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

Int J Clin Pharmacol Ther. 2025 Apr 22. doi: 10.5414/CP204707. Online ahead of print.

ABSTRACT

BACKGROUND: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

PMID:40260600 | DOI:10.5414/CP204707