title: Benefit/risk ratio of the antihistamines (H1-receptor antagonists) terfenadine and chlorpheniramine in children.
abstract: There are few objective studies of the benefit/risk ratio of H1-receptor antagonists in children. We hypothesized that terfenadine would provide as effective peripheral H1 blockade as chlorpheniramine in young patients, but would cause less central nervous system dysfunction. We tested this hypothesis with epicutaneous histamine tests to monitor peripheral H1 blockade, P300-event-related potentials as a measure of cognitive processing, and a visual analog scale for somnolence, in a double-blind, single-dose, placebo-controlled, three-way crossover study in 15 children with allergic rhinitis (mean age, 8.5 +/- 1.4 years). On 3 different days the children received terfenadine, 60 mg, chlorpheniramine, 4 mg, or placebo; the tests were performed before and 2 to 2 1/2 hours after dosing. Both terfenadine and chlorpheniramine suppressed the histamine-induced wheal and flare compared with baseline and with placebo; terfenadine was significantly more effective (p < 0.05). Terfenadine did not increase the latency of P300-event-related potentials at the parietal (Pz) or frontal (Fz) scalp electrodes compared with baseline, in contrast to chlorpheniramine and placebo, which did increase P300 latency. Terfenadine and placebo did not increase somnolence compared with baseline, but chlorpheniramine did. In children, as previously documented in adults, terfenadine has a more favorable benefit/risk ratio than chlorpheniramine, as shown by production of significantly greater peripheral histamine blockade and significantly less central nervous system dysfunction.
authors.affiliation: Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: F E
authors.initials: FE
authors.lastname: Simons
authors.forename: J D
authors.initials: JD
authors.lastname: Reggin
authors.forename: J R
authors.initials: JR
authors.lastname: Roberts
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D002648:Child; D002744:Chlorpheniramine / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D016593:Terfenadine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002744:Chlorpheniramine; D016593:Terfenadine