CHLOR-TRIMETON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHLOR-TRIMETON (CHLOR-TRIMETON).
Chlorpheniramine is a first-generation alkylamine antihistamine that competitively antagonizes histamine at H1 receptor sites, thereby preventing histamine-mediated symptoms such as vasodilation, increased capillary permeability, bronchoconstriction, and sensory nerve stimulation.
| Metabolism | Primarily hepatic via CYP450 isoenzymes including CYP2D6 and CYP1A2; forms active metabolites; undergoes first-pass metabolism. |
| Excretion | Primarily hepatic metabolism (N-dealkylation and oxidative pathways); renal excretion of metabolites accounts for ~70% of elimination, with <1% excreted unchanged in urine. Fecal elimination is negligible (<5%). |
| Half-life | Terminal elimination half-life is 12-15 hours in adults, with clinical context: the antihistamine effect persists longer than plasma levels due to active metabolite production and tissue binding. |
| Protein binding | Approximately 72% bound to serum albumin. |
| Volume of Distribution | Approximately 3-5 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral: 30-50% due to first-pass hepatic metabolism; Intramuscular: nearly 100%. |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 15-30 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 4-6 hours for antihistamine effect, up to 24 hours for suppression of wheal-and-flare reactions. Extended-release forms provide up to 12 hours of symptom relief. |
| Molecular Weight | 390.87 |
4 mg orally every 4-6 hours, not exceeding 24 mg/day. Also available as 8 mg or 12 mg extended-release tablets once daily at bedtime.
| Dosage form | TABLET |
| Renal impairment | GFR < 50 mL/min: reduce dose to 4 mg every 8-12 hours or 8 mg extended-release every 24 hours. GFR < 10 mL/min: use with caution, consider 4 mg every 12-24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: use with extreme caution; consider alternative therapy. |
| Pediatric use | Children 6-12 years: 2 mg orally every 4-6 hours, not exceeding 12 mg/day. Children 2-6 years: 1 mg orally every 4-6 hours, not exceeding 6 mg/day. Use weight-based: 0.1 mg/kg/dose every 6 hours, max 0.5 mg/kg/day. |
| Geriatric use | Elderly patients (≥65 years): initiate at 4 mg once daily at bedtime. May increase to 4 mg twice daily if needed. Avoid extended-release formulations; use immediate-release due to increased sensitivity and risk of anticholinergic effects. |
| 1st trimester | Avoid due to potential teratogenic effects; limited human data, but animal studies suggest risk. |
| 2nd trimester | Use only if clearly needed; may cause uterine contractions and premature labor. |
| 3rd trimester | Avoid near term; risk of severe adverse effects in neonate including respiratory depression, seizures, and feeding difficulties. |
Clinical note
Comprehensive clinical and safety monograph for CHLOR-TRIMETON (CHLOR-TRIMETON).
| Placental transfer | Chlorpheniramine crosses the placenta; limited data suggest fetal concentrations may be similar to maternal. |
| Breastfeeding | Chlorpheniramine is excreted into breast milk in small amounts; however, due to its anticholinergic effects and potential for sedation in the infant, caution is advised. Consider alternatives with lower risk, especially in neonates or preterm infants. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to chlorpheniramine or any component of the formulationNeonates and premature infantsBreastfeeding in mothers of infants <2 months of age
| Precautions | Anticholinergic effects: caution in patients with glaucoma, prostatic hyperplasia, urinary retention, or gastrointestinal obstruction, Sedation and CNS depression: avoid concurrent alcohol or other CNS depressants; caution in activities requiring alertness, Respiratory depression: avoid in lower respiratory tract symptoms (e.g., pneumonia, COPD exacerbation), Cardiovascular effects: QT prolongation at high doses; caution in preexisting cardiac disease, Elderly and debilitated patients: increased sensitivity to anticholinergic and sedative effects, Children: may cause paradoxical hyperexcitability; risk of overdose in young children |
| Food/Dietary | Avoid alcohol and grapefruit juice. Grapefruit juice may increase serum levels of chlorpheniramine. Food does not significantly affect absorption, but taking with food may reduce GI upset. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: No evidence of increased risk of major congenital anomalies based on human data; animal studies do not indicate fetal harm. Second and third trimesters: Anticholinergic effects may cause neonatal respiratory depression, irritability, and tremors if used near term. Avoid high doses in third trimester due to risk of premature contractions. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate, especially in preeclampsia or cardiac disease. Assess fetal heart rate if used near term. Neonatal observation for anticholinergic effects (e.g., constipation, urinary retention) if used in third trimester. |
| Fertility Effects | No significant adverse effects on human fertility reported. Animal studies show no impairment of fertility. Anticholinergic effects may theoretically alter cervical mucus or impair sexual function, but clinical significance is negligible. |
| Clinical Pearls | Chlor-Trimeton (chlorpheniramine) is a first-generation antihistamine with strong anticholinergic effects; use with caution in elderly due to increased risk of falls, confusion, and urinary retention. It may cause paradoxical excitation in children. Has antiemetic properties, useful for motion sickness. Avoid in patients with narrow-angle glaucoma, BPH, or severe liver disease. |
| Patient Advice | Do not drive or operate heavy machinery until you know how this medication affects you, as it may cause drowsiness. · Avoid alcohol and other CNS depressants, as they can increase drowsiness. · Take with food or milk if stomach upset occurs. · Do not crush or chew extended-release tablets; swallow whole. · Consult a doctor before use if you have asthma, glaucoma, difficulty urinating, or are pregnant or breastfeeding. · Do not use for more than 7 days for allergies or 2 days for cold symptoms, unless directed by a doctor. · Store at room temperature away from moisture and heat. · If a dose is missed, take it as soon as remembered, but skip if it's almost time for the next dose; do not double. |