Terbinafine Use in Chronic Kidney Disease
Terbinafine can be used in patients with chronic kidney disease (CKD), but dose adjustment is not required for mild to moderate renal impairment, while its use in severe renal impairment (CKD stages 4-5) has not been adequately studied and should be approached with caution.
Pharmacokinetics in CKD
Terbinafine's pharmacokinetic profile in renal impairment is characterized by:
- According to the FDA label, terbinafine clearance is decreased by approximately 50% in patients with renal impairment (creatinine clearance ≤ 50 mL/min) compared to normal volunteers 1
- The FDA specifically notes that "in patients with renal impairment (creatinine clearance less than or equal to 50 mL/min) the use of terbinafine tablets has not been adequately studied" 1
- Terbinafine is extensively metabolized by at least seven CYP isoenzymes with major contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19 1
- Approximately 70% of the administered dose is eliminated in the urine 1
Recommendations for Use in CKD
Dosing Considerations
- For patients with mild to moderate renal impairment (CKD stages 1-3), standard dosing of terbinafine (250 mg daily) can generally be used
- For patients with severe renal impairment (CKD stages 4-5), consider:
- Using the lowest effective dose
- Monitoring more frequently for adverse effects
- Considering alternative antifungal agents if appropriate
Monitoring Requirements
Before initiating terbinafine in CKD patients:
- Baseline liver function tests
- Complete blood count
- Assessment of renal function (eGFR)
During treatment:
- Monitor liver function tests at weeks 1,2, and 4 after starting therapy, then every 3 months 2
- Monitor for signs of rhabdomyolysis, which has been reported as a rare but serious adverse effect that can worsen kidney function 3, 4
- Monitor kidney function regularly, especially in patients with pre-existing CKD
Special Considerations
Potential Risks
- Rare cases of rhabdomyolysis associated with terbinafine have been reported, which could potentially worsen kidney function in CKD patients 3
- Exercise-induced rhabdomyolysis has been reported in patients taking terbinafine, suggesting caution regarding intense physical activity while on this medication 4
Evidence in Transplant Recipients
- A study in kidney transplant recipients showed that terbinafine could be used with acceptable tolerance profiles, even in patients on tacrolimus-based antirejection therapy 5
- This suggests that terbinafine may be a viable option for treating severe onychomycosis in patients with compromised renal function
Practice Points
Follow the KDOQI guideline practice point 4.2.1: "Consider GFR when dosing medications cleared by the kidneys" 6
Apply practice point 4.2.2: "For most people and clinical settings, validated eGFR equations using serum creatinine are appropriate for drug dosing" 6
Consider practice point 4.3.1.2: "Establish collaborative relationships with other healthcare providers and pharmacists and/or use tools to ensure and improve drug stewardship in people with CKD to enhance management of their complex medication regimens" 6
Monitor for potential drug interactions, especially if the patient is on multiple medications, as is common in CKD
Conclusion
While terbinafine can be used in CKD patients, careful consideration of the degree of renal impairment, vigilant monitoring, and awareness of potential adverse effects are essential. For patients with severe renal impairment (CKD stages 4-5), the benefit-risk ratio should be carefully evaluated, and alternative antifungal treatments may be considered if appropriate.