Drug interactions between Lipitor and Rapamune

atorvastatin ↔ sirolimus

Applies to:Lipitor (atorvastatin) and Rapamune (sirolimus)

GENERALLY AVOID: Coadministration of a macrolide immunosuppressant with certain HMG-CoA reductase inhibitors may result in elevated plasma concentrations of both due to competitive inhibition of CYP450 3A4 metabolism. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity including rhabdomyolysis, which can be fatal. In one case report, severe rhabdomyolysis complicated by acute renal transplant failure occurred in a diabetic woman whose drug regimen at the time of hospital admission consisted of tacrolimus, azathioprine, prednisolone, felodipine, citalopram, aspirin, insulin, simvastatin, and fusidic acid. The patient developed muscle pain accompanied by a grossly elevated serum creatine kinase level several weeks after simvastatin was increased from 10 to 20 mg/day and fusidic acid was initiated to treat soft tissue infection and osteomyelitis of a toe. She recovered after discontinuation of simvastatin and fusidic acid and institution of supportive therapy. Simvastatin was later replaced with fluvastatin, and fusidic acid was administered on another occasion without incident. The authors suggest that use of tacrolimus with simvastatin at a dosage exceeding 10 mg/day may increase the risk of rhabdomyolysis. The use of fusidic acid may have presented an additional risk factor in the case patient. In another report, a transplant patient developed significantly elevated sirolimus serum trough levels following addition of atorvastatin to her regimen. No adverse effects were reported, but a 50% reduction in sirolimus dosage was required.

MANAGEMENT: In general, lovastatin, red yeast rice (which contains lovastatin), and simvastatin should preferably be avoided in patients treated with sirolimus or tacrolimus due to the potential for serious interaction. Atorvastatin may be used with caution, although the dosage should start low, and immunosuppressant blood levels should be closely monitored. Pravastatin and fluvastatin are probably the safest alternatives, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.