Major
Established
Mô tả
Cyclosporine dramatically increases atorvastatin plasma levels through combined inhibition of CYP3A4, OATP1B1, and P-gp, substantially raising the risk of myopathy and rhabdomyolysis.
Cơ chế
Atorvastatin is a substrate of CYP3A4 for metabolism, OATP1B1 for hepatic uptake, and P-gp for biliary excretion; cyclosporine inhibits all three pathways, dramatically increasing atorvastatin exposure.
Ý nghĩa lâm sàng
Atorvastatin AUC may increase 7–10-fold; numerous case reports of severe rhabdomyolysis requiring ICU admission in transplant patients.
Xử trí
If a statin is needed with cyclosporine, use pravastatin (not a CYP3A4 substrate) or fluvastatin at the lowest dose. FDA limits atorvastatin to 10 mg/day with cyclosporine.