What is the recommended dose of ezetemibe (ezetimibe) for an adult patient with primary hyperlipidemia?

Ezetimibe Dosing for Primary Hyperlipidemia

The recommended dose of ezetimibe for adults with primary hyperlipidemia is 10 mg orally once daily, with or without food. 1, 2, 3

Standard Dosing

• Ezetimibe is administered as a fixed 10 mg oral dose once daily, regardless of patient age, sex, race, or baseline cholesterol levels 1, 2, 3
• The medication can be taken at any time of day (morning or evening) and does not require timing with meals 1, 3
• No dose adjustment is necessary for patients with mild hepatic impairment or mild-to-severe renal insufficiency 4

Timing Considerations with Bile Acid Sequestrants

• When combining ezetimibe with bile acid sequestrants (such as cholestyramine), administer ezetimibe either ≥2 hours before or ≥4 hours after the bile acid sequestrant 1, 2, 3
• This separation is critical because bile acid sequestrants significantly reduce ezetimibe bioavailability if taken simultaneously 4

Expected Efficacy

• As monotherapy, ezetimibe reduces LDL-C by approximately 18% 1, 2, 5
• When added to statin therapy, ezetimibe provides an additional 25% incremental reduction in LDL-C beyond statin alone 1, 2, 5
• The combination of ezetimibe with bempedoic acid can achieve a 38% reduction in LDL-C when added to statin therapy 6

Clinical Indications for Adding Ezetimibe

For patients with atherosclerotic cardiovascular disease (ASCVD):

• Add ezetimibe to maximally tolerated statin therapy when LDL-C remains ≥70 mg/dL 1, 5

For patients with severe primary hypercholesterolemia (LDL-C ≥190 mg/dL):

• Add ezetimibe when patients achieve less than 50% reduction in LDL-C on maximally tolerated statin therapy and/or have LDL-C ≥100 mg/dL 1, 5

For patients with diabetes mellitus:

• Consider adding ezetimibe to maximally tolerated statin therapy in those with 10-year ASCVD risk ≥20% to reduce LDL-C by 50% or more 1

Monitoring

• Assess LDL-C as early as 4 weeks after initiating ezetimibe 3
• Monitor liver enzymes based on statin monitoring guidelines when ezetimibe is combined with statin therapy, as persistent elevations in hepatic transaminases may occur 2

Safety Profile

• Ezetimibe is generally well tolerated with a safety profile similar to placebo 1, 2
• Common adverse effects include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1, 2
• Cases of myopathy and rhabdomyolysis have been reported when used alone or with statins 2

Important Drug Interactions

• Monitor for interactions with cyclosporine, fibrates, and bile acid sequestrants 1, 2, 6
• Avoid concomitant use with simvastatin >20 mg daily or pravastatin >40 mg daily 6
• Cyclosporine increases ezetimibe exposure; carefully monitor cyclosporin levels when initiating ezetimibe 4

Contraindications

• Hypersensitivity to ezetimibe 5
• Moderate to severe hepatic impairment 5
• Avoid use during pregnancy and lactation due to lack of safety data 2, 5

Clinical Pearls

• Ezetimibe is preferred as the initial non-statin agent for most patients requiring additional LDL-C lowering beyond statin therapy due to its tolerability, convenience, single-tablet daily dose, and generic availability 2, 6, 5
• Do not delay adding ezetimibe in ASCVD patients with persistently elevated LDL-C ≥70 mg/dL on statin therapy, as the IMPROVE-IT trial demonstrated clear cardiovascular benefit (reduction in CV death, nonfatal MI, unstable angina, coronary revascularization, and nonfatal stroke over 6 years) 1, 5
• Consider ezetimibe before more expensive PCSK9 inhibitors 5
• If a dose is missed, take it as soon as possible but do not double the next dose 3