Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

Background
All antihistamines are capable of crossing the blood-brain barrier and thus may cause sedation. Most antihistamine users are ambulatory patients and therefore presumably drive a car.
Objective
To summarize the effects of antihistamine drugs on driving ability.
Data Sources and Study Selection
A literature search (MEDLINE and cross-references) was performed using the keywords driving and antihistamine. Sixteen studies using the on-the-road driving test during normal traffic were included in the review. Studies were double-blind and placebo-controlled and included a positive control.
Results
First-generation antihistamines (diphenhydramine, triprolidine, terfenadine, dexchlorpheniramine, clemastine) significantly impair driving performance after both one-time and repeated (daily) administration. Second-generation antihistamines (cetirizine, loratadine, ebastine, mizolastine, acrivastine, emedastine, mequitazine) may also impair driving performance, but the magnitude and extent of impairment depend on the administered dose, sex, and time between testing and treatment administration. Tolerance develops after 4 to 5 days of administration, but impairment is not absent. Third-generation antihistamines (fexofenadine and levocetirizine) have been shown to produce no driving impairment after both one-time and repeated administration.
Conclusions
First- and second-generation antihistamines may significantly impair driving performance. In the context of driving safety but also taking into account the cardiotoxic properties of some of the second-generation antihistamines, we advise treating patients with third-generation antihistamines such as fexofenadine and levocetirizine.