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Liver injury with novel oral anticoagulants: assessing post‐marketing reports in the US Food and Drug Administration adverse event reporting system
Author(s) -
Raschi Emanuel,
Poluzzi Elisabetta,
Koci Ariola,
Salvo Francesco,
Pariente Antoine,
Biselli Maurizio,
Moretti Ugo,
Moore Nicholas,
De Ponti Fabrizio
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12611
Subject(s) - adverse event reporting system , medicine , dabigatran , rivaroxaban , pharmacovigilance , postmarketing surveillance , odds ratio , adverse effect , confidence interval , concomitant , pharmacoepidemiology , population , emergency medicine , pharmacology , warfarin , atrial fibrillation , environmental health , medical prescription
Aim We assessed the hepatic safety of novel oral anticoagulants (NOACs) analyzing the publicly available US‐FDA adverse event reporting system (FAERS). Methods We extracted reports of drug‐induced liver injury (DILI) associated with NOACs, including acute liver failure (ALF) events. Based on US marketing authorizations, we performed disproportionality analyses, calculating reporting odds ratios (RORs) with 95% confidence interval (CI), also to test for event‐ and drug‐related competition bias, and case‐by‐case evaluation for concomitant medications. Results DILI reports represented 3.7% ( n = 146) and 1.7% ( n = 222) of all reports for rivaroxaban and dabigatran, respectively. No statistically significant association was found for dabigatran, in primary and secondary analyses. Disproportionality signals emerged for rivaroxaban in primary analysis (ALF: n = 25, ROR = 2.08, 95% CI 1.34, 3.08). In a large proportion of DILI reports concomitant hepatotoxic and/or interacting drugs were recorded: 42% and 37% (rivaroxaban and dabigatran, respectively), especially statins, paracetamol and amiodarone. Among ALF reports, fatal outcome occurred in 49% of cases (44% and 51%, rivaroxaban and dabigatran, respectively), whereas rapid onset of the event (<1 week) was detected in 46% of patients (47% and 44%, respectively). Conclusions The disproportionality signal for rivaroxaban calls for further comparative population‐based studies to characterize and quantify the actual DILI risk of NOACs, taking into account drug‐ and patient‐related risk factors. As DILI is unpredictable, our findings strengthen the role of (a) timely pharmacovigilance to detect post‐marketing signals of DILI through FAERS and other data sources, (b) clinicians to assess early, on a case‐by‐case basis, the potential responsibility of NOACs when they diagnose a liver injury.