Why Benadryl (Diphenhydramine) Has Fallen Out of Favor for Children
Benadryl should generally be avoided in all children below 6 years of age due to lack of proven efficacy for common cold symptoms, significant toxicity risk from overdose, and the availability of safer second-generation antihistamines for allergic conditions. 1
Primary Safety Concerns
Lack of Efficacy and Safety Data for Young Children
The efficacy of diphenhydramine for symptomatic treatment of upper respiratory tract infections has not been established for children younger than 6 years. 1
Controlled trials have demonstrated that antihistamine-decongestant combination products are not effective for symptoms of upper respiratory tract infections in young children. 1
In 2007, the FDA's Nonprescription Drugs and Pediatric Advisory Committees recommended that OTC medications used to treat cough and cold no longer be used for children below 6 years of age. 1
Significant Mortality and Toxicity Risk
Between 1969 and September 2006, there were 69 fatalities associated with antihistamines in children ≤6 years of age, with diphenhydramine accounting for 33 deaths (48% of antihistamine-related deaths), and 41 deaths occurring in children below age 2 years. 1
Drug overdose and toxicity were common events, resulting from use of multiple cold/cough products, medication errors, accidental exposures, and intentional overdose. 1
Children less than 6 years of age who ingest at least 7.5 mg/kg of diphenhydramine should be referred to an emergency department due to toxicity risk. 2
Death can occur even from topical application in toddlers, demonstrating the drug's narrow therapeutic window in young children. 3
Common Adverse Effects in Children
The most common adverse events in pediatric diphenhydramine exposures include tachycardia (53.4%), hallucinations (46.5%), somnolence (34.7%), agitation (33.9%), and mydriasis (26.3%). 4
Seizures occurred in 5.5% of cases, and excitability may occur, especially in children. 5, 4
The majority (79.5%) of diphenhydramine-only adverse event cases occurred in children 2 to <4 years of age, with 74.7% involving accidental unsupervised ingestions. 4
Safer Alternatives Available
Second-Generation Antihistamines
Second-generation antihistamines such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine when used in young children have been shown to be well tolerated and to have a very good safety profile. 1
These agents provide effective antihistamine action without the significant sedation and anticholinergic effects of diphenhydramine. 1
Limited Role in Specific Clinical Scenarios
Anaphylaxis Management
Diphenhydramine retains a role as second-line therapy in anaphylaxis management at doses of 1 to 2 mg/kg or 25 to 50 mg per dose (parenterally). 1
H1 antihistamines are considered second-line therapy to epinephrine and should never be administered alone in the treatment of anaphylaxis. 1
These agents have a much slower onset of action than epinephrine. 1
FDA Labeling Restrictions
The FDA label explicitly states "do not use to make a child sleepy" and directs that children under 6 years of age should "Do not use" for the standard oral formulation. 5
The label warns about marked drowsiness, excitability especially in children, and the need to keep out of reach of children due to overdose risk. 5
Clinical Bottom Line
The shift away from diphenhydramine in pediatrics reflects the convergence of three critical factors: demonstrated lack of efficacy for common indications (upper respiratory infections), significant mortality and morbidity from accidental and intentional overdoses, and the availability of safer second-generation antihistamines with superior safety profiles. 1, 4 For allergic conditions requiring antihistamine therapy, second-generation agents should be first-line, and for anaphylaxis, diphenhydramine remains only adjunctive to epinephrine. 1