Risk of injury associated with the sedative potential of second‐generation antihistamines: A nationwide retrospective cohort study

AIM: Individual second-generation antihistamines may possess differential sedative potential due to the variability in central histamine receptor H1 occupancy. This study aimed to evaluate whether the sedative potential of second-generation antihistamines is associated with the risk of injury during Japan's pollen season. METHODS: We conducted a retrospective cohort study using data acquired from a nationwide health insurance claims database in Japan. We enrolled patients with allergic rhinitis who were newly prescribed oral second-generation antihistamines during the pollen season (January-May) between 2006 and 2022. Antihistamines were categorized into two groups based on the estimated central histamine receptor H1 occupancy: ≥ 10% (higher-sedation group: cetirizine, levocetirizine, loratadine, olopatadine and bepotastine) and < 10% (lower-sedation group: fexofenadine, bilastine and desloratadine). The proportions of newly diagnosed injuries during the same pollen season were compared between the higher-sedation and lower-sedation groups using propensity score overlap weighting. Subgroup analysis that stratified patients by age (< 65 and ≥ 65 years) was also conducted. RESULTS: Among 1 313 550 eligible patients, 50.2% and 49.8% received higher-sedation and lower-sedation antihistamines, respectively. After overlap weighting, no significant difference in injury risk was observed between the groups (2.6% vs. 2.6%; risk difference, -0.0%; 95% confidence interval, -0.1 to 0.0; P = 0.388). Subgroup analysis showed consistent results across the age groups. CONCLUSION: In this large nationwide cohort of patients with allergic rhinitis, second-generation antihistamines with higher vs. lower sedative potential showed no difference in injury risk during Japan's pollen season.