What is the difference between Flucanazole and Terbinafine for treating fungal infections?

Fluconazole vs Terbinafine for Fungal Infections

Direct Comparison

Terbinafine is significantly superior to fluconazole for dermatophyte infections (nail and skin fungus), while fluconazole is the preferred agent for Candida (yeast) infections. The choice between these agents depends entirely on the causative organism rather than being interchangeable options.

Onychomycosis (Nail Fungus)

For Dermatophyte Infections

• Terbinafine 250 mg daily for 12 weeks is first-line therapy and achieves mycological cure rates of 89% compared to only 49-51% with fluconazole 1
• Complete clinical cure at 60 weeks: 67% with terbinafine vs 21-32% with fluconazole 1
• Terbinafine demonstrates significantly lower relapse rates (21-23%) compared to itraconazole (48-53%) for dermatophyte onychomycosis 2

For Candida Nail Infections

• Itraconazole is first-line for Candida onychomycosis, with cure rates of 92% compared to only 40% with terbinafine 2
• Fluconazole 450 mg once weekly for at least 6 months is an alternative when itraconazole cannot be used 3
• Fluconazole achieves mycological cure rates of 47-62% for toenail infections, but clinical cure rates are lower at 28-36% 3

Vulvovaginal Candidiasis

Fluconazole 150 mg as a single oral dose is the treatment of choice, achieving clinical cure rates of 66.6% and mycological cure rates of 66.6% 4. Terbinafine is significantly inferior for this indication, with only 33.3% clinical and mycological cure rates 4.

Tinea Capitis (Scalp Ringworm)

• Terbinafine is first-line for Trichophyton infections 5
• Griseofulvin is preferred for Microsporum species 5
• Fluconazole is reserved as an alternative agent for refractory cases only 5
• Fluconazole has demonstrated efficacy against T. violaceum, T. verrucosum, and M. canis, but cost and limited availability make it second-line 5

Systemic Candida Infections

Fluconazole is the preferred azole for most Candida infections in non-neutropenic patients 5, 6. Key considerations:

• Fluconazole exhibits predictable pharmacokinetics and high oral bioavailability 7
• Well-tolerated in most patients including children, elderly, and immunocompromised 6
• For C. glabrata: Consider echinocandins or amphotericin B first-line due to potential resistance; fluconazole only if isolate is susceptible 5
• For C. krusei: Fluconazole is ineffective; use echinocandins or amphotericin B 5

Mechanism and Spectrum Differences

Terbinafine (Allylamine)

• Inhibits squalene epoxidase in fungal cell membrane synthesis 8
• Highly effective against dermatophytes (skin, nail, hair fungi) 8
• Poor activity against Candida species 4

Fluconazole (First-Generation Triazole)

• Inhibits fungal cytochrome P450 enzymes 8
• Excellent activity against most Candida species and Cryptococcus 6, 7
• Limited activity against molds (no Aspergillus coverage) 8
• Weaker cytochrome P450 inhibitor than itraconazole, resulting in fewer drug interactions 3

Safety and Monitoring

Fluconazole

• Common adverse effects: headache, skin rash, gastrointestinal complaints, insomnia 3
• Dose adjustment required for renal impairment (primarily renally excreted) 3
• Monitor liver function tests with higher doses or pre-existing liver disease 3
• Discontinuation rates: 20% at 150 mg weekly, increasing to 58% at 300-450 mg doses 3

Terbinafine

• Generally well-tolerated with low adverse event incidence 1
• Baseline liver function tests recommended 2
• Contraindicated in patients with history of hepatotoxicity 2

Clinical Algorithm

Step 1: Confirm diagnosis with mycological examination (culture or microscopy) 3

Step 2: Identify causative organism

• Dermatophyte (Trichophyton, Epidermophyton, Microsporum) → Terbinafine first-line 2, 1
• Candida species → Fluconazole or itraconazole first-line 2, 6

Step 3: Site-specific treatment

• Onychomycosis (dermatophyte): Terbinafine 250 mg daily × 12 weeks 2, 1
• Onychomycosis (Candida): Itraconazole 200 mg daily × 12 weeks or pulse therapy 2
• Vulvovaginal candidiasis: Fluconazole 150 mg single dose 4
• Systemic candidiasis: Fluconazole 400-800 mg daily (after loading dose) 5

Critical Pitfalls to Avoid

• Never use terbinafine for Candida infections—it has minimal efficacy against yeasts 4
• Never use fluconazole empirically for nail infections without confirming the organism—it will fail in 50-70% of dermatophyte cases 1
• Do not use fluconazole if the patient has been on azole prophylaxis—resistance is likely 5
• Always treat concurrent tinea pedis when treating toenail onychomycosis to prevent reinfection 3