Are long-term antihistamines harmful?

Long-Term Antihistamine Safety Concerns

Second-generation antihistamines are generally safe for long-term use, while first-generation antihistamines should be avoided for chronic therapy due to significant risks of sedation, performance impairment, and anticholinergic effects. 1

First vs. Second Generation Antihistamines: Safety Profiles

First-Generation Antihistamines (Avoid for Long-Term Use)

• Associated with significant adverse effects:
  • Sedation and drowsiness
  • Cognitive and performance impairment (even without subjective awareness)
  • Anticholinergic effects (dry mouth, constipation, urinary retention)
  • Increased risk of falls and accidents, especially in older adults
  • Impaired learning and school performance in children
  • 1.5× higher risk of fatal automobile accidents 1

• These medications cross the blood-brain barrier readily due to their lipophilic properties 2
• Performance impairment can persist into the next day even when taken at bedtime 1

Second-Generation Antihistamines (Preferred for Long-Term Use)

• Much better safety profile for chronic use:
  • Minimal or no sedation at recommended doses (varies by agent)
  • Minimal anticholinergic effects
  • Less impairment of cognitive function and performance
  • Longer duration of action allowing for once or twice daily dosing 1

Safety Differences Among Second-Generation Antihistamines

Not all second-generation antihistamines are equal in their safety profiles:

1. Non-sedating even at higher doses:

   • Fexofenadine (safest option) 1, 3

2. Non-sedating at recommended doses but may cause sedation at higher doses:

   • Loratadine
   • Desloratadine 1

3. May cause sedation even at recommended doses:

   • Cetirizine (sedation in approximately 10% of patients)
   • Intranasal azelastine 1, 3

4. Historical cardiac concerns (no longer widely available):

   • Terfenadine and astemizole (withdrawn due to QT prolongation risks) 2

Special Populations and Considerations

Older Adults

• First-generation antihistamines pose significant risks:
  • Increased sensitivity to psychomotor impairment
  • Higher fall risk and potential for subdural hematomas
  • Greater susceptibility to anticholinergic effects
  • May worsen cognitive impairment 1

Pregnancy

• Best to avoid all antihistamines if possible, especially during first trimester
• If necessary:
  • Loratadine and cetirizine are FDA Pregnancy Category B (no evidence of harm but limited human data)
  • Hydroxyzine is specifically contraindicated in early pregnancy 1

Renal Impairment

• Acrivastine: Avoid in moderate renal impairment
• Cetirizine/levocetirizine: Reduce dose by half
• Loratadine/desloratadine: Use with caution in severe renal impairment 1

Hepatic Impairment

• Several antihistamines require caution or are contraindicated in liver disease
• Chlorphenamine and hydroxyzine should be avoided in severe liver disease 1

Practical Recommendations for Long-Term Use

1. First choice: Second-generation antihistamines, particularly fexofenadine for best balance of efficacy and safety 3

2. Avoid: First-generation antihistamines for chronic use due to safety concerns 1

3. Dosing considerations:

   • Regular scheduled dosing is more effective than as-needed use for chronic conditions 4
   • Avoid AM/PM combination regimens (second-generation in morning, first-generation at night) as the sedative effects can persist into the next day 1

4. Monitoring:

   • Be alert for subtle signs of impairment even with second-generation agents
   • Consider periodic medication holidays to reassess need for continued therapy

Potential Pitfalls in Long-Term Antihistamine Use

• Reliance on antihistamines could delay use of more effective treatments for severe allergic reactions 1
• Patient may develop tolerance to antihistamine effects over time, requiring dose adjustments
• Patients may not report sedation despite experiencing performance impairment 1
• Combination with other CNS depressants (alcohol, sedatives) can enhance impairment 1

By following these evidence-based recommendations and selecting the appropriate antihistamine, long-term therapy can be both safe and effective for managing chronic allergic conditions.