Is ketoconazole (an oral antifungal medication) a suitable treatment option for toenail fungus (onychomycosis)?

Ketoconazole Should Not Be Used for Toenail Fungus

Ketoconazole is explicitly contraindicated for the treatment of onychomycosis (toenail fungus) due to serious hepatotoxicity risks, including fatal outcomes and liver transplantation requirements, and is not licensed for this indication. 1

Why Ketoconazole Is Contraindicated

The FDA drug label explicitly states that ketoconazole tablets are not indicated for treatment of onychomycosis due to serious adverse reactions, including fatal hepatotoxicity. 1 The British Association of Dermatologists guidelines reinforce this, stating that ketoconazole cannot be prescribed for dermatophyte onychomycosis because of problems with hepatotoxicity. 2

Specific Safety Concerns

• Fatal hepatotoxicity has occurred with ketoconazole use, with some cases requiring liver transplantation. 1
• Serious liver injury has been reported in patients with no obvious risk factors for liver disease. 1
• Hepatotoxicity occurred with both high doses for short durations and low doses for long durations. 1
• Cases of hepatitis have been reported in children. 1
• Ketoconazole can cause QT prolongation and life-threatening ventricular dysrhythmias. 1

Limited Exception: Recalcitrant Candida Infections Only

Ketoconazole may be considered only for some recalcitrant cases of yeast (Candida) infection affecting the nails, but this is not for typical dermatophyte toenail fungus. 2 Even in this narrow scenario, it should only be used when other effective antifungal therapy is not available or tolerated. 1

First-Line Treatment: Terbinafine

Terbinafine 250 mg daily for 12 weeks is the first-line treatment for toenail onychomycosis caused by dermatophytes. 3, 4 This recommendation is based on:

• Superior efficacy: Cure rates well over 80% for toenail infections. 5
• Lower relapse rates compared to other antifungals. 3, 4
• Fungicidal activity against dermatophytes with very low minimum inhibitory concentrations. 3
• Minimal drug interactions compared to azole antifungals. 3
• Strength of recommendation A, level of evidence 1+. 3

Pre-Treatment Requirements for Terbinafine

• Obtain baseline liver function tests and complete blood count before starting treatment. 3, 4
• Contraindicated in patients with active or chronic liver disease or lupus erythematosus. 3

Alternative Systemic Options (If Terbinafine Contraindicated)

Itraconazole

• Pulse therapy: 400 mg daily for 1 week per month, with 3 pulses for toenails. 2
• Active against both dermatophytes and Candida species. 2
• Less effective than terbinafine for dermatophyte onychomycosis. 2
• Requires liver function monitoring for treatment durations longer than 1 month. 2

Fluconazole

• Not licensed for onychomycosis in many jurisdictions. 2
• Can be considered as second-line: 3-6 mg/kg once weekly for 18-26 weeks for toenails. 2, 4
• Dose and duration not yet clearly established. 2

Griseofulvin

• Poor cure rates and high relapse rates for toenail infections. 2
• Lengthy treatment necessary (often 12-18 months for toenails). 2
• Only recommended when newer agents are contraindicated. 2

Common Pitfall to Avoid

Do not prescribe ketoconazole for typical toenail fungus (dermatophyte onychomycosis). Despite older literature from the 1980s-1990s showing some efficacy 6, 7, the hepatotoxicity risk has led to explicit contraindication by regulatory authorities and professional guidelines. 1, 2 The availability of safer, more effective alternatives (terbinafine, itraconazole) makes ketoconazole use unjustifiable for this indication. 5, 8, 9