Methods: PubMed and cross references were searched to identify double-blind placebo-controlled clinical trials. Studies were selected that used the standardized 100-km on-road highway driving test in normal traffic to examine driving performance. Patient studies were excluded. Subjects are instructed to maintain a steady lateral position and a constant speed (95 km/h). The Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car, is the primary outcome measure of the test. The magnitude of driving impairment for antihistamine drugs was compared to SDLP increments seen at Blood Alcohol Concentration (BAC) 0.05% (DSDLP= +2.4 cm) and BAC 0.08% (DSDLP= +4.3 cm), i.e. the most common legal limits for driving.
Results: Eighteen studies were included. Regarding acute effects, impairment greater than BAC 0.08% was found after single dosages of diphenhydramine, emedastine, and hydroxyzine. Impairment after clemastine, triprolidine, mizolastine, acrivastine, dexchlorpheniramine, and mequitazine was comparable to BAC 0.05%. Results for cetirizine were mixed. No significant impairment was found for terfenadine, loratadine, levocetirizine, desloratadine, ebastine, bilastine, fexofenadine and rupatadine. Regarding sub-chronic effects (4-8 days of daily drug treatment), significant driving impairment was found for emedastine, diphenhydramine, clemastine, triprolidine, ebastine, and hydroxyzine. Mixed results were found for cetirizine, terfenadine and loratadine. No significant driving impairment was found for levocetirizine, acrivastine, fexofenadine, dexchlorpheniramine, bilastine, and mequitazine.
Discussion: Antihistamine drugs may significantly impair driving performance. Impairment is often seen with acute use of first- and second-generation antihistamines, and the magnitude of impairment is comparable to that seen at legal BAC limits for driving. Tolerance to the impairing effect after chronic daily use of antihistamines develops slowly. The newer antihistamines levocetirizine, fexofenadine and desloratadine did not significantly impair driving performance.