H1 antihistamine-induced adverse events and time to onset: A retrospective analysis using the Japanese Adverse Drug Event Report Database

H1 antihistamines have not been systematically evaluated for adverse events (AEs) in real-world settings despite their widespread use in Japan. We investigated the characteristics of AEs caused by H1 antihistamines using the Japanese Adverse Drug Event Report (JADER) database. We extracted 14 common AEs (including similar AEs) with a high frequency from the JADER database (April 2004 ‒ September 2023) for patients taking H1 antihistamines as "suspected drugs". Adjusted reporting odds ratios (aRORs) for sex and age were calculated to identify possible H1 antihistamines. A time-event analysis was performed using a Weibull distribution. Among the 32,592 case reports where H1 antihistamines were identified as "suspected drugs", a total of 9,549 case reports involving 2,881 patients were extracted for the common 14 AEs associated with 6 first-generation and 16 second-generation drugs. Among these patients, 53.6% were female, and patients aged 50 - 79 years had a high incidence (45.7%). The highest aROR was for alopecia (56.6), followed by angioedema (3.2), hepatotoxicity (2.6), loss of consciousness (2.4), and Stevens-Johnson syndrome (2.1). Anaphylaxis, Stevens-Johnson syndrome, drug/toxic eruption, angioedema, and convulsions/epilepsy occurred within 1 week of H1 antihistamine use. Hepatotoxicity, loss of consciousness, convulsion/epilepsy, pneumonia and aplastic anemia occurred over time throughout H1 antihistamine treatment. The shape parameter β values of most AEs were < 1.0. This study revealed that most severe AEs, such as anaphylaxis and toxic cutaneous diseases, caused by H1 antihistamines occurred within 1 week of treatment. Hepatotoxicity, alopecia, interstitial pneumonia, and aplastic anemia occurred throughout the treatment period.