What are alternative antifungal medications for patients who cannot take terbinafine (Lamisil) due to interactions with rifampin (Rifadin)?

Alternative Antifungal Options When Terbinafine Cannot Be Used with Rifampin

Griseofulvin is the preferred alternative for dermatophyte infections when terbinafine must be avoided due to rifampin co-administration, as rifampin significantly reduces terbinafine plasma concentrations, rendering it ineffective. 1

Understanding the Drug Interaction

• Rifampin is a potent inducer of hepatic microsomal enzymes (CYP450 system), which dramatically reduces plasma concentrations of terbinafine and most azole antifungals to subtherapeutic levels. 1
• Terbinafine plasma concentrations are specifically reduced by rifampin, making it ineffective for treating fungal infections during concurrent use. 1
• Itraconazole, ketoconazole, and voriconazole concentrations may also become subtherapeutic with any rifamycin co-administration. 1

First-Line Alternative: Griseofulvin

Griseofulvin should be your primary choice as it has no significant interaction with rifampin and maintains therapeutic efficacy. 1

Dosing and Duration

• Adults: 500 mg to 1 g daily (though 1 g is most commonly prescribed for optimal efficacy). 1
• Children: 20 mg/kg/day for tinea capitis, administered for 6-18 weeks depending on the causative organism. 1, 2
• For Trichophyton species: May require higher doses (up to 25 mg/kg daily) for prolonged periods (12-18 weeks) due to reduced clinical efficacy compared to Microsporum species. 1
• For Microsporum species: Griseofulvin is more effective than terbinafine, with 8 weeks showing superior outcomes. 1

Key Advantages

• Licensed for use in both adults and children in the U.K. 1
• Extensive clinical experience with well-established safety profile. 1
• No interaction with rifampin (only decreased by rifampicin in the context of other drugs, but griseofulvin itself is not significantly affected). 1
• Available in suspension form for children, allowing accurate dosage adjustments. 1

Important Limitations

• Requires prolonged treatment duration (6-18 weeks), which may affect compliance. 1
• Lower cure rates compared to terbinafine for Trichophyton infections (57% vs 87% for itraconazole). 3
• Contraindicated in lupus erythematosus, porphyria, and severe liver disease. 1
• Side effects include nausea and rashes in 8-15% of patients. 1

Second-Line Alternative: Fluconazole

Fluconazole can be used with dose adjustment, as it is less affected by rifampin than other azoles, though monitoring is essential. 1

Dosing Considerations

• Standard dosing for tinea: 6 mg/kg/day for 2-3 weeks in children. 2
• The dose of fluconazole may need to be increased when co-administered with rifampin to maintain therapeutic levels. 1
• Once-weekly dosing regimens have been used and appear well tolerated. 1

Efficacy Profile

• Effective against Trichophyton violaceum, T. verrucosum, and Microsporum canis with 84-86% cure rates. 1, 2
• Comparable efficacy to griseofulvin in multicentre studies of mixed pathogens. 1

Critical Caveats

• Not licensed for tinea treatment in children aged <10 years in the U.K., though licensed for mucosal candidiasis in all children. 1
• Licensed for tinea in children >1 year in Germany, providing some regulatory precedent. 1
• Requires dose increase when used with rifampin, and therapeutic drug monitoring may be beneficial. 1

Agents to Avoid

Itraconazole

• Explicitly contraindicated with rifampin due to decreased efficacy from concomitant use. 1
• Rifampin dramatically reduces itraconazole concentrations to subtherapeutic levels. 1
• Drug interaction is bidirectional and clinically significant. 1

Voriconazole

• Should not be used with rifampin as concentrations become subtherapeutic. 1
• More potent than griseofulvin or fluconazole against dermatophytes, but cost, licensing restrictions, and rifampin interaction limit usage. 1

Ketoconazole

• Withdrawn from use in U.K. and Europe in 2013 due to hepatotoxicity risk. 1
• Not a viable option regardless of drug interactions. 1

Clinical Monitoring Strategy

• The endpoint of treatment is mycological cure, not just clinical improvement—repeat mycology sampling is mandatory until clearance is achieved. 1, 3
• If clinical improvement occurs but mycology remains positive, continue current therapy for an additional 2-4 weeks. 1
• If no initial clinical improvement occurs, proceed to second-line therapy. 1
• Monitor for griseofulvin side effects (gastrointestinal symptoms, rashes) which occur in 8-15% of patients. 1, 2

Organism-Specific Recommendations

For Trichophyton Species

• Griseofulvin 20-25 mg/kg/day for 12-18 weeks is the safest choice during rifampin therapy. 1
• Fluconazole 6 mg/kg/day with dose adjustment is an alternative if griseofulvin fails. 1, 2

For Microsporum Species

• Griseofulvin remains the treatment of choice and is more effective than terbinafine for these organisms. 1
• Standard dosing of 20 mg/kg/day for 8 weeks achieves superior outcomes. 1