What is the recommended approach for screening antihistaminic (anti-histamine) drugs?

Screening Approach for Antihistaminic Drugs

When screening antihistaminic drugs, second-generation antihistamines should be prioritized over first-generation agents due to their superior safety profile, particularly for older adults, patients with renal or hepatic impairment, and children. 1, 2

Patient-Specific Considerations

• Age-related factors:

  • For older adults, second-generation antihistamines (fexofenadine, loratadine, desloratadine) are strongly preferred due to less sedation and fewer anticholinergic effects 1
  • No currently licensed antihistamines are contraindicated in children 12 years and older, but dosing and age restrictions vary for younger children 3
  • First-generation antihistamines may impair learning ability in children due to sedative effects 4

• Renal impairment:

  • Acrivastine should be avoided in moderate renal impairment (creatinine clearance 10-20 mL/min) 3
  • Cetirizine, levocetirizine, and hydroxyzine doses should be halved in moderate renal impairment 3, 1
  • Cetirizine, levocetirizine, and alimemazine should be avoided in severe renal impairment (creatinine clearance <10 mL/min) 3
  • Loratadine and desloratadine should be used with caution in severe renal impairment 3

• Hepatic impairment:

  • Mizolastine is contraindicated in significant hepatic impairment 3
  • Alimemazine should be avoided due to hepatotoxicity risk 3
  • Chlorphenamine and hydroxyzine should be avoided in severe liver disease due to inappropriate sedating effects 3, 1

• Pregnancy considerations:

  • Best to avoid all antihistamines in pregnancy, especially during first trimester 3
  • Hydroxyzine is specifically contraindicated during early pregnancy 3, 5
  • Chlorphenamine is often chosen when antihistamine therapy is necessary due to long safety record 3
  • Loratadine and cetirizine are FDA Pregnancy Category B drugs 3

Efficacy and Safety Screening

• First-generation antihistamines:

  • Effective for treating hyperhistaminic conditions but frequently induce sedation (>50% of patients) 4
  • May be appropriate for nighttime use when sedation is beneficial for sleep 5
  • Doxepin has useful antihistaminic properties but has sedating and anticholinergic side effects 3

• Second-generation antihistamines:

  • Loratadine, desloratadine, cetirizine, and fexofenadine are preferred for daytime use 2, 6
  • Fexofenadine may offer best overall balance of effectiveness and safety 6
  • Cetirizine is the most potent antihistamine but may cause noticeable sedation in about 10% of patients 6

• Third-generation antihistamines:

  • Loratadine, fexofenadine, mizolastine, ebastine, azelastine, and cetirizine have few adverse events 4
  • No clinically relevant cytochrome P450-mediated drug interactions or QT interval prolongation 4

Screening for Potential Adverse Reactions

• Sedation risk:

  • First-generation antihistamines have high sedation potential that can persist longer than plasma levels 1, 2
  • Second-generation antihistamines have minimal sedation at recommended doses 2
  • Performance impairment can occur without subjective awareness of drowsiness 1

• Cardiac effects:

  • Avoid terfenadine and astemizole due to risk of QT prolongation and torsades de pointes 4
  • Third-generation antihistamines do not cause clinically relevant QT interval prolongation 4

• Anticholinergic effects:

  • First-generation antihistamines have significant anticholinergic effects (dry mouth, dry eyes, constipation, urinary retention) 1
  • These effects are particularly problematic in older adults and those with narrow-angle glaucoma 1

Screening Algorithm for Antihistamine Selection

1. Determine if antihistamine is truly necessary for the patient's condition 1
2. Screen for patient-specific risk factors (age, renal/hepatic function, pregnancy status) 3, 1
3. For daytime use, select a second-generation antihistamine (fexofenadine, loratadine, desloratadine) 2, 6
4. For nighttime use when sedation is beneficial, consider first-generation antihistamines 5
5. For patients with renal or hepatic impairment, adjust selection based on specific contraindications 3, 1
6. Monitor for adverse effects including sedation, falls, confusion, dry mouth, constipation, and urinary retention 1

Special Considerations for Allergic Testing

• Antihistamines with anti-histamine activity must be discontinued a few days before skin testing 3
• Pre-treatment with antihistamines will not reduce the severity of anaphylaxis 3
• There is no evidence supporting the use of H2-blocking drugs in immediate management of anaphylaxis 3