Pediatric Diphenhydramine Dosing
For children 6 years and older, administer 1-2 mg/kg per dose (maximum 50 mg) every 4-6 hours, not exceeding 6 doses in 24 hours; for children under 6 years, the FDA-approved dosing is 10 mL (25 mg) for ages 6 to under 12 years, while children under 6 years should not use over-the-counter diphenhydramine without physician direction. 1
Standard Pediatric Dosing by Age and Weight
Children 6 to Under 12 Years
- Dose: 10 mL (25 mg) every 4-6 hours 1
- Alternative weight-based dosing: 1-2 mg/kg per dose, maximum 50 mg 2
- Maximum: 6 doses in 24 hours (not to exceed 300 mg daily) 3, 1
Children Under 6 Years
- FDA labeling: "Do not use" for over-the-counter administration 1
- Physician-directed dosing: 1-2 mg/kg per dose when medically indicated 2
- Toxic threshold: Ingestions ≥7.5 mg/kg warrant emergency department evaluation 4, 5
Adolescents (12 Years and Older)
Route Selection Based on Clinical Context
Oral Administration
- Liquid formulations are preferred over tablets for acute allergic reactions requiring rapid absorption 2, 3
- Onset: 20-30 minutes PO 2
- Peak effect: 45-60 minutes PO 2
- Duration: 4-6 hours 2, 3
Parenteral Administration (IM/IV)
- Use when: Patient cannot tolerate oral medications, rapid symptom control needed, or treating anaphylaxis as adjunctive therapy 2, 3
- Dose: 1-2 mg/kg per dose, maximum 50 mg 2
- Onset: 5-10 minutes IV, 15 minutes IM 2
- Peak effect: 30 minutes IV, 1 hour IM 2
Critical Clinical Context: When Diphenhydramine is NOT First-Line
Diphenhydramine should NEVER be used as monotherapy for anaphylaxis. 3
Anaphylaxis Treatment Algorithm
- First-line: Epinephrine 0.01 mg/kg IM (maximum 0.3 mg for children <25 kg, 0.5 mg for ≥25 kg) 2
- Adjunctive therapy (after epinephrine):
- Supportive measures: Recumbent positioning, oxygen, IV fluids, albuterol for bronchospasm 2
Special Clinical Situations
Chemical Restraint for Agitation (Ages 6-12 Years)
- Combination therapy: Haloperidol 0.1 mg/kg PO/IM/IV + diphenhydramine 0.1 mg/kg PO/IM/IV 2
- May repeat every 20-30 minutes as needed 2
- Purpose: Diphenhydramine reduces extrapyramidal symptoms from antipsychotics 2
Acute Urticaria
- Diphenhydramine 1-2 mg/kg every 4-6 hours 2, 3
- Consider combination with H2-antagonist for superior efficacy 2
Important Safety Considerations and Pitfalls
Toxicity Threshold
- Children <6 years: Ingestions ≥7.5 mg/kg require emergency department evaluation 4, 5
- Children ≥6 years: Ingestions ≥7.5 mg/kg OR ≥300 mg (whichever is less) require emergency department evaluation 4
- In a validation study of 305 children under 6 years, 99.7% who ingested <7.5 mg/kg had no serious clinical effects 5
Common Adverse Effects
- Sedation is the most common side effect (reported in 95% of pediatric subjects in pharmacokinetic studies) 6
- Other effects: dizziness, blurred vision, dry mouth, hypotension, urinary retention 3
- Paradoxical excitation can occur, especially in younger children 2
Contraindications to Home Management
- Refer to emergency department if: Agitation, hallucinations, seizures, abnormal muscle movements, loss of consciousness, respiratory depression, or any moderate-to-severe symptoms beyond mild drowsiness 4
- Suicidal intent, intentional abuse, or suspected malicious intent (child abuse) 4
Drug Interactions
- Enhanced sedation with alcohol, benzodiazepines, or opioid narcotics 3
- Anticholinergic effects may worsen delirium from other anticholinergic drugs 2
Pharmacokinetic Considerations
Weight-age dosing schedules achieve more consistent drug exposure across pediatric age groups than simple age-based dosing. 6
- After allometric scaling for body weight, no maturation-related changes in clearance were observed across ages 2-17 years 6
- Over an 8-fold dose range (6.25-50 mg), Cmax and AUC increased only 90-140% across age groups, with similar time to peak (1.5 hours) 6
- This supports weight-based dosing (1-2 mg/kg) as more physiologically appropriate than fixed age-based dosing 6, 7