First-Generation Antihistamines: Common Examples
The most commonly used first-generation antihistamines include diphenhydramine, chlorpheniramine, hydroxyzine, brompheniramine, clemastine, cyproheptadine, and promethazine. 1, 2
Specific Agents and Their Characteristics
Most Frequently Used Agents
Diphenhydramine (Benadryl): Available as 25 mg and 50 mg tablets, dosed at 25-50 mg four times daily in adults, with a half-life of 2.6-4.3 hours and a 50% sedation rate 1, 2
Chlorpheniramine (Chlor-Trimeton): Available in 4 mg, 8 mg, and 12 mg formulations, dosed at 4 mg four times daily, with a half-life of 12-24 hours and approximately 45% sedation rate 1, 2
Hydroxyzine (Atarax): Available in 10 mg, 25 mg, 50 mg, and 100 mg tablets, dosed at 25 mg four times daily, with a half-life of approximately 20 hours and an 80% sedation rate 1, 2
Additional First-Generation Options
Brompheniramine (Dimetapp): Available as 12 mg tablets and 1 mg/5 mL liquid, dosed 1-2 times twice daily, with a half-life of 24.9 hours 1, 2
Clemastine (Tavist): Available in 1.34 mg and 2.68 mg tablets, dosed twice to three times daily, with a half-life of 21.3 hours and a 14% sedation rate 1, 2
Cyproheptadine (Periactin): Available as 4 mg tablets and 2 mg/5 mL liquid, dosed at 4 mg three times daily, with a half-life of 16 hours 1, 2
Promethazine (Phenergan): Listed among first-generation agents with significant sedative and anticholinergic properties 1
Critical Safety Warnings
These medications carry substantial risks that cannot be mitigated by bedtime-only dosing due to prolonged half-lives and persistent metabolites. 1, 2
Performance and Cognitive Impairment
Drivers taking first-generation antihistamines are 1.5 times more likely to be responsible for fatal automobile accidents compared to non-users 1, 2
Performance impairment occurs even without subjective awareness of drowsiness, affecting work productivity and increasing occupational accidents 1, 2
Impaired learning and decreased school performance occur in children taking these medications 1, 2
Anticholinergic Effects
Dry mouth and eyes, constipation, urinary retention, and increased risk of narrow-angle glaucoma occur with all first-generation agents 1, 2
Older adults are at particularly high risk for cognitive impairment, falls, fractures, and subdural hematomas due to pre-existing conditions like prostatic hypertrophy and elevated intraocular pressure 1, 2
Drug Interactions
- Concomitant use with alcohol, sedatives, hypnotics, or antidepressants significantly enhances performance impairment 1, 2
When First-Generation Agents May Be Considered
Before prescribing any first-generation antihistamine, physicians must ensure patients understand both the potential for adverse effects and the availability of safer second-generation alternatives. 1, 2