Diphenhydramine Use in Pediatrics: Safety Concerns and Contraindications
Diphenhydramine is contraindicated in children under 6 years of age and should be used with caution in older pediatric patients due to safety concerns including potential toxicity and mortality risks. 1
Age-Based Recommendations
The FDA-approved labeling for diphenhydramine clearly states:
- Children under 6 years: Do not use 1
- Children 6 to under 12 years: 10 mL (25 mg) per dose 1
- Children 12 years and older: 10-20 mL (25-50 mg) per dose 1
Safety Concerns in Pediatric Populations
Mortality and Serious Adverse Events
The safety profile of diphenhydramine in children is concerning. Between 1969 and 2006, there were 69 fatalities associated with antihistamines in children, with diphenhydramine accounting for 33 of these deaths 2. Most deaths occurred in children under 2 years of age. These adverse events typically resulted from:
- Overdose errors
- Use of multiple cold/cough products containing antihistamines
- Medication errors
- Accidental exposures
- Intentional overdose 2
Toxicity Profile
Diphenhydramine toxicity in children can manifest as:
- Anticholinergic effects: tachycardia (53.4%), hallucinations (46.5%), mydriasis (26.3%) 3
- CNS effects: somnolence (34.7%), agitation (33.9%), seizures (5.5%) 3
- Potential for respiratory depression in severe cases 4
Specific Clinical Scenarios
Allergic Reactions and Anaphylaxis
While diphenhydramine is mentioned in anaphylaxis management guidelines, it is considered second-line therapy to epinephrine and should never be administered alone in anaphylaxis treatment 2. The recommended dosage in this emergency setting is 1-2 mg/kg or 25-50 mg/dose parenterally 2.
Cough and Cold Symptoms
The efficacy of diphenhydramine for symptomatic treatment of upper respiratory tract infections has not been established for children younger than 6 years 2. Guidelines specifically state:
- OTC cough and cold medications containing antihistamines should not be prescribed until they have been shown to make cough less severe or resolve sooner 2
- Honey may offer more relief for cough symptoms than diphenhydramine 2
Potential for Abuse
Children and adolescents with chronic illnesses may exhibit drug-seeking behavior with diphenhydramine use 5. This risk should be considered when prescribing to older pediatric patients, particularly those with chronic conditions.
Alternative Approaches
Second-generation antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine) have been shown to be well-tolerated in young children with a very good safety profile 2. These medications should be considered as safer alternatives when antihistamine therapy is necessary in pediatric patients.
Management of Accidental Ingestion
If accidental ingestion occurs:
- Children under 6 years who ingest at least 7.5 mg/kg should be referred to an emergency department 4, 6
- Children 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 4
- Do not induce emesis or administer activated charcoal outside of a healthcare setting due to the risk of loss of consciousness or seizures 4
Key Takeaways
The evidence strongly suggests that diphenhydramine should be avoided in young children due to safety concerns. The FDA and multiple clinical guidelines have moved toward restricting its use in pediatric populations, with some countries like Germany and Sweden restricting access to first-generation antihistamines altogether 7. When antihistamine therapy is necessary in children, second-generation antihistamines should be preferred due to their superior safety profile.