Can Ezetimibe Be Given in Acute Kidney Injury?
Yes, ezetimibe can be safely administered to patients with acute kidney injury (AKI) without dose adjustment, as it is primarily metabolized via glucuronidation in the intestine and liver rather than through renal excretion. 1
Pharmacokinetic Safety Profile in Renal Impairment
Ezetimibe demonstrates favorable pharmacokinetics in patients with severe renal dysfunction:
After a single 10-mg dose in patients with severe renal disease (mean CrCl ≤30 mL/min/1.73 m²), the mean AUC values for total ezetimibe increased only approximately 1.5-fold compared to healthy subjects. 1
No dose adjustment is necessary in patients with mild-to-severe renal insufficiency, as the drug undergoes minimal renal elimination. 2
Approximately 78% of the administered dose is excreted in feces (predominantly as ezetimibe), while only 11% appears in urine (mainly as ezetimibe-glucuronide). 1
Clinical Evidence Supporting Use in Kidney Disease
Multiple studies demonstrate both efficacy and safety in patients with compromised renal function:
In hemodialysis patients with end-stage renal failure, ezetimibe 10 mg/day for 12 weeks reduced LDL-cholesterol by 24.9% without any adverse events, musculoskeletal symptoms, or elevations in creatine kinase or liver transaminases. 3
In non-diabetic CKD patients, ezetimibe treatment for 6 months significantly reduced proteinuria and markers of tubular injury (urinary L-FABP and 8-OHdG) while decreasing serum ADMA levels, suggesting potential renoprotective effects. 4
A study of 37 dyslipidemic CKD patients treated with ezetimibe 10 mg/day for 24 weeks showed significant reductions in LDL-cholesterol and proteinuria (urine protein-to-creatinine ratio decreased from 1,107.3 to 732.1 mg/gCre) without any adverse events. 5
Practical Administration Guidelines
When prescribing ezetimibe in AKI patients:
Administer the standard dose of 10 mg once daily without modification, as no dosage adjustment is required regardless of renal function severity. 1, 2
The medication can be given in the morning or evening without regard to food, providing flexibility in administration timing. 2
Avoid coadministration with bile acid sequestrants like cholestyramine, which decrease ezetimibe bioavailability by 55%; if both are needed, separate administration by several hours. 1, 2
Important Caveats
While ezetimibe is safe in AKI, consider these clinical nuances:
In kidney transplant recipients receiving cyclosporine, ezetimibe exposure increases 2.4-fold (240% increase in AUC), though studies show this combination remains safe with careful monitoring of cyclosporine levels. 1, 6
One case report documented a renal transplant patient with severe renal insufficiency (CrCl 13.2 mL/min/1.73 m²) on multiple medications including cyclosporine who demonstrated 12-fold greater exposure to total ezetimibe, warranting heightened vigilance in this specific scenario. 1
Unlike statins, which have shown no mortality benefit in patients on maintenance hemodialysis, ezetimibe's safety profile and lipid-lowering efficacy remain intact in this population. 7, 3
Contrast with Other Cardiovascular Medications in AKI
This favorable profile contrasts sharply with other cardiovascular agents:
ARBs and ACE inhibitors should be avoided or temporarily discontinued during AKI episodes, as they directly affect renal hemodynamics and can worsen kidney function. 8
The decision-making for ezetimibe does not require the complex risk-benefit calculations needed for nephrotoxic agents, as it lacks direct renal toxicity. 9