FDA Approved Age-Based Safety and Dosing of Diphenhydramine Syrup
Diphenhydramine syrup is FDA approved for children 6 years and older, with specific dosing recommendations based on age: children 6-11 years should receive 10 mL (25 mg) every 4-6 hours, and children 12 years and older should receive 10-20 mL (25-50 mg) every 4-6 hours, with a maximum of 6 doses in 24 hours; it is not approved for use in children under 6 years of age. 1
Age-Based Dosing Guidelines
| Age Group | Recommended Dose | Maximum Daily Dosing |
|---|---|---|
| Adults and children 12+ years | 10-20 mL (25-50 mg) | No more than 6 doses (300 mg) in 24 hours |
| Children 6-11 years | 10 mL (25 mg) | No more than 6 doses (150 mg) in 24 hours |
| Children under 6 years | Do not use | Not approved for this age group |
Safety Considerations
Toxicity Thresholds
- For children under 6 years (though not FDA approved): ingestions of ≥7.5 mg/kg are considered potentially toxic and require emergency department evaluation 2, 3
- For patients 6 years and older: ingestions of ≥7.5 mg/kg or 300 mg (whichever is less) warrant emergency department referral 2
Common Adverse Effects
- Somnolence is the most commonly reported adverse effect (95% of pediatric subjects in pharmacokinetic studies) 4
- Other common adverse effects in children include:
- Anticholinergic effects: tachycardia (53.4%), hallucinations (46.5%), mydriasis (26.3%)
- Central nervous system effects: somnolence (34.7%), agitation (33.9%) 5
Serious Adverse Effects
- Seizures (rare, occurring in only 5.5% of pediatric cases with adverse events) 5
- QRS prolongation and cardiac conduction abnormalities (in significant overdoses)
- Respiratory depression (in severe overdoses)
Important Clinical Considerations
Formulation matters: Liquid pediatric formulations are associated with the highest frequency of accidental ingestions in children (51.7% of cases) 5
Risk of accidental ingestion: The majority (74.7%) of diphenhydramine exposures in children 2-4 years involve accidental unsupervised ingestions 5
Alternative options: Second-generation antihistamines have similar efficacy with fewer adverse effects, particularly important for children and older adults 6
Monitoring parameters: When administering diphenhydramine to children, monitor for:
- Excessive sedation
- Paradoxical excitation
- Anticholinergic effects (dry mouth, flushing, urinary retention)
- Changes in vital signs
Administration timing: Diphenhydramine should be administered every 4-6 hours as needed, not exceeding the maximum daily dose 1
When using diphenhydramine in emergency situations such as anaphylaxis, the recommended parenteral dose is 1-2 mg/kg or 25-50 mg per dose 7, but this route should be reserved for situations where oral administration is not possible or rapid onset of action is required.