In infants and children, the side effects of first-generation over-the-counter (OTC) antihistamines, such as diphenhydramine (Benedryl) and hydroxyzine (Atarax), can include:

Typically, first-generation OTC antihistamines have a sedating effect because of passage into the CNS. However, in some individuals, especially infants and children, paradoxical CNS stimulation occurs and is manifested by excitement, euphoria, restlessness, and confusion. For this reason, use of first-generation OTC antihistamines has declined and second-generation product use has increased. Reye's syndrome is a systemic response to a virus. First-generation OTC antihistamines do not exhibit a cholinergic effect. Nausea and diarrhea are uncommon with first-generation OTC antihistamines.