What are the safety considerations for using chlorpheniramine (antihistamine)?

Safety Considerations for Chlorpheniramine

Chlorpheniramine should be avoided in patients with severe liver disease due to its sedating effects and potential to precipitate hepatic encephalopathy. 1

General Safety Profile

Chlorpheniramine is a first-generation H1 antihistamine with several important safety considerations:

• Sedation and Performance Impairment:

  • Causes significant daytime drowsiness and decreased alertness even when dosed only at bedtime 1
  • Effects can persist into the next day due to prolonged plasma half-life (approximately 20 hours in adults) 2
  • Impairs cognitive function, driving ability, and increases risk of occupational accidents 1

• Anticholinergic Effects:

  • Causes dryness of mouth and eyes, constipation, urinary retention 1
  • Increases risk of narrow-angle glaucoma exacerbation 1
  • Particularly problematic in elderly patients 1

Special Populations

Liver Disease

• Contraindicated in severe liver disease due to sedating effects that may precipitate hepatic encephalopathy 1
• Second-generation antihistamines are preferred with dose adjustments in liver disease 3

Renal Impairment

• Half-life is increased in renal dysfunction 2
• Dose adjustments may be necessary in moderate to severe renal impairment

Elderly Patients

• Increased sensitivity to psychomotor impairment 1
• Higher risk for falls, fractures, and subdural hematomas 1
• More susceptible to anticholinergic adverse effects 1
• Use with extreme caution in this population, especially with comorbidities like increased intraocular pressure, benign prostatic hypertrophy, or cognitive impairment 1

Pregnancy

• Generally best to avoid all antihistamines in pregnancy, especially during first trimester 1
• However, chlorpheniramine is often chosen by clinicians in the UK when antihistamine therapy is necessary during pregnancy due to its long safety record 1
• No evidence of teratogenicity in humans, but well-controlled studies are lacking 1

Children

• Not contraindicated in children 12 years and older 1
• Half-life is decreased in children compared to adults 2
• Efficacy not established for cold and cough symptoms in children under 6 years 1
• Associated with significant safety concerns in young children, including fatalities from overdose 1

Overdose Risks

• Overdose can lead to severe central nervous system symptoms 4
• Rhabdomyolysis has been reported in severe overdose cases 4
• Acute kidney injury may occur as a complication of severe overdose 4

Practical Recommendations

1. Consider alternatives: Second-generation antihistamines (cetirizine, loratadine, fexofenadine) are generally preferred due to less sedation and fewer anticholinergic effects 1

2. Avoid AM/PM dosing regimens: Combining a second-generation antihistamine in the morning with chlorpheniramine at night is not recommended due to persistent daytime sedation 1

3. Monitor for side effects: Particularly sedation, anticholinergic effects, and performance impairment

4. Avoid in high-risk occupations: Not suitable for those who need to maintain alertness (drivers, machine operators)

5. Use lowest effective dose: Particularly important in elderly patients and those with renal or hepatic impairment

By understanding these safety considerations, clinicians can make informed decisions about the appropriate use of chlorpheniramine while minimizing risks to patients.