ribociclib and Rhabdomyolysis

A woman in her 50s with metastatic hormone receptor positive breast cancer developed rhabdomyolysis and subsequent acute kidney injury while on a combination of ribociclib and rosuvastatin therapy. She had been taking both medications long term and had recently recommenced her ribociclib at her usual dose after a routine 1 week break. Cyclin-dependent kinase 4/6 inhibitors have been implicated in causing rhabdomyolysis by potentiating statin effect by way of inhibition of cytochrome P450 enzymatic action and decreasing hepatic membrane transporter function. This is the first case in which the combination of ribociclib and rosuvastatin has been shown to cause this adverse effect. It is also one of the first to demonstrate this effect occurring years after commencement of therapy. Continued vigilance for this side effect should be maintained long term.

Topics: Aminopyridines; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Purines; Rhabdomyolysis; Rosuvastatin Calcium

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.

Topics: Aged; Aminopyridines; Creatine Kinase; Drug Interactions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Purines; Rhabdomyolysis; Severity of Illness Index; Simvastatin