Can fluconazole (antifungal agent) 450mg per week pulse therapy be given to a patient on rosuvastatin (statin) 5mg daily?

Fluconazole and Rosuvastatin Interaction: Safety Assessment

Fluconazole 450mg weekly pulse therapy should not be administered to patients taking rosuvastatin 5mg daily due to the risk of rhabdomyolysis from potential drug-drug interactions.

Mechanism of Interaction

• Fluconazole is an azole antifungal that inhibits cytochrome P450 enzymes, including CYP3A4, which can increase statin blood levels 1
• While rosuvastatin undergoes minimal metabolism via the cytochrome P450 system compared to other statins, it still has potential for interactions with fluconazole 2, 3
• Studies have shown that even moderate CYP3A4 inhibitors like fluconazole can lead to rhabdomyolysis in patients on statin therapy 4

Evidence of Risk

• Case reports document rhabdomyolysis occurring when fluconazole was added to statin therapy, including a case where rhabdomyolysis developed just 2 weeks after initiating fluconazole in a patient on stable statin therapy 5, 4
• Pharmacokinetic studies have shown that single doses of fluconazole produce statistically significant interactions with rosuvastatin 3
• The interaction between azole antifungals and statins is recognized as a potentially serious drug-drug interaction that can lead to severe myopathy and rhabdomyolysis 2, 5

Alternative Antifungal Options

• For onychomycosis (toenail fungus), terbinafine is the first-line treatment with highest efficacy for dermatophyte infections and fewer drug interactions 6
• Itraconazole can be considered as a second-line treatment, particularly for Candida infections, though it has its own contraindications in patients with heart failure 7
• For systemic fungal infections, treatment should be selected based on the specific pathogen and infection site, with consideration of potential drug interactions 8

Recommendations for Management

• Temporarily discontinue rosuvastatin during fluconazole therapy if antifungal treatment is absolutely necessary 2, 4
• Consider alternative antifungal agents with lower potential for interaction with rosuvastatin 6, 7
• If fluconazole must be used, monitor the patient closely for symptoms of myopathy (muscle pain, weakness, dark urine) and check creatine kinase levels regularly 2, 4
• For onychomycosis specifically, consider topical antifungal treatments as an alternative when systemic therapy poses risks 8, 6

Special Considerations

• Higher doses of fluconazole (such as 450mg weekly) increase the risk of adverse effects and drug interactions 6, 1
• Elderly patients and those with renal impairment are at increased risk of adverse effects from both fluconazole and rosuvastatin 2, 3
• The combination of rosuvastatin with drugs that increase its blood levels may be particularly deleterious for kidney function 2

Clinical Decision Algorithm

1. Assess the necessity of antifungal therapy and confirm diagnosis with mycological examination 6
2. If treatment is necessary, consider these options in order:
   • Use a topical antifungal agent if appropriate for the infection 8, 6
   • Select terbinafine instead of fluconazole if treating onychomycosis 6
   • If fluconazole is absolutely required:
     • Temporarily discontinue rosuvastatin during treatment 2, 4
     • Resume rosuvastatin after completing fluconazole therapy 2
3. Monitor for adverse effects if any statin must be continued with antifungal therapy:
   • Check baseline liver function and creatine kinase 2
   • Monitor for symptoms of myopathy throughout treatment 2, 4
   • Consider dose reduction of rosuvastatin if interaction cannot be avoided 2