Ezetimibe, sold as Zetia and as generics, is a prescription drug that lowers LDL cholesterol (low-density lipoprotein, the main cholesterol-carrying particle linked to clogged arteries) by blocking cholesterol absorption in the small intestine. The FDA approved Zetia in October 2002 as a new molecular entity, and generic ezetimibe tablets are also approved (Drugs@FDA). It comes in one strength, 10 mg once daily.
Ezetimibe works differently from statins, so the two are often combined. On its own it lowers LDL-C by about 18%. Added to an ongoing statin it lowers LDL-C by about another 25%. In the IMPROVE-IT outcome trial, adding ezetimibe to simvastatin after an acute coronary syndrome modestly reduced cardiovascular events. People who use anabolic steroids sometimes ask about it because these drugs can raise LDL-C and apo B. No trial has tested ezetimibe in anabolic steroid users.
This page summarizes what the FDA label, the major outcome trials and the published research report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Cholesterol absorption inhibitor (blocks the intestinal sterol transporter NPC1L1) |
| Brands and approval | Zetia (FDA approval October 25, 2002); generics approved (for example ANDA 078560, June 2015) |
| Route | Oral tablet, once daily, with or without food |
| Strength | 10 mg (the only labeled dose) |
| LDL-C lowering (label) | About 18% alone; about 25% extra when added to an ongoing statin |
| Half-life (label) | About 22 h for ezetimibe and its active glucuronide |
| Metabolism | Glucuronidation in gut and liver; minimal CYP450 metabolism |
| Cardiovascular outcomes | IMPROVE-IT (added to simvastatin): HR 0.936 for the primary endpoint; not a labeled indication |
| US status | Prescription only; not a controlled substance |
| WADA status | Not listed on the 2026 Prohibited List |
What it is
Ezetimibe is a small synthetic molecule (an azetidinone) with the formula C₂₄H₂₁F₂NO₃ and a molecular weight of 409.4. It is practically insoluble in water. Each Zetia tablet contains 10 mg (FDA label).
Its target is Niemann-Pick C1-Like 1 (NPC1L1), a transporter on the brush border of the small intestine that takes up cholesterol and plant sterols. The label describes the chain of effects:
- less dietary and biliary cholesterol is absorbed (54% less than placebo in a 2-week study of 18 patients);
- less cholesterol reaches the liver, so liver cholesterol stores fall;
- the liver responds by making more LDL receptors, which clear LDL from the blood.
Statins act at a different step: they block cholesterol synthesis in the liver (see atorvastatin). Because the two mechanisms add up, ezetimibe is most often used on top of a statin.
The label also reports that ezetimibe had no clinically meaningful effect on blood levels of the fat-soluble vitamins A, D and E (113 patients), and did not impair adrenal steroid hormone production (118 patients) (FDA label).
Pharmacokinetics
From the current Zetia label (FDA label):
| Parameter | Value |
|---|---|
| Main circulating form | Ezetimibe-glucuronide, which is also active (80–90% of drug in plasma); parent ezetimibe 10–20% |
| Time to peak | 1–2 h for the glucuronide; 4–12 h for ezetimibe |
| Absolute bioavailability | Cannot be determined (no injectable form exists) |
| Effect of food | No effect on total absorption; high-fat meals raise ezetimibe peak by 38% |
| Protein binding | Over 90% |
| Metabolism | Glucuronide conjugation in the small intestine and liver; minimal oxidative (CYP) metabolism |
| Half-life | About 22 h for both ezetimibe and the glucuronide |
| Recycling | Multiple plasma peaks, consistent with enterohepatic recycling |
| Excretion (radiolabel study, 10 days) | About 78% in feces, 11% in urine |
Some groups have higher exposure:
- Older adults (65 and over): total ezetimibe levels about 2-fold higher, which the label calls not clinically meaningful.
- Liver disease: exposure about 1.7-fold higher with mild impairment and 3- to 6-fold higher with moderate or severe impairment. The label does not recommend ezetimibe for moderate or severe hepatic impairment (Child-Pugh B or C).
- Severe kidney disease: exposure about 1.5-fold higher. No dose change is needed.
- Women: levels under 20% higher than in men.
Approved medical use
The label approves ezetimibe, as an adjunct to diet, for these uses (FDA label):
- Primary hyperlipidemia in adults, including heterozygous familial hypercholesterolemia (HeFH, an inherited cause of high LDL): with a statin, or alone when additional LDL-C lowering therapy is not possible.
- HeFH in children 10 and older: with a statin.
- Mixed hyperlipidemia in adults: with fenofibrate.
- Homozygous familial hypercholesterolemia (HoFH) in adults and children 10 and older: with a statin and other LDL-lowering therapies.
- Homozygous sitosterolemia in adults and children 9 and older: a rare inherited disease in which plant sterols build up in the blood.
The labeled dose for every indication is 10 mg once daily, with or without food. The label advises checking LDL-C as early as 4 weeks after starting. A missed dose should be taken as soon as possible, but the next dose should not be doubled. Ezetimibe should be taken at least 2 hours before or 4 hours after a bile acid sequestrant such as cholestyramine.
