Terbinafine Use in Chronic Kidney Disease
Terbinafine is contraindicated in patients with severe renal impairment (creatinine clearance ≤50 mL/min) and has not been adequately studied in this population, requiring alternative antifungal therapy. 1
Primary Contraindication in CKD
The FDA drug label explicitly states that terbinafine use "has not been adequately studied" in patients with creatinine clearance ≤50 mL/min, effectively contraindicating its use in moderate-to-severe CKD (stages 3b-5). 1
The British Association of Dermatologists explicitly lists renal impairment as a contraindication for terbinafine, as it is primarily cleared by the kidneys. 2, 3
Terbinafine clearance is decreased by approximately 50% in patients with creatinine clearance ≤50 mL/min, leading to drug accumulation and increased toxicity risk. 1
Pharmacokinetic Concerns
Approximately 70% of administered terbinafine is eliminated renally, making kidney function critical for safe drug clearance. 1
The terminal half-life can extend to 200-400 hours due to tissue accumulation in skin and adipose, which is further prolonged in renal impairment. 1
In patients with renal impairment, terbinafine clearance is significantly decreased, creating risk for severe adverse effects including rhabdomyolysis and acute kidney injury. 3, 4
Documented Risks in CKD
A case report documented severe rhabdomyolysis (creatine kinase >100,000 U/L) and anuric acute kidney injury requiring hemodialysis in a patient taking terbinafine 250 mg daily for only 9 days. 4
The risk of nephrotoxicity and drug-induced harm is substantially elevated in CKD patients due to altered pharmacokinetics and reduced drug clearance. 5, 6
Alternative Treatment Options
For patients with CKD requiring antifungal therapy for onychomycosis, topical treatments are the preferred approach: 2, 3
If systemic therapy is absolutely necessary and hepatic function is normal, itraconazole may be considered as an alternative, though it also requires dose adjustment when creatinine clearance <30 mL/min. 2
Fluconazole requires 50% dose reduction when GFR <45 mL/min and is contraindicated in severe renal impairment. 2
Clinical Decision Algorithm
For patients with CKD and onychomycosis:
Calculate creatinine clearance or eGFR 7
- If CrCl >50 mL/min: Terbinafine may be used with caution and close monitoring
- If CrCl ≤50 mL/min: Terbinafine is contraindicated 1
For CrCl ≤50 mL/min, select alternative therapy: 2, 3
- First choice: Topical therapy (amorolfine or ciclopirox)
- Second choice: Consider itraconazole if hepatic function normal and systemic therapy essential
- Monitor renal function closely with any systemic antifungal
If terbinafine was already initiated, discontinue immediately if: 4
- Patient develops muscle pain, weakness, or dark urine (rhabdomyolysis warning signs)
- Acute decline in renal function occurs
- CrCl falls to ≤50 mL/min during treatment
Critical Monitoring Considerations
Baseline renal function must be documented before initiating any systemic antifungal in CKD patients. 7, 8
Drug dosing errors are common in CKD patients and can cause adverse effects and poor outcomes, requiring careful medication reconciliation. 7, 5
The KDIGO guidelines emphasize that medications requiring renal dose adjustment should be calculated using online or electronic calculators to prevent dosing errors. 2
Common Pitfall to Avoid
Do not assume terbinafine can be dose-adjusted for renal impairment—unlike many medications where dose reduction compensates for reduced clearance, terbinafine is specifically contraindicated rather than recommended for adjusted dosing in patients with CrCl ≤50 mL/min. 3, 1 This distinguishes it from drugs like beta-blockers or macrolides where 50% dose reductions are appropriate in advanced CKD. 2