What is the recommended dose of Clopheniramin (Chlorpheniramine) for adults and children?

Chlorpheniramine Dosing Recommendations

For adults, chlorpheniramine should be dosed at 4 mg every 4-6 hours orally, not exceeding 24 mg daily (6 tablets), while children 6-12 years should receive 2 mg every 4-6 hours, not exceeding 12 mg daily, and the drug is not recommended for children under 6 years of age. 1

Adult Dosing

• Standard oral dose: 4 mg every 4-6 hours, maximum 24 mg per day (6 tablets in 24 hours) 1
• For nocturnal sedation as adjunct therapy in urticaria: 4-12 mg at bedtime when combined with a non-sedating daytime antihistamine 2, 3
• The higher end of the dosing range (up to 12 mg at night) may be used when sedation is desired to improve sleep in patients with urticaria, though this provides minimal additional antihistaminic effect if H1 receptors are already saturated 2

Pediatric Dosing

Children 6 to Under 12 Years

• Oral dose: 2 mg (half tablet) every 4-6 hours, maximum 12 mg daily (3 tablets in 24 hours) 1

Children Under 6 Years

• Do not use 1
• This contraindication is based on safety concerns and lack of robust efficacy data in this age group 4

Infants Under 6 Months (Emergency/Anaphylaxis Only)

• For anaphylaxis adjunctive therapy only: 250 µg/kg 3
• This should only be used in emergency situations under specialist supervision

Children 6 Months to 6 Years (Emergency/Anaphylaxis Only)

• For anaphylaxis adjunctive therapy only: 2.5 mg 3
• Again, restricted to emergency use only

Children Over 12 Years

• For anaphylaxis adjunctive therapy: 10 mg 3
• For routine allergic conditions: follow adult dosing 1

Special Populations and Dose Adjustments

Renal Impairment

• Dose reduction is required in moderate to severe renal impairment 3
• Chlorpheniramine clearance ranges from 234-470 mL/hr/kg in children, with significant renal excretion (approximately 44% of drug and metabolites recovered in urine over 48 hours) 5, 6
• Consider reducing dose by 50% in moderate renal impairment, similar to recommendations for other first-generation antihistamines 2

Hepatic Impairment

• Avoid in severe liver disease 2, 3
• The sedating effect is inappropriate and may precipitate hepatic coma in severe liver disease 2
• Chlorpheniramine undergoes extensive hepatic first-pass metabolism (bioavailability only 25-59%), making hepatic dysfunction particularly problematic 7

Elderly Patients

• Use with extreme caution; consider dose reduction 2
• Anticholinergic side effects are especially problematic in elderly patients 3
• Start with lower doses and monitor closely for sedation and anticholinergic effects

Route-Specific Considerations

Oral Administration

• Absorption lag time averages 0.7 hours (range 0.4-1.3 hours) 7
• Peak plasma levels occur at mean 2.8 hours (range 2-4 hours) after oral dosing 7
• Should be taken at least 2 hours after meals for optimal absorption 8

Intravenous Administration (Not Standard)

• IV dosing of 0.1 mg/kg has been studied in children but is not routinely recommended 5
• This route is reserved for emergency situations under specialist care

Important Clinical Considerations

Pharmacokinetic Properties

• Elimination half-life: approximately 13-28 hours in adults, shorter (9.6-13.1 hours) in children 7, 5, 6
• The longer half-life in adults suggests potential for significant accumulation with frequent dosing 7
• Children demonstrate higher clearance rates (7.23 ± 3.16 mL/min/kg) compared to adults, explaining the shorter half-life 6
• Volume of distribution is large (7.0 ± 2.8 L/kg in children), indicating extensive tissue distribution 6

Accumulation Risk

• With every 4-6 hour dosing, accumulation ratios of 4.1 to 9.4 (mean 6.5) can occur 7
• This is particularly relevant for patients on chronic therapy and supports the need for maximum daily dose limits 7

Critical Contraindications

• Absolute contraindications: severe hepatic disease, glaucoma (angle-closure), prostatic hypertrophy with urinary retention, children under 6 years for routine use 2, 3, 1
• Relative contraindications: first trimester pregnancy (though has long safety record), lactation, moderate renal impairment 2, 3

Pregnancy and Lactation

• Avoid during first trimester and throughout pregnancy when possible 2, 3
• Chlorpheniramine is often chosen when antihistamine therapy is necessary in pregnancy due to its long safety record, despite lack of controlled human studies 2
• Exercise caution during lactation 3

Drug Interactions

• Avoid concomitant use with MAO inhibitors 3
• Avoid combining with other anticholinergic medications due to additive effects 3
• Sedation is enhanced when combined with other CNS depressants 2

Common Pitfalls to Avoid

1. Overdosing in children: The pediatric dose is weight/age-based and significantly lower than adults; never use adult doses in children 1, 8

2. Ignoring renal function: Failure to adjust dose in renal impairment can lead to drug accumulation and toxicity, as 44% of drug and metabolites are renally excreted 6

3. Prescribing in severe liver disease: This can precipitate hepatic coma due to inappropriate sedation 2

4. Frequent dosing without considering accumulation: The long half-life (13-28 hours) means steady-state is not reached for 3-5 days, and accumulation is significant 7

5. Using in elderly without dose adjustment: Anticholinergic burden is particularly problematic in this population 2, 3

6. Combining with other sedating medications: This increases risk of respiratory depression and excessive sedation 2