Critical
Ciclosporin × Simvastatin
Immunosuppressants. Calcineurin inhibitors×HMG-CoA reductase inhibitors (statins)
Mechanism
Cyclosporine blocks two simvastatin clearance routes: the OATP1B1 transporter (uptake into hepatocytes) and CYP3A4. Active simvastatin levels rise 5- to 8-fold. The FDA Zocor label specifically lists cyclosporine as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
The combination is not prescribed. For transplant patients needing a statin, use pravastatin up to 20 mg/day or fluvastatin (minimal interaction with cyclosporine). Check creatine kinase every 4–6 weeks.