Stefan Russmann1, David F Niedrig2, Mathias Budmiger3, Caroline Schmidt2, Bruno Stieger4, Sandra Hürlimann5, Gerd A Kullak-Ublick4. 1. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. Electronic address: stefan.russmann@usz.ch. 2. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland. 3. Department of Surgery, Regional Hospital Lucerne-Sursee, Sursee, Switzerland. 4. Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. 5. Institute of Pathology, Regional Hospital Lucerne, Lucerne, Switzerland.
Abstract
BACKGROUND & AIMS: Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders. Although liver injury was observed in premarketing trials of rivaroxaban, there are no published postmarketing cases of liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver injury associated with rivaroxaban, including two with liver biopsy, and search queries in three large international pharmacovigilance databases for comparable cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly probable", "probable", and "possible" cause in 4, 7, and 3 patients, respectively. Search results from three large international pharmacovigilance databases revealed a considerable number of additional hepatic adverse events where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret the presented information as a relevant safety signal that should be followed by pharmacoepidemiological studies in order to reliably estimate absolute and relative risks of liver injury associated with rivaroxaban in support of rational risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease in patients treated with rivaroxaban should be considered as a potential adverse drug reaction, and if no other likely cause can be identified rivaroxaban should be stopped as soon as possible.
BACKGROUND & AIMS:Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders. Although liver injury was observed in premarketing trials of rivaroxaban, there are no published postmarketing cases of liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver injury associated with rivaroxaban, including two with liver biopsy, and search queries in three large international pharmacovigilance databases for comparable cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly probable", "probable", and "possible" cause in 4, 7, and 3 patients, respectively. Search results from three large international pharmacovigilance databases revealed a considerable number of additional hepatic adverse events where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret the presented information as a relevant safety signal that should be followed by pharmacoepidemiological studies in order to reliably estimate absolute and relative risks of liver injury associated with rivaroxaban in support of rational risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease in patients treated with rivaroxaban should be considered as a potential adverse drug reaction, and if no other likely cause can be identified rivaroxaban should be stopped as soon as possible.
Authors: N M Intagliata; Z H Henry; H Maitland; N L Shah; C K Argo; P G Northup; S H Caldwell Journal: Dig Dis Sci Date: 2016-01-02 Impact factor: 3.199