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Post-marketing reports in FAERS: liver injury with novel oral anticoagulants


Researchers at University of Bologna ( Italy ) have assessed the hepatic safety of Novel Oral AntiCoagulants ( NOACs ) analyzing the publicly available US-FDA Adverse Event Reporting System ( FAERS ).

Reports of Drug-Induced Liver Injury ( DILI ) associated with novel oral anticoagulants were extracted, including Acute Liver Failure ( ALF ) events.

DILI reports represented 3.7% ( N = 146 ) and 1.7% ( N = 222 ) of all reports for Rivaroxaban ( Xarelto ) and Dabigatran ( Pradaxa ), respectively.

No statistically significant association was found for Dabigatran, in primary and secondary analyses.

Disproportionality signals emerged for Rivaroxaban in primary analysis ( acute liver failure: N = 25; reporting odds ratios, ROR = 2.08; 95% CI = 1.34-3.08 ).

In a large proportion of drug-induced liver injury reports concomitant hepatotoxic and/or interacting drugs were recorded: 42% and 37% ( Rivaroxaban and Dabigatran, respectively ), especially statins, Paracetamol ( Acetaminophen ) and Amiodarone.

Among acute liver failure reports, fatal outcome occurred in 49% of cases ( 44% and 51%, Rivaroxaban and Dabigatran, respectively ), whereas rapid onset of the event ( less than 1 week ) was detected in 46% of patients ( 47% and 44% respectively ).

In conclusion, the disproportionality signal for Rivaroxaban calls for further comparative population-based studies to characterize and quantify the actual drug-induced liver injury risk of novel oral anticoagulants, taking into account drug- and patient-related risk factors.
As drug-induced liver injury is unpredictable, these findings strengthen the role of (a) pharmacovigilance to timely detect post-marketing signals of drug-induced liver injury through FAERS and other data sources, (b) clinicians to early assess, on a case-by-case basis, the potential responsibility of novel oral anticoagulants when they diagnose a liver injury. ( Xagena )

Raschi E et al, Br J Clin Pharmacol 2015; Epub ahead of print

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