What is the recommended oral dosage of terbinafine (antifungal medication) for an adult patient with a fungal infection, particularly for onychomycosis, and how does it vary with impaired renal function?

Oral Terbinafine Dosing for Onychomycosis

The standard adult dose of oral terbinafine is 250 mg once daily: 6 weeks for fingernail onychomycosis and 12 weeks for toenail onychomycosis. 1, 2

Standard Adult Dosing by Site of Infection

• Toenail onychomycosis: 250 mg once daily for 12 weeks (up to 16 weeks for severe cases) 1, 3, 2
• Fingernail onychomycosis: 250 mg once daily for 6 weeks 1, 2
• Tinea pedis (foot fungus): 250 mg once daily for 1-2 weeks 4

The British Association of Dermatologists designates this as a strength of recommendation A with level of evidence 1+. 1

Administration Details

• Terbinafine can be taken with or without food, as absorption is not significantly affected by food intake (AUC increases <20% with food). 1, 2
• The optimal clinical effect appears months after treatment completion due to the time required for healthy nail outgrowth. 2
• Terbinafine persists in the nail for up to 6 months after treatment cessation due to its lipophilic properties and long half-life, allowing continued fungicidal activity. 1, 3

Dosing in Renal Impairment

Terbinafine has not been adequately studied in patients with creatinine clearance ≤50 mL/min, and the FDA label does not provide specific dosing recommendations for this population. 2

• In patients with renal impairment (CrCl ≤50 mL/min), terbinafine clearance decreases by approximately 50% compared to normal volunteers. 2
• Exercise caution and consider alternative antifungals or close monitoring if terbinafine must be used in severe renal impairment. 2

Pre-Treatment Requirements

Baseline liver function tests (ALT and AST) and complete blood count are mandatory before initiating terbinafine. 1, 3, 2

• Mycological confirmation through KOH preparation, fungal culture, or nail biopsy is required before prescribing, as treating without confirmation is the most common cause of treatment failure. 3
• Terbinafine is contraindicated in patients with active or chronic liver disease. 1, 2

Monitoring During Treatment

• Patients with pre-existing liver abnormalities, history of hepatitis, or heavy alcohol use require liver function monitoring throughout treatment. 1, 4
• If neutrophil count drops to ≤1,000 cells/mm³, terbinafine must be discontinued. 2

Critical Safety Warnings

Instruct patients to immediately discontinue terbinafine and contact their physician if they develop: 2

• Persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools (hepatotoxicity warning)
• Taste or smell disturbances (may be severe, prolonged, or permanent)
• Hives, mouth sores, blistering/peeling skin, facial swelling, difficulty swallowing or breathing (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• New or worsening lupus symptoms (erythema, scaling, photosensitivity)

Alternative Dosing Regimens

While the FDA-approved continuous daily regimen remains standard, pulse therapy has been studied: 5, 6

• Pulse regimen: 500 mg daily for 7 days per month for 4 months showed comparable efficacy to continuous dosing in some studies. 6
• Quarterly pulse regimen: 500 mg daily for 7 days every 3 months (four total treatments) demonstrated effectiveness in dermatophyte onychomycosis. 5

However, these pulse regimens are not FDA-approved, and the standard continuous daily dosing should be used in routine practice. 2

Treatment Failure Management

• Re-evaluate patients 3-6 months after treatment initiation. 1, 3
• If disease persists, confirm dermatophyte infection through repeat culture and restart terbinafine immediately without additional waiting period. 1, 3
• Consider itraconazole (200 mg daily for 12 weeks or 400 mg daily for 1 week per month for 3 cycles) only after second terbinafine failure. 1

Drug Interactions

Terbinafine has minimal drug-drug interactions compared to azole antifungals, making it safer for patients on multiple medications. 1, 3

• The primary interaction involves drugs metabolized by cytochrome P450 2D6 (certain antidepressants, beta-blockers, antiarrhythmics). 1
• Rifampin increases terbinafine clearance by 100%; cimetidine decreases it by 33%. 2
• Fluconazole increases terbinafine exposure (52% increase in Cmax, 69% increase in AUC). 2