What are some first-generation antihistamines (antihistamine), and what are their typical doses?

First-Generation Antihistamines: Options and Dosing

Second-generation antihistamines should be strongly preferred over first-generation antihistamines for allergic rhinitis due to their superior safety profile, and first-generation agents should only be used as a last resort after ensuring patients understand the risks of safer alternatives. 1, 2, 3

Why First-Generation Antihistamines Should Be Avoided

First-generation antihistamines carry significant safety concerns that make them inappropriate as first-line therapy:

• Sedation and performance impairment occur frequently and may exist without the patient's subjective awareness, creating dangerous situations 1, 2
• Motor vehicle accidents are 1.5 times more likely in drivers taking first-generation antihistamines 2, 4
• Cognitive impairment includes decreased learning and school performance in children 2
• Anticholinergic effects include dry mouth, dry eyes, constipation, urinary retention, and risk of narrow-angle glaucoma exacerbation 1, 2, 4
• Elderly patients face amplified risks including falls, fractures, subdural hematomas, and heightened sensitivity to psychomotor impairment 2, 4
• Next-day impairment persists even with bedtime dosing because effects last longer than plasma levels of the parent compound 2, 4

Common First-Generation Antihistamines with Characteristics

If a first-generation antihistamine must be used despite these risks, here are the main options:

Chlorpheniramine (Most Reasonable Choice)

• Dose: 4 mg every 4-6 hours (maximum 24 mg/24 hours in adults)
• Half-life: 12-24 hours 2
• Sedation rate: Approximately 45% 2
• This is the most reasonable first-generation option due to its relatively lower sedation profile compared to diphenhydramine and hydroxyzine while maintaining efficacy 2

Diphenhydramine (Benadryl)

• Dose: 25-50 mg every 4-6 hours (maximum 300 mg/24 hours in adults) 4, 5
• Half-life: 2.6-4.3 hours 2
• Sedation rate: 50% of patients 2
• Note: This is the standard choice only when used as adjunctive therapy in anaphylaxis (25-50 mg IV/oral), not for routine allergic rhinitis 4

Hydroxyzine

• Dose: 25-50 mg every 6-8 hours in adults
• Half-life: 20 hours 2
• Sedation rate: 80% (very high) 2
• This agent has the highest sedation rate and should be avoided for allergic rhinitis 2

Clemastine

• Dose: 1.34-2.68 mg twice daily in adults
• Half-life: 21 hours 2
• Sedation rate: 14% (lower than diphenhydramine) 2

Critical Safety Warnings

When first-generation antihistamines are used, patients must understand:

• Concomitant use with alcohol, sedatives, or other CNS-active medications dramatically increases impairment risk 4
• Bedtime dosing does not eliminate risk as next-day sedation and performance impairment still occur 2, 4
• Rapid IV administration or large doses can cause potentially life-threatening adverse effects 5
• Occupational and driving activities should be avoided or approached with extreme caution 2, 4

The Preferred Alternative: Second-Generation Antihistamines

Second-generation antihistamines are the recommended first-line treatment for allergic rhinitis because they provide similar or superior efficacy without the dangerous side effects 1, 3:

• Fexofenadine, loratadine, and desloratadine cause no sedation at recommended doses 1, 4
• Cetirizine 10 mg once daily may cause mild drowsiness (13.7% vs 6.3% placebo) but is generally well-tolerated 1, 6
• Cost difference is minimal ($0.52-2.39 more per dose than diphenhydramine at $0.37), which is outweighed by the safety benefits 7

Clinical Bottom Line

If you must prescribe a first-generation antihistamine, chlorpheniramine 4 mg every 4-6 hours is the most reasonable choice due to its lower sedation profile compared to other first-generation agents. 2 However, this should only occur after exhausting second-generation options and ensuring the patient fully understands the risks, including impaired driving, cognitive dysfunction, and anticholinergic effects. 2, 4, 3