Association of Clopidogrel with Interstitial Lung Disease: Gaining Insight Through the Japanese Pharmacovigilance Database

Mariko Kozaru, Hiroko Kambara, Akari Higuchi, Tatsuki Kagatsume, Keiko Hosohata Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, 569-1094, JapanCorrespondence: Keiko Hosohata, Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan, Tel +81-72-690-1271, Fax +81-72-690-362, Email [email protected]: The P2Y12 receptor inhibitors clopidogrel and prasugrel are widely used. Clopidogrel and prasugrel have different metabolic pathways, but whether their adverse event (AE) profiles differ significantly is unclear.Objective: This study aimed to compare the possible AEs induced by clopidogrel and prasugrel and to assess the rank-order of their AEs submitted to a spontaneous reporting database.Materials and Methods: Data were extracted from the Japanese Adverse Drug Event Report database (JADER). Reports of AEs associated with clopidogrel and prasugrel were analyzed to calculate the reporting odds ratios (RORs) and 95% confidence intervals (CIs).Results: Based on 5869 reports for clopidogrel (69.6%, men) and 513 reports for prasugrel (74.1%, men), 703 and 135 different AEs were identified, respectively. Bleeding complications including hemorrhage were commonly reported for both clopidogrel and prasugrel. As for AEs related to clopidogrel, unexpected AEs such as interstitial lung disease (227 reports; ROR, 1.77; 95% CI, 1.49– 2.10), abnormal hepatic function (137 reports; ROR, 1.27; 95% CI, 1.07– 1.51), and hepatocellular injury (96 reports; ROR, 120.0; 95% CI, 94.9– 151.8) ranked at relatively high positions based on the number of occurrences, unlike prasugrel.Conclusion: This analysis of the national pharmacovigilance database highlights distinct AE profiles for clopidogrel and prasugrel. Unexpected AEs associated with clopidogrel were identified, providing valuable insights for clinical monitoring and patient safety.Keywords: P2Y12 platelet inhibitor, pharmacovigilance, adverse events, reporting odds ratio, signal detection, spontaneous reporting system