Rivaroxaban postmarketing risk of liver injury.

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.

[Adverse reactions and risks associated with non compliance].

Non compliance is a frequent and underestimated problem in clinical practice, that is associated with considerable risks, adverse reactions and costs. Next to omitting one or several doses with consequent lack of efficacy, other forms of non compliance can be described. These include administration of a wrong dose or at a wrong time, early termination of therapy or also its unwarranted continuation, and self-administered comedication without consideration of potential interactions.

Current concepts of mechanisms in drug-induced hepatotoxicity.

Drug-induced liver injury (DILI) has become a leading cause of severe liver disease in Western countries and therefore poses a major clinical and regulatory challenge. Whereas previously drug-specific pathways leading to initial injury of liver cells were the main focus of mechanistic research and classifications, current concepts see these as initial upstream events and appreciate that subsequent common downstream pathways and their attenuation by drugs and other environmental and genetic factors also have a profound impact on the risk of an individual patient to develop overt liver disease. This review summarizes current mechanistic concepts of DILI in a 3-step model that limits its principle mechanisms to three main ways of initial injury, i.