Antihistamine Use in Infants
Critical Safety Recommendation
Diphenhydramine should NOT be used in infants or children under 6 years of age for routine allergic symptoms due to significant safety concerns, including 33 documented deaths in children under 6 years between 1969-2006. 1 The FDA label explicitly states "Do not use" for children under 6 years of age. 2
First-Line Treatment: Second-Generation Antihistamines
For infants and young children requiring antihistamine therapy, second-generation antihistamines (cetirizine, loratadine, desloratadine, fexofenadine, levocetirizine) are the recommended first-line agents due to their superior safety profile and lack of sedating effects. 3, 1
Specific Dosing for Infants and Young Children
Cetirizine: 2.5 mg once or twice daily for children aged 2-5 years 1
Loratadine: 5 mg once daily for children aged 2-5 years 1
Why Second-Generation Antihistamines Are Preferred
- Significantly better safety profile with very low rates of serious adverse events in young children 3, 1
- Non-sedating, avoiding the learning impairment and excessive drowsiness seen with first-generation agents 3
- No cytochrome P450 interactions that could lead to dangerous drug-drug interactions 3
- No cardiotoxicity risk unlike withdrawn agents (terfenadine, astemizole) 3
When Antihistamines Should NOT Be Used in Infants
Oral H1-antihistamines should NOT be administered to infants with atopic dermatitis and/or family history of allergy or asthma for the prevention of wheezing or asthma. 3 This recommendation prioritizes avoiding side effects over uncertain preventive benefits. 3
Limited Role of First-Generation Antihistamines
Diphenhydramine: Restricted Emergency Use Only
Diphenhydramine should be reserved exclusively for emergency anaphylaxis management in children over 6 years, and only as second-line therapy after epinephrine. 1, 5
- Emergency dosing (children >6 years only): 1-2 mg/kg per dose, maximum 50 mg 1, 5
- Never administer diphenhydramine alone in anaphylaxis—epinephrine is the primary treatment 1
- Between 1969-2006, there were 69 total antihistamine-related deaths in children under 6 years, with diphenhydramine responsible for 33 of these fatalities 3, 1
Why First-Generation Antihistamines Are Problematic
- Sedation occurs in >50% of children at therapeutic doses, impairing learning and daily function 6
- Anticholinergic and antimuscarinic side effects persist even when tolerance to sedation develops 3
- No proven benefit for pruritus in controlled trials, with symptom relief primarily due to sedation rather than antipruritic effects 3
- FDA advisory committees recommended against use in children under 6 years for OTC cough and cold preparations 3, 1
Common Clinical Pitfalls to Avoid
- Do not use antihistamines "to make a child sleepy"—this is explicitly contraindicated per FDA labeling 2
- Avoid OTC combination cough and cold products in children under 6 years due to overdose risk and lack of efficacy 3, 1
- Do not assume antihistamines improve sleep architecture—limited evidence shows diphenhydramine may not reduce nighttime awakenings and children develop tolerance to sedating effects 3
- Liquid formulations are preferred in young children for easier administration and better absorption 1
Conditions Where Antihistamines May Be Appropriate in Infants
While prevention of asthma/wheezing is not indicated, the ARIA guidelines acknowledge that antihistamines may be used for other conditions such as urticaria in infants when clinically necessary. 3 In such cases, second-generation agents remain the preferred choice. 3
Special Consideration: Mastocytosis
In the rare condition of pediatric cutaneous mastocytosis, both sedating and non-sedating H1 antihistamines (including diphenhydramine, hydroxyzine, and cetirizine) have proven useful for controlling pruritus, flushing, urticaria, and tachycardia. 3 This represents a specific exception where first-generation agents may be considered under specialist supervision. 3