Drug interactions between fluconazole and Lipitor

fluconazole ↔ atorvastatin

Applies to:fluconazole and Lipitor (atorvastatin)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 including azole antifungal agents may significantly increase the plasma concentrations of HMG-CoA reductase inhibitors that are substrates of the isoenzyme. 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. Within the azole class, ketoconazole and itraconazole are considered the most potent inhibitors, while fluconazole is comparatively weak and generally causes clinically significant interactions with CYP450 3A4 substrates only at dosages of 200 mg/day or more.

MANAGEMENT: Given the potential for serious and life-threatening musculoskeletal toxicity associated with increased plasma levels of HMG-CoA reductase inhibitors, the concomitant use of atorvastatin, lovastatin, or simvastatin with azole antifungal agents should be avoided. Caution is recommended for patients receiving azole antifungal agents and red yeast rice, which contains lovastatin. Fluvastatin and pravastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. Alternatively, an interruption of the statin may be considered during treatment with an azole antifungal agent. 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.