Maximum Recommended Dose of Diphenhydramine
The maximum single dose of diphenhydramine is 50 mg per dose for both adults and children, with adults able to take up to 6 doses in 24 hours (maximum 300 mg/day), while children should not exceed 50 mg per single dose. 1, 2, 3
Adult Maximum Dosing
- The standard adult dose is 25-50 mg per dose, with a maximum of 6 doses in 24 hours (total daily maximum: 300 mg) 3
- Dosing intervals should be every 4-6 hours 3
- This applies to all routes of administration (oral, intravenous, intramuscular) 1
Pediatric Maximum Dosing
- Children receive weight-based dosing of 1-2 mg/kg per dose, but the absolute maximum single dose is 50 mg regardless of weight 1, 2
- For children 6 to under 12 years: maximum single dose is 25 mg (10 mL of standard syrup formulation) 3
- For children 12 years and older: can receive adult dosing of 25-50 mg per dose 3
- The 50 mg maximum single dose ceiling applies even if a child's weight-based calculation (2 mg/kg) would suggest a higher dose 2
Critical Safety Thresholds
The evidence distinguishes between therapeutic maximum dosing and toxicity thresholds:
- Moderate toxicity symptoms begin appearing above 300 mg total ingestion (approximately 0.3 g) 4
- Severe symptoms (delirium, psychosis, seizures, coma) occur at doses ≥1.0 g (1000 mg) 4
- Hospitalization is recommended for ingestions above 1.0 g 4
- The American Association of Poison Control Centers recommends emergency department evaluation for ingestions ≥7.5 mg/kg 5
Route-Specific Considerations
- Intravenous administration must be given slowly to minimize adverse effects and prevent seizures 1, 2
- Oral liquid formulations are absorbed more readily than tablets for acute allergic reactions 2
- Parenteral routes are preferred for anaphylaxis due to faster onset 1
Common Pitfalls to Avoid
- Never exceed 50 mg as a single dose in children, even if weight-based calculations suggest higher doses 2
- Do not administer more frequently than every 4 hours 3
- Avoid rapid IV push, which can precipitate seizures 2
- Remember that diphenhydramine is second-line to epinephrine in anaphylaxis and should never be used alone 1, 2
- Be aware that hypnotic effects are potentiated by alcohol, benzodiazepines, and opioids 1