CHLORPHENIRAMINE MALEATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHLORPHENIRAMINE MALEATE (CHLORPHENIRAMINE MALEATE).
H1 receptor antagonist; competitively blocks histamine at H1 receptors, preventing histamine-mediated symptoms such as vasodilation, increased capillary permeability, and smooth muscle contraction.
| Metabolism | Hepatic via CYP450 (CYP2D6, CYP3A4); first-pass effect; major metabolites include desmethylchlorpheniramine. |
| Excretion | Renal: ~50% as metabolites; Fecal: negligible; Biliary: minor. |
| Half-life | Terminal elimination half-life: 12-15 hours (prolonged in hepatic impairment). |
| Protein binding | 72-96% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Vd: 3.0-7.0 L/kg (extensive tissue distribution). |
| Bioavailability | Oral: ~30-50% (first-pass metabolism); IM: ~100%. |
| Onset of Action | Oral: 0.5-1 hour; IM: ~30 minutes; IV: immediate. |
| Duration of Action | Oral: 4-6 hours (dose-dependent); sustained-release formulations: up to 12 hours. |
| Molecular Weight | 390.87 |
| Action Class | First-generation alkylamine antihistamine |
4 mg orally every 4-6 hours, not to exceed 24 mg per day; or 10-20 mg intramuscularly or intravenously as a single dose, not to exceed 40 mg per day.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: administer every 6 hours; GFR <10 mL/min: administer every 8 hours. |
| Liver impairment | Child-Pugh Class C: reduce dose by 50% or administer every 12 hours; Class A or B: no adjustment necessary. |
| Pediatric use | Children 2-5 years: 1 mg orally every 4-6 hours, not to exceed 6 mg per day; Children 6-11 years: 2 mg orally every 4-6 hours, not to exceed 12 mg per day; Children ≥12 years: same as adult. |
| Geriatric use | Initiate at 4 mg orally every 8-12 hours due to increased risk of anticholinergic effects and sedation; maximum daily dose 12 mg. |
| 1st trimester | Limited data; avoid unless potential benefit outweighs risk. Animal studies not always predictive. Use lowest effective dose. |
| 2nd trimester | Generally considered safe in short-term use. Caution with prolonged use or high doses due to potential anticholinergic effects. |
| 3rd trimester | Avoid near term due to risk of respiratory depression and anticholinergic effects in neonate. Use lowest effective dose if necessary. |
Clinical note
Comprehensive clinical and safety monograph for CHLORPHENIRAMINE MALEATE (CHLORPHENIRAMINE MALEATE).
| Placental transfer | Crosses placenta; achieves fetal concentrations similar to maternal plasma levels. |
| Breastfeeding | Excreted into breast milk in small amounts. Despite low levels, caution is advised due to potential anticholinergic effects and irritability in infants. Use lowest effective dose for shortest duration. |
■ FDA Black Box Warning
None
| Common Effects | Drowsiness, Sedation, Dizziness, Dry mouth, nose, and throat, Blurred vision, Urinary retention, Constipation, Gastrointestinal upset |
| Serious Effects | Respiratory depression (especially in children), Seizures, Cardiac arrhythmias (e.g., QT prolongation, torsades de pointes), Severe hypotension, Anaphylaxis, Acute dystonic reactions, Agranulocytosis (rare) |
Hypersensitivity to chlorpheniramine or any componentSevere hypertensionCoronary artery diseaseAngle-closure glaucomaUrinary retentionAsthma attack (acute)Concomitant use with MAOIs
| Precautions | May cause drowsiness and impair ability to drive or operate machinery, Use with caution in patients with asthma, COPD, or urinary retention, Avoid concomitant use with CNS depressants, Elderly patients more susceptible to anticholinergic effects |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate controlled studies in pregnant women. First trimester: no known teratogenic effects; second and third trimesters: potential for anticholinergic effects, respiratory depression, or apnea in neonates if used near term. Avoid during labor and delivery due to possible adverse effects on uterine contractility. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to potential anticholinergic effects. In late pregnancy, assess fetal heart rate and uterine activity if used near term, especially with high doses. Neonatal monitoring for signs of anticholinergic toxicity or respiratory depression post-delivery. |
| Fertility Effects | Limited data; no known significant effects on fertility in humans. Animal studies have not shown impaired fertility. Anticholinergic effects may theoretically affect cervical mucus consistency, but clinical relevance is minimal. |
| No significant food interactions. Alcohol should be avoided due to additive sedative effects. |
| Clinical Pearls | Chlorpheniramine maleate is a first-generation antihistamine with significant anticholinergic properties. Onset of action is 30-60 minutes, duration 4-6 hours. It is more sedating than newer antihistamines, which can be exploited for nighttime pruritus. Avoid in patients with narrow-angle glaucoma, urinary retention, or asthma (may thicken secretions). May cause paradoxical excitation in children. |
| Patient Advice | Avoid driving or operating heavy machinery until you know how this medication affects you, as it may cause drowsiness. · Do not consume alcohol or other central nervous system depressants while taking this medication. · Take exactly as prescribed; do not exceed recommended doses. · If you miss a dose, skip it and resume your normal schedule. Do not double dose. · Stop use and contact your doctor if you experience difficulty urinating, blurred vision, or rapid heartbeat. · Store at room temperature away from moisture and heat. |