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Br J Clin Pharmacol. 2015 Aug;80(2):285-93. doi: 10.1111/bcp.12611. Epub 2015 May 20.

Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system.

Author information

1
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
2
University of Bordeaux, U657, F33000, Bordeaux, France.
3
INSERM U657, F33000, Bordeaux, France.
4
CIC Bordeaux CIC1401, F33000, Bordeaux, France.
5
Department of Public Health and Community Medicine, University of Verona, Verona, Italy.

Abstract

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.

KEYWORDS:

FAERS; disproportionality; hepatotoxicity; liver injury; novel oral anticoagulants; spontaneous reporting system

PMID:
25689417
PMCID:
PMC4541976
DOI:
10.1111/bcp.12611
[Indexed for MEDLINE]
Free PMC Article

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