Severe rhabdomyolysis induced by possible drug-drug interaction between Ribociclib and Simvastatin

Drug-drug interactions with cyclin-dependent kinases inhibitors 4 and 6 (CDK4/6) are known and should be taken into account.

A 68-year-old woman, on prior Simvastatin therapy, developed severe rhabdomyolysis after three weeks of Ribociclib initiation. She showed general weakness with mobility problems and was admitted to our hospital.

Ribociclib and Simvastatin were discontinued and the patient received intensive intravenous hydration. She finally recovered her mobility after two weeks.

We hypothesize that Simvastatin induced rhabdomyolysis by possible interaction with Ribociclib. Ribociclib is a strong inhibitor of CYP 3A4 and a potential inhibitor of OATP1B1 membrane transporter. Simvastatin plasma concentration may reach toxic levels due to Ribociclib inhibition. To assess the relevance of our hypothesis, we used the Drug Interaction Scale. With a total score of 7, the interaction is considered as "probable." Because of the high risk of severe rhabdomyolysis, the concomitant use of Simvastatin with Ribociclib should be avoided or otherwise careful monitoring of creatine kinase is warranted.