From the Guidelines
Fluvastatin and pravastatin are the preferred statins for patients taking cyclosporin as they have minimal interaction with this immunosuppressant medication. These two statins undergo different metabolic pathways than other statins, with fluvastatin primarily metabolized by CYP2C9 and pravastatin undergoing minimal hepatic metabolism 1. When cyclosporin and most statins are used together, cyclosporin inhibits the CYP3A4 enzyme and transporters like OATP1B1, which can lead to increased statin blood levels and higher risk of myopathy or rhabdomyolysis. Some key points to consider when using statins with cyclosporin include:
- The combination of rosuvastatin, atorvastatin, fluvastatin, or pravastatin with cyclosporin may be considered, but with caution and close monitoring 1
- The dose of atorvastatin >10 mg daily when coadministered with cyclosporin is not recommended without close monitoring of creatinine kinase and signs or symptoms of muscle-related toxicity 1
- Even with fluvastatin and pravastatin, caution is still advised, and lower starting doses are recommended (pravastatin 10-20mg daily or fluvastatin 20mg daily) 1
- Regular monitoring for muscle pain, weakness, or tenderness is important, and liver function and creatine kinase should be checked periodically Other statins like atorvastatin, simvastatin, and rosuvastatin should be avoided or used at significantly reduced doses with close monitoring if absolutely necessary in cyclosporin-treated patients 1.
From the Research
Statins and Cyclosporin Interactions
- The interaction between statins and cyclosporin is a significant concern due to the increased risk of myotoxicity 2, 3, 4.
- Cyclosporin inhibits CYP3A4, P-glycoprotein, and organic anion transporting polypeptide 1B1 (OATP1B1), which can increase the plasma concentrations of statins 2, 5.
- Statins that are metabolized by CYP3A4, such as simvastatin, lovastatin, and atorvastatin, are more likely to interact with cyclosporin 2, 4.
- However, some statins, such as pravastatin, rosuvastatin, and pitavastatin, are excreted mainly unchanged and their plasma concentrations are not significantly increased by pure CYP3A4 inhibitors like cyclosporin 2.
- Fluvastatin, which is metabolized by CYP2C9, may also be less subject to interaction with cyclosporin 4.
Statins with Lower Interaction Potential
- Pravastatin, rosuvastatin, and pitavastatin may have a lower interaction potential with cyclosporin due to their pharmacokinetic properties 2, 3.
- Fluvastatin may also be a suitable option due to its metabolism by CYP2C9, which is less affected by cyclosporin 4.
- However, it is essential to note that the interaction between statins and cyclosporin can be complex and may involve multiple mechanisms, including inhibition of hepatic uptake and biliary excretion 5, 6.