What is the dosage and frequency of diphenhydramine (antihistamine)?

Diphenhydramine Dosing and Frequency

For adults, administer diphenhydramine 25-50 mg every 4-6 hours (maximum 6 doses per 24 hours), and for children, use 1-2 mg/kg per dose every 4-6 hours with a maximum single dose of 50 mg. 1, 2, 3

Adult Dosing

• Standard dose: 25-50 mg per dose administered orally or parenterally every 4-6 hours, with a maximum of 6 doses in 24 hours 1, 3
• For allergic reactions requiring parenteral administration, use 25-50 mg intramuscularly or intravenously 1, 2
• When used for sedation as a procedural adjunct, administer 25-50 mg intravenously 1
• For discharge therapy following allergic reactions, prescribe diphenhydramine every 6 hours for 2-3 days 1

Important Administration Considerations for Adults

• Intravenous administration must be given slowly to minimize adverse effects including hypotension and dizziness 1
• Parenteral routes provide faster onset of action (several minutes) compared to oral administration 1, 2
• Duration of effect is 4-6 hours regardless of route 1, 2

Pediatric Dosing

• Weight-based dosing: 1-2 mg/kg per dose every 4-6 hours 1, 2
• Maximum single dose: 50 mg regardless of calculated weight-based dose 1, 2
• Children 6 to under 12 years: 10 mL (25 mg) every 4-6 hours, maximum 6 doses per 24 hours 3
• Children under 6 years: FDA labeling states "do not use" for over-the-counter products 3

Pediatric Pharmacokinetic Considerations

• Children have significantly faster clearance rates (49.2 mL/min/kg) and shorter elimination half-lives (5.4 hours) compared to adults, which supports the every 4-6 hour dosing interval 4

Route-Specific Guidance

• For anaphylaxis: Parenteral administration (IM or IV) is preferred for faster onset, but diphenhydramine is always second-line to epinephrine and should never be administered alone 1, 2
• Oral administration: Appropriate for mild allergic reactions, urticaria, and maintenance therapy 3
• Intravenous administration: Reserved for acute severe reactions or procedural sedation, must be given slowly 1

Clinical Algorithm for Allergic Reactions

1. First-line: Administer epinephrine for anaphylactic reactions 2
2. Adjunctive therapy: Give diphenhydramine 25-50 mg IM (adults) or 1-2 mg/kg IM (children, max 50 mg) 2
3. Consider adding: H2-antagonist such as ranitidine, as the combination is superior to diphenhydramine alone for urticaria 2
4. Corticosteroids: Administer hydrocortisone 200 mg IV for adults to prevent biphasic reactions 2

Critical Safety Warnings

• Never replace epinephrine with diphenhydramine as first-line treatment for anaphylaxis 2
• Common adverse effects include dizziness, blurred vision, dry mouth, hypotension, urinary retention, and wheezing 1
• Hypnotic effects are significantly increased when combined with alcohol, benzodiazepines, or opioid narcotics 1
• Elderly adults have prolonged elimination half-lives (13.5 hours) and reduced clearance, increasing risk of adverse effects 4
• Recent evidence suggests diphenhydramine has a problematic therapeutic ratio with higher adverse effects in children and older adults, leading some countries to restrict access 5

Special Populations

• Elderly adults: Consider dose reduction due to significantly prolonged half-life (13.5 hours vs 9.2 hours in young adults) and reduced clearance 4
• Toxic ingestions: Children under 6 years ingesting ≥7.5 mg/kg, or patients ≥6 years ingesting ≥7.5 mg/kg or 300 mg (whichever is less) require emergency department evaluation 6