Diphenhydramine Dosing in Pediatrics

Standard Weight-Based Dosing

The recommended diphenhydramine dose is 1–2 mg/kg per dose, with a maximum single dose of 50 mg regardless of weight. 1

This dosing range applies to both oral and parenteral routes when diphenhydramine is clinically indicated 1
Doses may be repeated every 4–6 hours as needed, but each individual dose must not exceed 50 mg 1
For younger children and infants (when use is appropriate), start at the lower end of the range (1 mg/kg) 2

Liquid formulations are absorbed more rapidly than tablets, making them preferred for acute allergic reactions 1, 2
The typical oral dose remains 1–2 mg/kg per dose (maximum 50 mg) 1, 2

FDA-approved dosing for pediatric patients (excluding premature infants and neonates): 5 mg/kg/24 hours or 150 mg/m²/24 hours, divided into four doses 3
Maximum daily dosage is 300 mg 3
IV administration rate should generally not exceed 25 mg/min 3
For emergency anaphylaxis management, the guideline dose of 1–2 mg/kg per dose (maximum 50 mg) is used as adjunctive therapy 1

Diphenhydramine is second-line therapy to epinephrine and should NEVER be administered alone in anaphylaxis. 1

Epinephrine is the only first-line treatment for anaphylaxis 1
After epinephrine administration, diphenhydramine 1–2 mg/kg (maximum 50 mg) may be given parenterally 1
Combining diphenhydramine with ranitidine (1 mg/kg) is superior to diphenhydramine alone in anaphylaxis management 1

For children under 6 years of age, diphenhydramine should be avoided for routine allergic symptoms due to significant safety concerns. 4

Between 1969–2006,33 deaths in children under 6 years were attributed to diphenhydramine 4
The FDA Nonprescription Drugs and Pediatric Advisory Committees recommend against OTC cough and cold medications (including first-generation antihistamines) in children below 6 years 4
Second-generation antihistamines (cetirizine, loratadine) are preferred for routine allergy management in young children 4

Children under 6 years who ingest ≥7.5 mg/kg of diphenhydramine require emergency department referral 5
Patients 6 years and older who ingest ≥7.5 mg/kg or 300 mg (whichever is less) require emergency department evaluation 5

For a 10 kg child (approximately 1 year old):

Dose range: 10–20 mg per dose
Maximum: 20 mg (do not exceed even though 2 mg/kg = 20 mg, because this approaches the safety threshold)

For a 20 kg child (approximately 6 years old):

For a 30 kg child (approximately 10 years old):

Dose range: 30–50 mg per dose
Maximum: 50 mg per dose (weight-based calculation would be 60 mg, but absolute maximum is 50 mg)

Never use diphenhydramine as a sleep aid in children—this is explicitly contraindicated 4
Avoid OTC combination products containing multiple active ingredients in children under 6 years to prevent inadvertent overdose 4
Do not substitute diphenhydramine for epinephrine in anaphylaxis or severe allergic reactions 1
Rapid IV administration may precipitate seizures—administer slowly when using parenteral routes 2
Monitor for paradoxical excitation or agitation, especially in younger pediatric patients 1, 2

Children have significantly faster clearance (49.2 ± 22.8 mL/min/kg) compared to adults (23.3 ± 9.4 mL/min/kg), resulting in shorter elimination half-lives (5.4 ± 1.8 hours in children vs 9.2 ± 2.5 hours in young adults) 6
This faster clearance supports the mg/kg dosing approach rather than simple weight-based scaling from adult doses 7, 6
After allometric scaling for body size, no additional maturation-related changes in clearance are apparent in children ≥2 years 8, 7