Drug Interactions between atorvastatin and danazol

ADJUST DOSE: The use of danazol with higher dosages of certain HMG-CoA reductase inhibitors may be associated with an increased risk of myopathy. The proposed mechanism is danazol inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the metabolic clearance of HMG-CoA reductase inhibitors like atorvastatin, lovastatin, simvastatin, as well as some of their pharmacologically active metabolites. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. Use of simvastatin and lovastatin with danazol has resulted in musculoskeletal toxicity, and the risk may be increased with dosages greater than 10 and 20 mg/day, respectively.

MANAGEMENT: The benefits of the use of atorvastatin, lovastatin, simvastatin, and red yeast rice (which contains lovastatin) in patients receiving danazol should be carefully weighed against the potential risks. If the combination is prescribed, lower dosages of the HMG-CoA reductase inhibitor should be considered. For example, lovastatin therapy should begin at 10 mg/day and not exceed 20 mg/day when prescribed with danazol. Fluvastatin, pravastatin, and rosuvastatin are probably safer alternatives in patients receiving danazol, 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.