Rifampin-induced fluvastatin toxicity: a case report and review of literature

Fluvastatin is extensively metabolized by CYP2C9, which is induced by rifampin over several weeks, leading to a concentration decline. However, since rifampin is a potent inhibitor of the primary first-pass hepatic statin uptake transporter, the organic anion transporting polypeptide 1B1 (OATP1B1), simultaneous administration has been shown to significantly increase statin exposure. We report a previously fluvastatin-tolerant 63-year-old woman with nonalcoholic steatohepatitis who developed statin-induced rhabdomyolysis four weeks after the initiation and co-administration of rifampin for tuberculosis. After both medications were stopped, the patient showed clinical and biochemical improvement. While this report is the first to describe a clinical outcome of this interaction, multiple pharmacokinetic studies have demonstrated opposing, time-dependent rifampin effects on statin concentrations. Safe management of this challenging interaction includes statin dose reduction and/or separate administration upon rifampin initiation until the anticipated onset of CYP induction, followed by careful and gradual dose titration with monitoring of both effectiveness and toxicity.