What is ezetimibe used for?

Ezetimibe: Uses and Clinical Applications

Ezetimibe is primarily used to lower LDL cholesterol by inhibiting intestinal cholesterol absorption at the brush border of the small intestine, either as monotherapy or in combination with statins for patients with hypercholesterolemia who need additional lipid lowering beyond statin therapy alone. 1

Mechanism of Action

• Ezetimibe works by preventing intestinal absorption of cholesterol and plant sterols at the brush border of the small intestine 2
• It blocks both dietary cholesterol and resorption of cholesterol derived from intestinal cell breakdown and bile secretions 2
• Specifically targets the Niemann-Pick C1-like 1 (NPC1L1) protein, which is responsible for cholesterol transport across the intestinal membrane 2

Clinical Indications

Ezetimibe is indicated for:

• Monotherapy for patients who need modest LDL-C reductions (15-20%) or cannot tolerate statins 1
• Adjunctive therapy with statins for patients with severe hyperlipidemia who don't reach target LDL-C levels with statin therapy alone 2
• Treatment of homozygous familial sitosterolemia to lower elevated sitosterol and campesterol levels 1
• Combination therapy with fenofibrate for mixed hyperlipidemia 1
• Use in patients with statin intolerance who require lipid-lowering therapy 2

Efficacy

• As monotherapy, ezetimibe reduces LDL-C by approximately 15-20% 2
• When added to statin therapy, ezetimibe provides an additional 20% reduction in LDL-C beyond what is achieved with the statin alone 2
• The IMPROVE-IT trial demonstrated that adding ezetimibe to simvastatin resulted in a significant reduction in cardiovascular events compared to simvastatin alone 2
• Ezetimibe has been shown to be particularly effective in South Asian populations, with similar efficacy to other ethnic groups 2

Dosing and Administration

• Standard dose is 10 mg orally once daily, with or without food 1
• No timing restrictions between doses 3
• No dosage adjustments needed based on age for elderly patients 3
• Can be taken at the same time as statins when used in combination therapy 1

Safety and Tolerability

• Generally well-tolerated with a side effect profile similar to placebo when used as monotherapy 3
• Common adverse effects include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and fatigue 3
• When combined with statins, potential for increased risk of myopathy and hepatic effects, though still generally safe 3
• Baseline liver function tests are recommended before initiating therapy, especially with concomitant statin use 3

Drug Interactions

• Bile acid sequestrants should be taken at least 2 hours before or 4 hours after ezetimibe 3
• Cyclosporine may increase ezetimibe levels 3
• Fibrates may increase the bioavailability of ezetimibe 3
• No significant interactions with most commonly prescribed medications 1

Special Populations

• Safe in mild hepatic impairment, but should be avoided in moderate to severe hepatic disease 3
• No dosage adjustment needed in mild renal insufficiency 3
• Limited data in pregnancy and lactation; use should be avoided 3
• Has been studied in pediatric populations with familial hypercholesterolemia and appears safe and well-tolerated 2

Clinical Pearls

• Ezetimibe works synergistically with statins due to complementary mechanisms of action (intestinal absorption inhibition + hepatic synthesis inhibition)
• Adding ezetimibe to a lower-dose statin often provides similar LDL-C reduction with fewer side effects compared to doubling the statin dose 2
• Consider ezetimibe as a first-line add-on therapy when statin monotherapy fails to achieve target LDL-C levels
• Particularly useful in patients who experience statin-related muscle symptoms at higher statin doses 2