramine: 4-6 hours (immediate-release), 12-24 hours (extended-release). Pseudoephedrine: 4-6 hours (immediate-release), 8-12 hours (extended-release). Dextromethorphan: 4-6 hours (immediate-release); extended-release formulations: up to 12 hours. Note: Extended-release combination products have durations of 12-24 hours. |
| Molecular Weight | Brompheniramine maleate: 435.19 Da; Pseudoephedrine HCl: 201.69 Da; Dextromethorphan HBr: 370.32 Da. |
| Action Class | Sympathomimetic combination: antihistamine, decongestant, antitussive |
Adults and children ≥12 years: 1 tablet (brompheniramine maleate 4 mg, pseudoephedrine HCl 60 mg, dextromethorphan HBr 15 mg) orally every 4 hours, not to exceed 4 tablets in 24 hours, or 2 tablets (extended-release) every 12 hours, not to exceed 4 tablets in 24 hours.
| Dosage form | SYRUP |
| Renal impairment | GFR ≥30 mL/min: No adjustment. GFR 10-29 mL/min: Administer every 6 hours; monitor for CNS effects. GFR <10 mL/min: Avoid use (risk of toxicity from pseudoephedrine and dextromethorphan accumulation). |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce frequency (e.g., every 6 hours) and monitor for CNS depression. Child-Pugh C: Avoid use (dextromethorphan metabolism reduced; brompheniramine may accumulate). |
| Pediatric use | Children 6-11 years: 1/2 tablet (brompheniramine maleate 2 mg, pseudoephedrine HCl 30 mg, dextromethorphan HBr 7.5 mg) orally every 4 hours, not to exceed 4 doses in 24 hours. Children 2-5 years: Not recommended (safety and efficacy not established). Children <2 years: Contraindicated (risk of respiratory depression). |
| Geriatric use | Elderly >65 years: Initiate at lowest effective dose (e.g., 1/2 tablet) every 6-8 hours due to increased anticholinergic effects, hypotension, and CNS excitation. Maximum: 2 tablets in 24 hours. Monitor for confusion, urinary retention, and elevated blood pressure. |
| 1st trimester | Limited data; avoid use due to potential teratogenic effects from first-trimester exposure, especially with pseudoephedrine (risk of gastroschisis with vasoconstrictors) and dextromethorphan (association with neural tube defects in some studies). |
| 2nd trimester | Use with caution; pseudoephedrine may reduce uterine blood flow; dextromethorphan is generally considered low risk but lacks robust safety data. Brompheniramine is older antihistamine with anticholinergic effects. |
| 3rd trimester | Avoid in third trimester due to risk of uterine contractions from pseudoephedrine, potential neonatal withdrawal from antihistamines, and respiratory depression from dextromethorphan near term. |
Clinical note
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
| FDA category | Animal |
| Placental transfer | All three components cross the placenta. Pseudoephedrine: documented transfer, may cause fetal vasoconstriction. Dextromethorphan: detectable in cord blood. Brompheniramine: lipophilic, expected to cross. |
■ FDA Black Box Warning
None.
| Common Effects | Insomnia |
| Serious Effects | Hypertensive crisis, Cardiac arrhythmias (e.g., ventricular tachycardia, atrial fibrillation), Myocardial infarction, Stroke (hemorrhagic or ischemic), Seizures, Serotonin syndrome (especially with concurrent serotonergic drugs), Severe allergic reactions (anaphylaxis, angioedema), Acute urinary retention (especially in men with prostatic hypertrophy), Increased intraocular pressure (angle-closure glaucoma), Central nervous system depression (respiratory depression, coma) in overdose |
Hypersensitivity to any componentSevere hypertension or coronary artery disease (due to pseudoephedrine)Concurrent use of MAOIs or within 14 days (hypertensive crisis risk)Narrow-angle glaucoma (anticholinergic effect of brompheniramine)Urinary retention (brompheniramine)Severe hepatic impairment (dextromethorphan metabolism)Children <6 years (due to risk of serious adverse effects from cold medications)
| Precautions | Cardiovascular effects: hypertension, palpitations, tachycardia, arrhythmias, especially in patients with pre-existing heart disease or hyperthyroidism., CNS depression: avoid concurrent use with alcohol or other sedatives; may impair mental/physical abilities., Serotonin syndrome: risk with concomitant serotonergic drugs including MAOIs, SSRIs, SNRIs, triptans, linezolid, methylene blue., QT prolongation: caution with drugs that prolong QT interval or predisposing conditions (e.g., electrolyte abnormalities, bradycardia)., Anticholinergic effects: caution in patients with glaucoma, prostatic hypertrophy, urinary retention, or asthma., Inhibition of CYP2D6: dextromethorphan may increase levels of CYP2D6 substrates (e.g., TCAs, antipsychotics). |
Loading safety data…
| Breastfeeding | Brompheniramine may reduce milk supply and cause infant drowsiness; pseudoephedrine is excreted in milk and may cause irritability; dextromethorphan is excreted in low amounts but limited data. Caution advised; use lowest effective dose for shortest duration. |
| Lactation Rating | L3 (Moderately Safe) - limited data; potential for adverse effects in infant. |
| Teratogenic Risk | Brompheniramine: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Pseudoephedrine: Case-control studies suggest small increased risk of gastroschisis and hemifacial microsomia with first-trimester use; vasoconstriction may reduce uteroplacental blood flow in third trimester. Dextromethorphan: No human teratogenicity data; animal studies show no fetal harm at therapeutic doses. Overall, combination is not recommended in first trimester; avoid in third trimester due to pseudoephedrine effects. |
| Fetal Monitoring | Monitor maternal blood pressure and fetal heart rate pattern during use, especially in third trimester. Assess for signs of premature labor or reduced fetal movement. Consider growth ultrasound if prolonged use. |
| Fertility Effects | Brompheniramine: anticholinergic effects may impair cervical mucus quality. Pseudoephedrine: sympathomimetic may reduce uterine blood flow; theoretical impact on implantation. No clinical evidence of significant fertility impairment. Dextromethorphan: no known effects on fertility. |
| Food/Dietary | Avoid alcohol, which may potentiate CNS depression. Limit caffeine intake (coffee, tea, cola) as pseudoephedrine may increase stimulant effects. High-tyramine foods (e.g., aged cheese, cured meats, fermented products) may cause hypertensive crisis if combined with MAOIs, but this combination is contraindicated. No other significant food interactions. |
| Clinical Pearls | Do not use in children under 6 years due to risk of respiratory depression from dextromethorphan. Avoid in patients with hypertension or coronary artery disease due to pseudoephedrine. Brompheniramine has pronounced anticholinergic effects; use cautiously in elderly or those with glaucoma, urinary retention, or BPH. For severe cough, dextromethorphan efficacy is limited; consider if nonproductive cough is disruptive. Maximum duration of treatment is 7 days; prolonged use may lead to rebound congestion and dependence. |
| Patient Advice | Do not take more than 6 doses in 24 hours. Do not exceed 7 days of use without consulting a doctor. · Avoid alcohol and other CNS depressants (e.g., sedatives, tranquilizers) as they may increase drowsiness. · Do not use if you have taken a monoamine oxidase inhibitor (MAOI) within the last 14 days. · Stop use and ask a doctor if symptoms do not improve within 7 days, are accompanied by fever, or if cough persists with headache, rash, or persistent headache. · Take with a full glass of water. May cause drowsiness; avoid driving or operating heavy machinery until you know how this medication affects you. · For the decongestant effect, take the last dose of the day several hours before bedtime to minimize insomnia. · Shake suspension well before use. Use only the dosing device provided. |