What is the first-line treatment regimen for onychomycosis (fungal infection of the nails) involving both toenails and fingernails?

First-Line Treatment for Onychomycosis Involving Both Fingernails and Toenails

Oral terbinafine 250 mg daily is the first-line treatment: 6 weeks for fingernails and 12 weeks for toenails, taken concurrently when both are infected. 1, 2

Treatment Regimen

For simultaneous fingernail and toenail involvement, treat with terbinafine 250 mg once daily for 12 weeks (the longer duration required for toenails will adequately cover the fingernail treatment period). 1, 3

• Re-evaluate patients 3-6 months after treatment initiation and provide additional treatment if disease persists. 1, 3
• The fingernails will typically achieve mycological cure by 12.5 weeks and clinical cure by 20.5 weeks. 4
• Toenails require longer, achieving mycological cure by 24 weeks and clinical cure by 44 weeks. 4

Why Terbinafine is First-Line

• Terbinafine demonstrates superior efficacy compared to itraconazole, with complete cure rates of 55% versus 26% at 72 weeks, and long-term mycological cure without retreatment of 46% versus 13% at 5 years. 1
• Terbinafine is fungicidal against dermatophytes with very low minimum inhibitory concentrations, making it more effective than the fungistatic azoles. 3
• Terbinafine has minimal drug-drug interactions compared to azole antifungals, with only cytochrome P450 2D6 substrates requiring caution. 1, 3, 5

Pre-Treatment Requirements

• Confirm diagnosis with laboratory testing (KOH preparation, fungal culture, or nail biopsy) before initiating treatment. 2, 6
• Obtain baseline liver function tests (LFTs) and complete blood count (CBC) before starting therapy. 3, 5

Monitoring During Treatment

• More vigilant LFT monitoring is required for high-risk patients: those with pre-existing liver disease, concomitant hepatotoxic medications, continuous therapy exceeding one month, or history of heavy alcohol consumption. 3, 5
• Monitor for hepatotoxicity and discontinue terbinafine if liver injury develops. 2
• If neutrophil count drops to ≤1,000 cells/mm³, discontinue terbinafine immediately. 2

Absolute Contraindications

• Active or chronic liver disease 3, 5
• History of allergic reaction to oral terbinafine 3, 2
• Renal impairment with creatinine clearance ≤50 mL/min 5
• Lupus erythematosus 3

Second-Line Alternative

If terbinafine is contraindicated or not tolerated, use itraconazole 200 mg daily for 12 weeks continuously, or pulse therapy at 400 mg daily for 1 week per month (2 pulses for fingernails, 3 pulses for toenails). 1

• Itraconazole is less effective than terbinafine but remains superior to fluconazole and griseofulvin. 1
• Itraconazole has more significant drug interactions due to cytochrome P450 inhibition and is contraindicated in congestive heart failure. 1

Third-Line Alternative

Fluconazole 450 mg once weekly can be used when both terbinafine and itraconazole cannot be tolerated: 3 months for fingernails and at least 6 months for toenails. 1, 7

• Fluconazole has lower efficacy (mycological cure 47-62% for toenails, 89-100% for fingernails) but offers convenient once-weekly dosing. 1, 7
• Requires dose adjustment in renal impairment (50% reduction when GFR <45 mL/min). 5, 7

Critical Warnings

• Permanent taste disturbance is a rare but serious adverse effect—warn all patients and discontinue if it occurs. 1, 5, 2
• Severe cutaneous reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome have been reported—discontinue immediately if signs develop. 5, 2
• Liver failure leading to transplant or death has occurred with oral terbinafine—maintain vigilance for hepatotoxicity. 2

Special Populations

• Diabetic patients: Terbinafine is preferred due to low risk of drug interactions and hypoglycemia, and because itraconazole is contraindicated in heart failure (more prevalent in diabetics). 1
• Immunosuppressed patients: Terbinafine is preferred over itraconazole due to fewer interactions with antiretrovirals and immunosuppressive medications. 1
• Pediatric patients: Terbinafine dosing is weight-based (6.25 mg/day if <20 kg, 125 mg/day for 20-40 kg, 250 mg/day if >40 kg) for 6 weeks (fingernails) or 12 weeks (toenails). 1