The label does not include a claim that ezetimibe reduces heart attacks or strokes. Its indications are all based on lowering LDL-C or plant sterols.
What the research shows
LDL lowering alone
In two 12-week placebo-controlled trials in 1,719 adults with primary hyperlipidemia, ezetimibe 10 mg produced these mean changes from untreated baseline (pooled data) (FDA label):
| Group | n | Total-C | LDL-C | Apo B | Non-HDL-C |
|---|---|---|---|---|---|
| Placebo | 431 | 0% | +1% | −2% | +1% |
| Ezetimibe 10 mg | 1,288 | −13% | −18% | −16% | −16% |
Apo B is the main protein on LDL and other atherogenic particles, so it acts as a particle count. Non-HDL-C is total cholesterol minus HDL-C. The label states that the maximal or near-maximal response is generally reached within 2 weeks, and that LDL-C reduction was consistent across age, sex and baseline LDL-C.
LDL lowering with a statin
Added to an ongoing statin. In an 8-week placebo-controlled trial, 769 patients already on a statin who had not reached their LDL-C goal received ezetimibe or placebo on top. LDL-C fell a further 25% with ezetimibe vs 4% with placebo. Apo B fell 19% vs 3%, and non-HDL-C 23% vs 3%. The statins were mostly atorvastatin (40%) and simvastatin (31%) (FDA label).
Started together with a statin. Four 12-week trials (2,382 patients) compared each statin dose alone with the same dose plus ezetimibe. LDL-C changes from untreated baseline for the atorvastatin trial were:
| Atorvastatin dose | Atorvastatin alone | Atorvastatin + ezetimibe |
|---|---|---|
| 10 mg | −37% | −53% |
| 20 mg | −42% | −54% |
| 40 mg | −45% | −56% |
| 80 mg | −54% | −61% |
| Ezetimibe alone | — | −20% |
The simvastatin, pravastatin and lovastatin trials showed the same pattern. For example, simvastatin 10 mg plus ezetimibe (−46%) lowered LDL-C about as much as simvastatin 80 mg alone (−45%). In all four trials, adding ezetimibe to the lowest statin dose gave a larger extra LDL-C drop than any single doubling of the statin dose.
With fenofibrate. In a 12-week trial in 625 patients with mixed hyperlipidemia, LDL-C fell 20% with ezetimibe plus fenofibrate 160 mg, vs 13% with ezetimibe alone and 6% with fenofibrate alone.
Inherited disorders. In 248 adolescents with HeFH, ezetimibe plus simvastatin lowered LDL-C 15% more than simvastatin alone at week 6 (95% CI 12–18%). In 50 patients with HoFH, ezetimibe added to atorvastatin or simvastatin lowered LDL-C by 21%, vs 7% for raising the statin from 40 to 80 mg. In 37 patients with homozygous sitosterolemia, ezetimibe lowered plasma sitosterol by 21% and campesterol by 24% over 8 weeks (FDA label).
Cardiovascular outcomes
| Trial | Population (n) | Comparison | Follow-up | Main result |
|---|---|---|---|---|
| IMPROVE-IT | Hospitalized for acute coronary syndrome in the prior 10 days (18,144) | Simvastatin 40 mg + ezetimibe vs simvastatin 40 mg + placebo | Median 6 years | Primary composite at 7 years: 32.7% vs 34.7%; HR 0.936 (95% CI 0.89–0.99) |
| SHARP | Chronic kidney disease, no prior heart attack or revascularization (9,270) | Simvastatin 20 mg + ezetimibe vs placebo | Median 4.9 years | Major atherosclerotic events: 11.3% vs 13.4%; RR 0.83 (95% CI 0.74–0.94) |
| SEAS | Mild-to-moderate asymptomatic aortic stenosis (1,873) | Simvastatin 40 mg + ezetimibe vs placebo | Median 52.2 months | Primary composite: 35.3% vs 38.2%; HR 0.96 (95% CI 0.83–1.12), not significant |
| RACING | Established atherosclerotic disease, South Korea (3,780) | Rosuvastatin 10 mg + ezetimibe vs rosuvastatin 20 mg, open label | 3 years | Primary composite: 9.1% vs 9.9%; non-inferior |
| EWTOPIA 75 | Age 75 or older, high LDL-C, no coronary disease, Japan (3,796 randomized) | Ezetimibe 10 mg vs usual care, open label | Median 4.1 years | Primary composite: HR 0.66 (95% CI 0.50–0.86) |
Sources: Cannon et al., NEJM 2015; Baigent et al., Lancet 2011; Rossebø et al., NEJM 2008; Kim et al., Lancet 2022; Ouchi et al., Circulation 2019.
Key details:
- IMPROVE-IT is the main test of ezetimibe itself, because both arms got the same statin. The time-weighted average LDL-C was 53.7 mg/dL with ezetimibe vs 69.5 mg/dL without. The primary endpoint combined cardiovascular death, nonfatal heart attack, unstable angina needing hospitalization, coronary revascularization after 30 days, and nonfatal stroke. The absolute difference at 7 years was 2.0 percentage points. Muscle, gallbladder, liver and cancer events were similar in both groups.
