What are the renal adjustments for Fenofibrate (Fibric acid derivative) in patients with Impaired renal function?

From the Guidelines

Fenofibrate requires dose adjustment in patients with renal impairment, with a recommended starting dose of 48 mg daily for those with mild to moderate renal dysfunction (eGFR 30-80 mL/min/1.73m²) and avoidance in severe renal impairment (eGFR <30 mL/min/1.73m²) due to increased risk of adverse effects 1.

Key Considerations

• The medication's pharmacokinetics are significantly altered in renal dysfunction, with decreased clearance and increased plasma half-life, leading to drug accumulation and increased risk of adverse effects such as myopathy and rhabdomyolysis 1.
• Before initiating therapy, baseline renal function should be assessed, and regular monitoring should continue throughout treatment to ensure safe use and minimize potential harm.
• If a patient on fenofibrate experiences worsening renal function during treatment, dose reduction or discontinuation may be necessary based on clinical judgment and laboratory parameters 1.

Dosing Recommendations

• For patients with mild to moderate renal dysfunction (eGFR 30-80 mL/min/1.73m²), the recommended starting dose is 48 mg daily 1.
• For those with severe renal impairment (eGFR <30 mL/min/1.73m²), fenofibrate is generally not recommended due to increased risk of adverse effects 1.

Monitoring and Safety

• Renal status should be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter, using both serum creatinine level and eGFR based on creatinine 1.
• Fenofibrate should not be used if moderate or severe renal impairment is present, and if eGFR is between 30 and 59 mL/min per 1.73 m², the dose of fenofibrate should not exceed 54 mg/day 1.

From the FDA Drug Label

Renal Impairment The pharmacokinetics of fenofibric acid was examined in patients with mild, moderate, and severe renal impairment. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2) showed 2. 7-fold increase in exposure for fenofibric acid and increased accumulation of fenofibric acid during chronic dosing compared to that of healthy subjects. Patients with mild to moderate renal impairment (eGFR 30 mL/min/1.73m2 to 59 mL/min/1. 73m2) had similar exposure but an increase in the half-life for fenofibric acid compared to that of healthy subjects. Based on these findings, the use of fenofibrate should be avoided in patients who have severe renal impairment and dose reduction is required in patients having mild to moderate renal impairment [see Dosage and Administration (2. 4)].

Fenofibrate dose adjustment for renal impairment:

• Severe renal impairment (eGFR < 30 mL/min/1.73m2): Avoid use of fenofibrate.
• Mild to moderate renal impairment (eGFR 30 mL/min/1.73m2 to 59 mL/min/1.73m2): Initiate treatment with a dose of 54 mg per day and increase only after evaluation of the effects on renal function and lipid levels at this dose 2.

From the Research

Fenofibrate Renal Adjustment

• Fenofibrate has been shown to be beneficial in patients with type 2 diabetes and moderate renal impairment, with no excess drug-related safety concerns compared to those with no or mild renal impairment 3.
• The use of fenofibrate may be associated with an increase in serum creatinine levels, but this effect is often transient and reversible, even without treatment discontinuation 4.
• Studies have suggested that fenofibrate may not be nephrotoxic, but close monitoring of serum creatinine levels is still relevant, especially in high-risk patients 4, 5.
• Fenofibrate treatment has been shown to result in increased serum creatinine levels and reduced estimated glomerular filtration rates in a primary care setting, highlighting the need for regular renal function monitoring 5.
• In patients with advanced chronic kidney disease, fenofibrate has been shown to delay the need for dialysis and reduce cardiovascular risk, with potential benefits when combined with high-intensity statins 6.
• The efficacy and safety of fenofibrate in patients with chronic kidney disease have been compared to other treatments, such as pemafibrate, which may be a safer alternative with equivalent efficacy 7.

Key Considerations

• Patients with moderate renal impairment may benefit from fenofibrate treatment, but require close monitoring of serum creatinine levels 3, 4.
• Fenofibrate-associated increases in serum creatinine levels may be transient and reversible, but regular monitoring is still necessary 4, 5.
• The combination of fenofibrate and high-intensity statins may have additional benefits in patients with advanced chronic kidney disease 6.
• Alternative treatments, such as pemafibrate, may be considered in patients with chronic kidney disease, especially those at high risk of renal dysfunction 7.