Fenofibrate Dosing in Renal Impairment
The minimum dose of fenofibrate for patients with impaired renal function is 54 mg daily for mild to moderate renal impairment (eGFR 30-59 mL/min/1.73m²), and fenofibrate should be avoided completely in patients with severe renal impairment (eGFR <30 mL/min/1.73m²). 1, 2
Dosing Recommendations Based on Renal Function
- For patients with normal renal function or mild renal impairment (eGFR ≥60 mL/min/1.73m²), the standard dose range is 54-160 mg daily 1
- For patients with mild to moderate renal impairment (eGFR 30-59 mL/min/1.73m²), initiate therapy at 54 mg daily and increase only after evaluation of effects on renal function and lipid levels 1, 3
- Fenofibrate is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73m²), including those receiving dialysis 1, 2
Pharmacokinetics in Renal Impairment
- Patients with severe renal impairment show a 2.7-fold increase in exposure to fenofibric acid (the active metabolite) and increased accumulation during chronic dosing 1
- Patients with mild to moderate renal impairment have similar exposure but an increased half-life for fenofibric acid compared to those with normal renal function 1
- Fenofibrate is not dialyzable and has a markedly prolonged half-life in patients with renal failure 4
Monitoring Recommendations
- Evaluate renal status before initiating fenofibrate therapy 2
- Assess renal function within 3 months after initiation and continue monitoring every 6 months thereafter 2
- If eGFR decreases persistently to <30 mL/min/1.73m², fenofibrate should be discontinued 2, 1
- Monitor for adverse effects, particularly elevations in serum creatinine, which can occur with fenofibrate therapy 5
Clinical Considerations
- Despite concerns about renal effects, the FIELD study showed that patients with type 2 diabetes and moderate renal impairment benefited from long-term fenofibrate without excess drug-related safety concerns compared to those with no or mild renal impairment 6
- Consider the benefits of ASCVD risk reduction or triglyceride lowering against potential adverse effects when using fenofibrate in patients with renal impairment 2
- Fenofibrate should be taken with meals to optimize bioavailability 1
Potential Adverse Effects
- Fenofibrate can cause transient or persistent increases in serum creatinine levels 5
- Case reports have documented significant increases in serum creatinine with fenofibrate therapy, particularly at higher doses in patients with pre-existing renal impairment 5
- These elevations are generally reversible upon discontinuation of the medication 5
Alternative Options
- If fenofibrate cannot be used due to severe renal impairment, gemfibrozil may be considered as an alternative fibrate, though at a reduced dose of 600 mg daily (compared to standard 1200 mg daily) 2
- However, gemfibrozil should also be used with caution in patients with serum creatinine >2 mg/dL 3
Remember that renal function should be carefully monitored in all patients receiving fenofibrate, particularly those with pre-existing renal impairment, and the medication should be discontinued if significant deterioration in renal function occurs.