Critical
Ciclosporin × Rosuvastatin
Immunosuppressants. Calcineurin inhibitors×HMG-CoA reductase inhibitors (statins)
Mechanism
Cyclosporine blocks the OATP1B1 transporter, the uptake route of rosuvastatin into hepatocytes. Rosuvastatin levels rise 7-fold. This is unique among statins: other cyclosporine–statin pairs go through CYP3A4, but rosuvastatin barely uses CYP3A4 – OATP1B1 drives the risk.
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. Check creatine kinase at 4–6 weeks.