Interactions between posaconazole and Baycol (cerivastatin)
cerivastatin and posaconazole (Major Drug-Drug)
ADJUST DOSE: Coadministration with posaconazole may significantly increase the plasma concentrations of HMG-CoA reductase inhibitors that are metabolized by CYP450 3A4 such as atorvastatin, cerivastatin, lovastatin, simvastatin, and red yeast rice (which contains lovastatin). The mechanism is decreased clearance due to inhibition of CYP450 3A4 by posaconazole. Although clinical data are lacking, the interaction has been reported with other inhibitors of CYP450 3A4, including other azole antifungal agents. 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.
MANAGEMENT: During concomitant therapy with posaconazole, lower dosages are recommended for HMG-CoA reductase inhibitors that are primarily metabolized by CYP450 3A4. Alternatively, fluvastatin, pravastatin, and rosuvastatin may be considered, 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.
