Disproportionality analysis of amenamevir-induced encephalopathy using the Japanese adverse drug event report database

Tomoyuki Yamada; Taku Ogawa; Tomoko Tanaka; Yusuke Kusaka; Masami Nishihara; Akira Ashida

doi:10.1016/j.jiac.2024.09.008

Disproportionality analysis of amenamevir-induced encephalopathy using the Japanese adverse drug event report database

J Infect Chemother. 2024 Sep 12:S1341-321X(24)00259-9. doi: 10.1016/j.jiac.2024.09.008. Online ahead of print.

Authors

Tomoyuki Yamada¹, Taku Ogawa², Tomoko Tanaka³, Yusuke Kusaka⁴, Masami Nishihara⁵, Akira Ashida⁶

Affiliations

¹ Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan; Infection Control Center, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan. Electronic address: tomoyuki.yamada.cd@ompu.ac.jp.
² Infection Control Center, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan; Department of Microbiology and Infection Control, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
³ Infection Control Center, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan; Department of Pediatrics, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan.
⁴ Infection Control Center, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan; Department of Intensive Care Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
⁵ Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
⁶ Department of Pharmacy, Osaka Medical and Pharmaceutical University Hospital, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan; Department of Pediatrics, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-Machi, Takatsuki, Osaka, 569-8686, Japan.

PMID: 39276861
DOI: 10.1016/j.jiac.2024.09.008

Abstract

Introduction: Anti-herpesvirus drug-induced encephalopathy can complicate herpes zoster treatment; however, the association between the recently developed anti-herpesvirus drug amenamevir and encephalopathy development remains unknown. Determining the characteristics of amenamevir-induced encephalopathy is essential for potentially improving patient outcomes in the treatment of herpes zoster. The aim of this study is to identify the association between amenamevir treatment and encephalopathy and to determine the risk factors for amenamevir-induced encephalopathy via disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database.

Method: We conducted a retrospective observational study using anonymized data from the JADER database. Encephalopathy was defined according to the Standardized Medical Dictionary for Regulatory Activities Queries specific to "Noninfectious encephalopathy/delirium." Disproportionality analysis was used to calculate the reporting odds ratios (RORs) and 95 % confidence intervals (CIs) to assess associations between amenamevir and encephalopathy. Multivariable logistic regression considered age, gender, chronic kidney disease, and cytochrome P450 3A inhibitor use as potential risk factors.

Results: Out of 713,316 patients, 246 were prescribed amenamevir. The median onset of encephalopathy in these patients was 3 days. Disproportionality of encephalopathy was observed in patients treated with amenamevir (ROR, 3.44; 95 % CI, 2.48-4.78). Furthermore, multivariable logistic regression analysis suggested that an age of ≥70 years was associated with amenamevir-induced encephalopathy (ROR, 7.63; 95 % CI, 2.25-25.9).

Conclusion: These results suggest that amenamevir treatment may be associated with encephalopathy, particularly in patients aged ≥70 years. Healthcare providers should be aware of this potential risk, especially in elderly patients, to prevent severe central nervous system complications.

Keywords: Adverse event; Amenamevir; Encephalopathy; Pharmacovigilance.

Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.