Fenofibrate Dosing in Impaired Renal Function
Fenofibrate should not be used in patients with severe renal impairment (eGFR <30 mL/min/1.73m²), and the dose should not exceed 54 mg/day in patients with moderate renal impairment (eGFR 30-59 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): Standard dose of 96 mg daily 1
- For patients with moderate renal impairment (eGFR 30-59 mL/min/1.73m²): Reduced dose of 48 mg daily (or maximum 54 mg daily depending on formulation) 1
- For patients with severe renal impairment (eGFR <30 mL/min/1.73m²): Avoid use 1, 2
- For kidney transplant recipients: Avoid use 1
Pharmacokinetic Considerations
- Fenofibrate is a prodrug that is rapidly hydrolyzed to the active metabolite fenofibric acid 2, 3
- Patients with severe renal impairment (eGFR <30 mL/min/1.73m²) show a 2.7-fold increase in exposure to fenofibric acid and increased accumulation during chronic dosing 2
- Patients with mild to moderate renal impairment (eGFR 30-59 mL/min/1.73m²) have similar exposure but increased half-life of fenofibric acid compared to those with normal renal function 2
- Approximately 60% of fenofibrate is excreted in urine, primarily as fenofibric acid and its glucuronate conjugate 2, 4
Monitoring Recommendations
- Renal status should be evaluated before initiating fenofibrate therapy 1
- Assess renal function within 3 months after initiation 1
- Continue monitoring renal function every 6 months thereafter 1
- Use both serum creatinine level and eGFR based on creatinine for monitoring 1
- If eGFR decreases persistently to <30 mL/min/1.73m², fenofibrate should be discontinued 1
Important Clinical Considerations
- Fenofibrate may cause a reversible increase in serum creatinine levels that does not reflect actual impairment of renal function but rather increased metabolic production of creatinine 5
- When considering fenofibrate in patients with renal impairment, assess the benefits of ASCVD risk reduction or triglyceride lowering against potential adverse effects 1
- Gemfibrozil may be an alternative fibrate option in patients with severe renal impairment, with a reduced dose of 600 mg daily (compared to standard 1200 mg daily) 1
- Fenofibrate should not be initiated in patients on statin therapy due to increased risk of muscle symptoms and rhabdomyolysis; if combination therapy is necessary, use with low or moderate-intensity statins only 1
Formulation Considerations
- Different fenofibrate formulations have varying bioavailability 4, 3
- The 54 mg and 160 mg tablets of the suprabioavailable formulation are equivalent to 67 mg and 200 mg micronized capsules, respectively 4
- The 105 mg fenofibric acid tablet is bioequivalent to the 145 mg fenofibrate tablet 3
- Always consult the manufacturer's prescribing information as there are several forms of fenofibrate available 1
By carefully adjusting fenofibrate dosing based on renal function and monitoring kidney parameters regularly, clinicians can optimize the risk-benefit profile in patients with impaired renal function while minimizing potential adverse effects.