Effect of Finasteride on Kidney Function in Patients with Impaired Renal Function
No dosage adjustment of finasteride is necessary in patients with renal impairment, as the drug has been well tolerated in patients with chronic renal impairment with creatinine clearances ranging from 9.0 to 55 mL/min. 1
Pharmacokinetics in Renal Impairment
Finasteride's pharmacokinetic profile in patients with renal impairment shows:
- AUC, maximum plasma concentration, half-life, and protein binding after a single dose are similar to values obtained in healthy volunteers 1
- Urinary excretion of metabolites decreases in patients with renal impairment, with a compensatory increase in fecal excretion 1
- Plasma concentrations of metabolites are significantly higher in patients with renal impairment (approximately 60% increase in total radioactivity AUC) 1
- Despite higher metabolite concentrations, finasteride has been well tolerated in BPH patients with normal renal function receiving up to 80 mg/day for 12 weeks, where exposure to metabolites would presumably be much greater 1
Metabolism and Excretion Pathway
Finasteride undergoes extensive hepatic metabolism via the cytochrome P450 3A4 enzyme subfamily, with:
- Mean plasma clearance of 165 mL/min in healthy subjects 1
- Mean elimination half-life of 6 hours (range 3-16 hours) 1
- Approximately 39% of the dose excreted in urine as metabolites 1
- Approximately 57% excreted in feces 1
Potential Concerns in Renal Impairment
Despite the FDA label indicating no dosage adjustment is necessary, some research raises potential concerns:
- Animal studies suggest finasteride-induced hormonal imbalance may impair kidney morphology and physiology 2
- Finasteride inhibits 5α-reductase type 2, affecting androgen homeostasis, which could potentially impact renal function 2
- Some researchers have suggested that long-term use of finasteride may be associated with potential kidney dysfunction 3
Clinical Implications
When using finasteride in patients with impaired renal function:
- Monitor kidney function periodically, especially in patients with severe renal impairment
- Be aware that while the parent drug pharmacokinetics remain unchanged, metabolite concentrations will be higher
- Consider that the clinical significance of higher metabolite concentrations appears minimal based on tolerability data 1
- For patients with both BPH and impaired renal function, the benefits of finasteride in reducing prostate volume and improving urinary symptoms likely outweigh potential risks
Conclusion
The FDA-approved labeling clearly states that no dosage adjustment is necessary for finasteride in patients with renal impairment 1. While some preclinical research suggests potential concerns about long-term effects on kidney function, the clinical evidence supports the safety of finasteride in patients with impaired renal function at standard doses.