Why is diphenhydramine (Benadryl) not recommended for children?

Why Diphenhydramine (Benadryl) Is Not Recommended for Children

Diphenhydramine should not be used in children under 6 years of age because it has no proven efficacy for cough or cold symptoms and carries significant risks of toxicity, including death. 1, 2

FDA and Guideline Restrictions

• The FDA drug label explicitly states "Do not use" for children under 6 years of age 2
• The American Academy of Pediatrics and FDA recommend against OTC cold medications in children under 4 years due to potential toxicity and lack of proven efficacy 1
• FDA advisory committees recommended in 2007 that OTC cough and cold medications should not be used in children below 6 years 1, 3
• Between 1969-2006, there were 69 fatalities associated with antihistamines (including diphenhydramine) in children under 6 years 1

Lack of Efficacy

• Diphenhydramine was no different than placebo in reducing nocturnal cough or sleep disturbance in both children and parents in randomized controlled trials 4
• Systematic reviews show antihistamines are no more likely than placebo to reduce acute cough in children 4
• In contrast to adults, the efficacy of antihistamines in relieving cough in children is minimal, if any 4
• Neither antihistamine monotherapy nor combinations with decongestants were effective in children ≤15 years of age 4

Safety Concerns and Toxicity Profile

• Accidental unsupervised ingestions account for 74.7% of diphenhydramine-only cases in children, with the majority (79.5%) occurring in children 2 to <4 years of age 5
• Common adverse events include tachycardia (53.4%), hallucinations (46.5%), somnolence (34.7%), agitation (33.9%), and mydriasis (26.3%) 5
• Diphenhydramine appears to be associated with a high frequency of severe adverse effects and toxicity compared to other cough and cold medications 6
• Medication errors from incorrect dosing are common, particularly in young children, and can lead to unintentional overdose 1

Specific Dosing Thresholds for Toxicity

• Children less than 6 years of age who ingest at least 7.5 mg/kg of diphenhydramine should be referred to an emergency department 7
• Patients 6 years and older who ingest at least 7.5 mg/kg or 300 mg (whichever is less) should be referred to an emergency department 7
• The narrow therapeutic window in young children makes even therapeutic errors potentially dangerous 1

Critical Pitfalls to Avoid

• Never use diphenhydramine "to make a child sleepy" - this is explicitly contraindicated on the FDA label 2
• Do not assume that because a product is available OTC, it is safe for young children 1
• Avoid using multiple products containing diphenhydramine, as this is a common cause of adverse events 1
• Liquid pediatric formulations (51.7% of cases) and solid pediatric formulations (24.0%) are most commonly involved in adverse events, so child-resistant packaging alone is insufficient protection 5

Safer Alternatives for Children

• For children over 1 year of age with acute cough, honey offers more relief than diphenhydramine or placebo 1, 8
• Vapor rub, zinc sulfate, and buckwheat honey improve symptoms in children 8
• Hypertonic saline solution can increase cough clearance without drug interactions 3

Limited Exception: Anaphylaxis Only

• Diphenhydramine at 1-2 mg/kg (25-50 mg/dose) parenterally is appropriate only as second-line therapy to epinephrine in anaphylaxis, never as monotherapy 4
• In anaphylaxis management, diphenhydramine combined with ranitidine is superior to diphenhydramine alone, but both are second-line to epinephrine 4