MAJOR — Use With Caution
FDA-documented interaction. Consider temporary statin discontinuation or dose reduction during fluconazole treatment.
Evidence level: STRONG
Fluconazole (Diflucan) can increase simvastatin levels in your blood, raising the risk of muscle damage. Your doctor should either temporarily stop your statin or use an alternative antifungal.
Fluconazole inhibits CYP3A4 and CYP2C9. Simvastatin is a CYP3A4 substrate. Increased simvastatin exposure raises rhabdomyolysis risk. FDA simvastatin label warns about azole antifungals.
Tell your doctor you take simvastatin before starting fluconazole. A short statin holiday during antifungal treatment is usually the safest approach.
Take Simvastatin in the evening when hepatic cholesterol synthesis peaks (exception: atorvastatin and rosuvastatin have long half-lives and can be taken any time). Fluconazole can be taken at a separate meal. Report unexplained muscle pain, weakness, or dark urine immediately.
Higher risk with: liver impairment, genetic CYP enzyme variations (poor or ultra-rapid metabolizers), older age, polypharmacy (many medications).
Muscle pain or tenderness, weakness, dark urine, nausea
Discuss temporary statin suspension or alternative antifungal. If statin is continued, use lowest dose and watch for muscle symptoms.
Statin interactions often involve liver enzyme competition. Ask your doctor about alternative statins (rosuvastatin and pravastatin have fewer CYP interactions) or spacing doses 12 hours apart. CoQ10 supplementation may help with statin-related muscle discomfort.
Fluconazole (Diflucan) can increase simvastatin levels in your blood, raising the risk of muscle damage. Your doctor should either temporarily stop your statin or use an alternative antifungal.
Take Simvastatin in the evening when hepatic cholesterol synthesis peaks (exception: atorvastatin and rosuvastatin have long half-lives and can be taken any time). Fluconazole can be taken at a separate meal. Report unexplained muscle pain, weakness, or dark urine immediately.
Muscle pain or tenderness, weakness, dark urine, nausea
Statin interactions often involve liver enzyme competition. Ask your doctor about alternative statins (rosuvastatin and pravastatin have fewer CYP interactions) or spacing doses 12 hours apart. CoQ10 supplementation may help with statin-related muscle discomfort.
Discuss temporary statin suspension or alternative antifungal. If statin is continued, use lowest dose and watch for muscle symptoms.
Or browse the full interaction database (121,000+ pairs).