What are the considerations for using Zetia (ezetimibe) in a patient with impaired renal function (GFR 49)?

From the Guidelines

Ezetimibe (Zetia) can be safely used in patients with impaired renal function, including those with a GFR of 49 ml/min, without dose adjustment. The standard dose of 10 mg once daily can be maintained in this patient population. This is because ezetimibe undergoes extensive glucuronidation in the intestinal wall and liver, with primarily biliary and fecal elimination rather than renal excretion. Only a small portion (less than 20%) of the drug is eliminated through the kidneys. Clinical studies have shown no significant differences in ezetimibe pharmacokinetics in patients with mild, moderate, or severe renal impairment compared to those with normal renal function, as seen in the SHARP trial 1. Monitoring for side effects should follow standard protocols, with attention to muscle symptoms if the patient is also taking statins, as the combination can increase the risk of myopathy. However, this risk is not specifically heightened by renal impairment. Laboratory monitoring should include baseline lipid levels to assess efficacy, but no special renal function monitoring is required specifically for ezetimibe therapy. Key considerations for using ezetimibe in patients with impaired renal function include:

• The drug's mechanism of action, which inhibits NPC1L1 protein and reduces cholesterol absorption in the small intestine 1
• The potential for increased risk of myopathy when used in combination with statins, particularly in patients with reduced kidney function 1
• The lack of significant differences in ezetimibe pharmacokinetics in patients with mild, moderate, or severe renal impairment compared to those with normal renal function 1
• The importance of monitoring for side effects and adjusting treatment as needed to minimize risks and maximize benefits. Overall, the use of ezetimibe in patients with impaired renal function is supported by the available evidence, and the standard dose of 10 mg once daily can be maintained in this patient population.

From the FDA Drug Label

After a single 10-mg dose of ezetimibe in patients with severe renal disease (n=8; mean CrCl ≤30 mL/min/1.73 m2), the mean AUC values for total ezetimibe, ezetimibe-glucuronide, and ezetimibe were increased approximately 1.5-fold, compared to healthy subjects (n=9).

The patient's GFR is 49, which indicates mild to moderate renal impairment. However, the drug label only provides information on patients with severe renal disease (CrCl ≤30 mL/min/1.73 m2). No conclusion can be drawn about the safety of using Zetia (ezetimibe) in a patient with a GFR of 49, as the FDA label does not explicitly address this specific level of renal impairment 2.

From the Research

Considerations for Using Zetia in Patients with Impaired Renal Function

• The patient's GFR is 49, indicating impaired renal function, and the safety of using Zetia (ezetimibe) in this context needs to be evaluated.
• Studies have shown that ezetimibe can be safely administered to patients with chronic kidney disease (CKD) 3, 4.
• Ezetimibe has been found to have renal and vascular protective effects in patients with CKD, including reducing proteinuria and improving endothelial function 3, 4.
• In patients with CKD, ezetimibe has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels and improve lipid profiles without significant changes in renal function 5, 4.
• The combination of ezetimibe and statin therapy has been found to be effective and safe in treating dyslipidemia in patients with CKD and kidney transplant recipients 5, 6.

Key Findings

• A study published in the Journal of Cardiology Cases found that ezetimibe monotherapy improved lipid profiles and reduced proteinuria in a patient with CKD and statin-intolerant dyslipidemia 3.
• A study published in Transplantation Proceedings found that the combination of ezetimibe and statin therapy resulted in significant reductions in total cholesterol, LDL-C, and triglycerides in renal transplant patients with uncontrolled hypercholesterolemia 5.
• A study published in Internal Medicine found that ezetimibe decreased LDL-C levels and improved lipid profiles in patients with CKD, without significant changes in renal function 4.

Safety and Efficacy

• The studies suggest that ezetimibe is safe and effective in patients with impaired renal function, including those with CKD and kidney transplant recipients 3, 5, 4, 6.
• However, it is essential to monitor renal function and adjust the dose of ezetimibe as needed to minimize potential adverse effects.
• The patient's GFR of 49 indicates moderate kidney impairment, and the dose of ezetimibe may need to be adjusted accordingly, although the provided studies do not specifically address dosing adjustments for ezetimibe in patients with impaired renal function, a study on warfarin dosing in patients with impaired kidney function found that moderate kidney impairment required 9.5% lower doses 7.