What is the treatment regimen for onychomycosis using Fluconazole (fluconazole)?

From the Guidelines

Fluconazole is a viable treatment option for onychomycosis, particularly for patients who cannot tolerate or have contraindications to terbinafine or itraconazole, with a recommended regimen of 450 mg once weekly for at least 6 months in toenail infections and 3 months in fingernail infections. The treatment duration depends on the severity of the infection and the rate of nail growth, with the goal of continuing treatment until the infected nail has completely grown out and been replaced by healthy nail 1. Fluconazole has been shown to have some activity against dermatophytes and some Candida species, although its effectiveness is generally lower than that of terbinafine and itraconazole 1.

Key Considerations

• The dose of fluconazole needs to be adjusted depending on the creatinine clearance, as it is excreted predominantly in the urine 1.
• Higher doses (450 mg per week) and longer treatment durations (9 and 12 months) have been associated with higher cure rates 1.
• Common adverse effects of fluconazole include headache, skin rash, gastrointestinal complaints, and insomnia, with adverse effects leading to treatment discontinuation occurring in up to 58% of patients receiving higher weekly doses (300-450 mg) 1.
• Fluconazole is a weaker inhibitor of the cytochrome P450 enzymes than itraconazole, which may result in fewer drug interactions 1.

Monitoring and Follow-up

• Patients should be monitored for potential side effects, including elevated liver enzymes, gastrointestinal disturbances, and drug interactions, particularly with medications metabolized by the CYP450 enzyme system 1.
• Baseline liver function tests and a complete full blood count are recommended, with monitoring of liver function tests in high-dose or prolonged therapy and in those at risk due to concomitant hepatotoxic drug use 1.

Treatment Outcomes

• Complete cure rates with fluconazole range from 40-60%, which is somewhat lower than terbinafine but still makes it a valuable alternative, especially for dermatophyte infections 1.
• Patients should be advised that visible improvement may take several months as healthy nail grows in 1.

From the Research

Treatment Regimen for Onychomycosis using Fluconazole

• The optimal dosing regimen for fluconazole in the treatment of onychomycosis has been studied, and it is recommended to use the lowest dose of 150 mg weekly for more than 6 months 2.
• Clinical studies have shown that longer treatments, but not higher weekly fluconazole doses, result in better cure rates for toenail, and possibly fingernail, onychomycosis 2.
• A study comparing the efficacy and safety of three different doses of fluconazole (150,300, and 450 mg) given orally once weekly found that all three doses were clinically and mycologically effective, as well as safe and well tolerated 3.
• The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes, with doses between 150 to 450 mg weekly for 6 months being effective 3.
• Another study found that intermittent fluconazole dosing, taken once weekly or on alternate days, is a well-tolerated and efficacious method to treat onychomycosis 4.
• A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis found that fluconazole is effective against dermatophytes, and the preferred regimen is once weekly treatment until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months 5.
• An evidence-based review of oral therapy for onychomycosis found that fluconazole, itraconazole, and terbinafine are effective in the treatment of onychomycosis and have a good safety profile, with terbinafine producing the best results for dermatophyte onychomycosis 6.

Dosage and Duration

• The recommended dose of fluconazole for onychomycosis is 150 mg weekly 2, 5.
• The duration of treatment with fluconazole can vary, but it is typically recommended to continue treatment until the abnormal-appearing nail plate has grown out, which can take 9 to 18 months 5.
• Some studies have found that longer treatments, such as 6 months or more, result in better cure rates for toenail onychomycosis 2, 3.