From the Guidelines
Ezetimibe is a cholesterol-lowering medication that works by inhibiting the absorption of cholesterol in the small intestine, specifically targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein, and is recommended as an adjunct to diet to reduce LDL-C, either alone or in combination with statin therapy, with a standard dose of 10 mg once daily, as supported by the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering 1.
Mode of Action
Ezetimibe reduces the amount of dietary and biliary cholesterol absorbed, leading to decreased cholesterol levels in the bloodstream, by blocking the NPC1L1 protein on intestinal cells, which is responsible for cholesterol uptake from the gut.
Therapeutic Effects
Therapeutically, ezetimibe typically reduces LDL cholesterol by 15-20% when used as monotherapy and provides additional 15-25% reduction when added to statin therapy, making it valuable for patients who cannot tolerate high-dose statins or who need additional LDL lowering, as shown in the IMPROVE-IT trial 2.
Side Effects
Common side effects are generally mild and include diarrhea, abdominal pain, arthralgia, and fatigue, while serious side effects are rare but may include myopathy (especially when combined with statins), hepatic dysfunction, and hypersensitivity reactions, as reported in the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering 1.
Clinical Use
Ezetimibe is particularly useful for patients with statin intolerance, those already on maximum statin doses who need additional LDL reduction, or as initial therapy in patients with moderate hypercholesterolemia and contraindications to statins, as recommended by the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering 1.
Key Considerations
- The standard dose of ezetimibe is 10 mg once daily, taken with or without food.
- Ezetimibe can be used alone or in combination with statins for enhanced lipid-lowering effects.
- Unlike statins, ezetimibe does not significantly affect triglycerides or raise HDL cholesterol.
- Ezetimibe is generally well tolerated, with a low risk of serious side effects, as supported by the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering 1.
From the FDA Drug Label
Monotherapy In 10 double-blind, placebo-controlled clinical trials, 2,396 patients with primary hyperlipidemia (age range 9 to 86 years; 50% female, 90% White, 5% Black or African American, 2% Asian, 3% other races; 3% identified as Hispanic or Latino ethnicity) and elevated LDL-C were treated with ezetimibe tablets 10 mg daily for a median treatment duration of 12 weeks (range 0 to 39 weeks) Adverse reactions reported in ≥2% of patients treated with ezetimibe tablets and at an incidence greater than placebo in placebo-controlled studies of ezetimibe tablets are shown in Table 1 TABLE 1: Adverse Reactions Occurring ≥2% and Greater than Placebo in Ezetimibe Tablets -treated Patients Adverse Reaction Placebo (%) n = 1,159 Ezetimibe Tablets 10 mg (%) n = 2,396 Upper respiratory tract infection 2.5 4.3 Diarrhea 3.7 4.1 Arthralgia 2.2 3.0 Sinusitis 2.2 2.8 Pain in extremity 2.5 2.7 Fatigue 1.5 2.4 Influenza 1.5 2. 0 Combination with a Statin In 28 double-blind, controlled (placebo or active-controlled) clinical trials, 11,308 patients with primary hyperlipidemia (age range 10 to 93 years, 48% female, 85% White, 7% Black or African American, 3% Asian, 5% other races; 4% identified as Hispanic or Latino ethnicity) and elevated LDL-C were treated with ezetimibe tablets 10 mg/day concurrently with or added to on-going statin therapy for a median treatment duration of 8 weeks (range 0 to 112 weeks). The incidence of consecutive increased transaminases (≥3 X ULN) was higher in patients receiving ezetimibe tablets administered with statins (1.3%) than in patients treated with statins alone (0. 4%). Adverse reactions reported in ≥2% of patients treated with ezetimibe tablets + statin and at an incidence greater than statin are shown in Table 2 TABLE 2: Adverse Reactions Occurring ≥2% in Ezetimibe Tablets -treated Patients Coadministered with a Statin and at an Incidence Greater than Statin Adverse Reaction All Statins (%) n = 9,361 Ezetimibe Tablets + All Statins (%) n = 11,308 Nasopharyngitis 3.3 3.7 Myalgia 2.7 3.2 Upper respiratory tract infection 2.8 2.9 Arthralgia 2.4 2.6 Diarrhea 2.2 2.5 Back pain 2.3 2.4 Influenza 2.1 2. 2 Pain in extremity 1.9 2.1 Fatigue 1.6 2. 0
The mode of action of ezetimibe is not explicitly stated in the provided text. The side effects of ezetimibe include:
- Upper respiratory tract infection
- Diarrhea
- Arthralgia
- Sinusitis
- Pain in extremity
- Fatigue
- Influenza The therapeutic effects of ezetimibe are not explicitly stated in the provided text, but it is used to treat primary hyperlipidemia and elevated LDL-C 3.
From the Research
Mode of Action
- Ezetimibe inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids 4, 5.
- It localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes by binding to Niemann-Pick C1 Like 1 (NPC1L1) 5, 6.
- Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption 5.
Therapeutic Effects
- Ezetimibe reduces low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5% 4.
- It has been shown to be effective in reducing plasma total and LDL-Cholesterol levels in patients with primary hypercholesterolemia, both as monotherapy and in combination with statins 4, 5, 6.
- Ezetimibe may also favorably affect other parameters that could potentially further reduce atherosclerotic coronary heart disease risk, such as raising HDL-cholesterol and lowering levels of triglycerides, non-HDL-cholesterol, apolipoprotein B, and remnant-like particle cholesterol 7.
Side Effects
- Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins 4.
- It has an excellent safety and tolerability profile combined with once-daily dosing, making it an attractive adjunct therapy for the treatment of hypercholesterolemia 6.
- Unlike other intestinally acting lipid-lowering agents, ezetimibe does not adversely affect triglyceride levels and, due to its minimal systemic absorption, drug interactions are few 4.