The drug risks of cilostazol: A pharmacovigilance study of FDA Adverse Event Reporting System database

Cilostazol is indicated for alleviating intermittent claudication (IC) in stable-phase peripheral arterial disease (PAD) patients. Conducting data mining on adverse events (AEs) of cilostazol in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to explore its potential medication risks and advance more rational and secure clinical medication practices.

This study utilized the Open Vigil 2.1-MedDRA tool to retrieve and extract AE reporting data related to cilostazol from the FAERS database spanning the first quarter of 2004 to the first quarter of 2024. The primary methodology employed was the application of the reporting odds ratio (ROR) method to detect risk signals associated with AEs of cilostazol.

A total of 2,130 AE reports involving cilostazol were identified as the primary suspect drug, with a total of 7,134 AEs reported. These reports were predominantly concentrated among patients aged 60 and above, with a higher occurrence in males compared to females. Japan ranked first among the reporting countries, and the majority of reports were submitted by healthcare professionals. Through the screening of cilostazol, a total of 323 positive risk signals for AEs were identified, encompassing 23 system organ classes (SOCs). A comparison with the existing cilostazol product label revealed 8 AEs that were not included based on the number of AE reports, and 19 AEs that were not included based on the strength of the risk signals. Cilostazol exhibited positive risk signals for AEs primarily affecting 8 organ systems based on the SOC classification. Among these, cardiac disorders ranked highest, with a total of 53 positive risk signals for cardiovascular-related AEs identified. In terms of the number of reports, cardiac failure ranked first, aligning with the black box warning issued by the FDA regarding cilostazol. The occurrence of adverse reactions related to cilostazol is primarily concentrated within the first month of treatment. However, a certain proportion of adverse reactions have been reported to occur after long-term use (exceeding 360 days) of cilostazol therapy.

Our results have further enriched the observations from existing clinical and real-world studies, uncovering new AE signals for cilostazol, including fall, cerebral infarction, pneumonia, loss of consciousness, acute kidney injury, renal impairment, renal failure, cardiac vein perforation, basal ganglia haematoma, cerebral hyperperfusion syndrome, et al. This study also highlights the significant impact of cilostazol on the cardiovascular system, necessitating close attention to potential cardiovascular toxicities. In addition to focusing on the short-term adverse reactions following cilostazol administration, thorough research into its long-term safety profile is also imperative. This study provides recommendations and guidance for the rational and safe clinical use of cilostazol. In the future, prospective studies are needed to explore the occurrence of related AEs further.