Ezetimibe Dosing in Chronic Kidney Disease by eGFR

No dose adjustment of ezetimibe is required regardless of eGFR level, including in patients with severe renal impairment. 1

Pharmacokinetic Evidence Supporting No Dose Adjustment

After a single 10 mg dose in patients with severe renal disease (CrCl ≤30 mL/min/1.73 m²), mean AUC values for total ezetimibe increased approximately 1.5-fold compared to healthy subjects, but this increase is not clinically significant and does not warrant dose modification 1
The FDA drug label explicitly states: "No dosage adjustment of ezetimibe tablets is necessary in patients with renal impairment" 1
Ezetimibe is primarily eliminated via fecal excretion (78% of dose), with only 11% excreted renally, making it inherently safe across all levels of kidney function 1, 2

Initiate statin or statin/ezetimibe combination in all patients ≥50 years of age 3, 4

KDIGO provides a Grade 1A recommendation (strongest level) for statin or statin/ezetimibe treatment in adults ≥50 years with eGFR <60 mL/min/1.73 m² who are not on chronic dialysis or kidney transplantation 3, 4
Ezetimibe can be initiated upfront with a statin or added if LDL-C remains elevated on statin monotherapy 4
This recommendation applies to eGFR ranges of 30-59 mL/min/1.73 m² (Stage 3) and 15-29 mL/min/1.73 m² (Stage 4) 3

Initiate statin monotherapy first; reserve ezetimibe as add-on therapy 4

For adults ≥50 years with CKD stages 1-2, KDIGO recommends statin monotherapy (Grade 1B) 4
Ezetimibe should be added only if LDL-C targets are not achieved with statin alone 3, 4

Do NOT initiate statin or statin/ezetimibe in prevalent hemodialysis patients 3, 4

KDIGO provides a Grade 2A recommendation against initiating lipid-lowering therapy in most dialysis patients due to substantially smaller relative risk reduction compared to earlier CKD stages 3
However, if patients are already receiving statin or statin/ezetimibe at dialysis initiation, continuation is suggested (Grade 2C) 4
The exception is dialysis patients with pre-existing atherosclerotic cardiovascular disease, where continuation may be reasonable 4

In patients with clinical ASCVD and persistently elevated LDL-C ≥100 mg/dL despite maximally tolerated statin therapy, adding ezetimibe is reasonable (Class IIa) regardless of eGFR, as long as eGFR >15 mL/min/1.73 m² 3
CKD with eGFR 15-59 mL/min/1.73 m² is itself considered a high-risk condition that contributes to "very high-risk" status when combined with major ASCVD events 3

For patients 20-75 years with LDL-C ≥190 mg/dL who achieve <50% LDL-C reduction on maximally tolerated statin and/or have LDL-C ≥100 mg/dL, adding ezetimibe is reasonable (Class IIa) regardless of eGFR 3

Clinical trials demonstrated no increase in toxicity for simvastatin 20 mg/ezetimibe 10 mg combinations in patients with eGFR <30 mL/min/1.73 m² or on dialysis 3
Research studies in hemodialysis patients showed ezetimibe 10 mg daily for 12 weeks reduced LDL-C by 24.9% without musculoskeletal symptoms, elevated creatine kinase, or liver transaminase elevations 5
A study in 37 CKD patients demonstrated ezetimibe safely decreased LDL-C and provided renal protection (decreased proteinuria) without adverse events over 24 weeks 6

Hepatic impairment supersedes renal considerations: Ezetimibe is NOT recommended in moderate to severe hepatic impairment (Child-Pugh B or C) due to unknown effects of increased drug exposure 1
Drug interactions matter more than eGFR: Cyclosporine increases ezetimibe exposure by 240%, requiring careful monitoring regardless of kidney function 1, 2
Cholestyramine reduces ezetimibe absorption by 55%: Administer ezetimibe several hours apart from bile acid sequestrants 1, 2
Post-transplant patients on cyclosporine: One case report showed a 12-fold greater exposure to total ezetimibe in a renal transplant patient with severe renal insufficiency (CrCl 13.2 mL/min/1.73 m²) receiving cyclosporine, though this likely reflects the cyclosporine interaction rather than renal impairment alone 1