- SHARP tested the combination against placebo, so it cannot separate ezetimibe’s effect from simvastatin’s. Non-hemorrhagic stroke (RR 0.75) and arterial revascularization (RR 0.79) were reduced; the drop in heart attack or coronary death (RR 0.92) was not significant.
- SEAS did not slow aortic valve disease: valve replacement rates were the same (HR 1.00). Ischemic cardiovascular events were fewer on treatment (HR 0.78, 95% CI 0.63–0.97).
- RACING used a non-inferiority margin of 2.0%. LDL-C under 70 mg/dL was reached by 72–75% on the combination vs 55–60% on high-dose rosuvastatin. Stopping or dose reduction due to intolerance was less common with the combination (4.8% vs 8.2%).
- EWTOPIA 75 is the only large outcome trial of ezetimibe without a statin. It was open label and stopped early, about 10% of patients were excluded from the main analysis, and the authors themselves say the size of the benefit should be interpreted with caution. Stroke, all-cause death and adverse events were not different.
A meta-regression of 49 trials (312,175 participants) asked whether non-statin LDL lowering protects as much as statin lowering does. Per 1 mmol/L (about 39 mg/dL) fall in LDL-C, the relative risk of major vascular events was 0.77 (95% CI 0.71–0.84) for statins and 0.75 (95% CI 0.66–0.86) for non-statin therapies that raise LDL receptors, a group that included ezetimibe, diet, bile acid sequestrants and ileal bypass (Silverman et al., JAMA 2016). In other words, ezetimibe’s benefit appears to match its LDL lowering. Because that lowering is moderate, the absolute benefit is also moderate.
Effects on testosterone and other steroid hormones
Cholesterol is the raw material for steroid hormones, so lipid drugs are sometimes studied for effects on testosterone. The evidence for ezetimibe is limited to the label statement above and two small studies in which ezetimibe was given with a statin:
| Study | Design | Groups | Hormone findings |
|---|---|---|---|
| Kanat et al., J Endocrinol Invest 2009 (MODEST) | Open-label randomized crossover, 98 patients with type 2 diabetes, 3 months per arm | Atorvastatin 10 mg + ezetimibe vs atorvastatin 80 mg | DHEAS, testosterone and estradiol fell in both groups as LDL fell; cortisol fell only on atorvastatin 80 mg |
| Krysiak et al., Pharmacol Rep 2015 | Non-randomized, 26 men with coronary disease, 16 weeks | Switched from high-dose statin to lower-dose statin + ezetimibe (12) vs continued high-dose statin (14) | After the switch, LH fell 32% and testosterone rose 20%; testosterone was still lower than in the high-dose statin group at the end |
These studies are small, short and not designed to isolate ezetimibe’s own effect. They do not show whether ezetimibe changes testosterone in healthy men or in men taking exogenous androgens.
Lipid changes with anabolic steroids
Ezetimibe is not approved for, and has not been tested in, people taking anabolic-androgenic steroids (AAS). The data below explain why the question comes up, not whether ezetimibe helps.
- HAARLEM cohort. In a prospective study of 100 men doing a self-administered androgen cycle, LDL-C rose by 0.45 mmol/L (95% CI 0.29–0.61; ≈17 mg/dL) and apo B by 18.2 mg/dL, while HDL-C fell by 0.40 mmol/L and Lp(a) by 37.6%. These values returned to baseline after the cycle (Smit et al., Andrologia 2022).
- Oral vs injectable androgens. A 2026 review notes that orally active androgens consistently raise LDL-C, and that apo B rises mainly with oral androgens. In the HAARLEM cohort, oral use correlated with a larger LDL-C increase (Bond et al., Clin Cardiol 2026). For oral 17α-alkylated steroids, see Anavar.
- Where ezetimibe fits. The same narrative review suggests a statin as the first drug when lipid-lowering treatment is chosen, and lists ezetimibe, bempedoic acid and PCSK9 inhibitors as alternatives if statin side effects persist. It also suggests apo B or non-HDL-C targets, because LDL-C may understate particle number in this group. The authors state that empirical data on lipid-lowering drugs specific to androgen abusers are currently lacking (Bond et al., Clin Cardiol 2026).
What is not known:
- No trial in AAS users. No study has measured ezetimibe’s effect on LDL-C, apo B or outcomes during androgen use.
- HDL is not its target. The label reports effects on total-C, LDL-C, apo B and non-HDL-C. It does not describe ezetimibe as a way to correct the large HDL-C falls seen with AAS.
- Outcome trials were in older or high-risk patients. IMPROVE-IT, SHARP and EWTOPIA 75 enrolled people with recent heart attacks, kidney disease or age over 75. Their results do not directly apply to young athletes.
Side effects and risks
Ezetimibe has no boxed warning. The label’s warnings cover liver enzyme increases, muscle injury, and the risks of whatever drug it is combined with (FDA label).
Common side effects
Reactions seen in 2% or more and more often than with the comparator:
| Reaction | Placebo (n = 1,159) | Ezetimibe alone (n = 2,396) | Statin alone (n = 9,361) | Ezetimibe + statin (n = 11,308) |
|---|---|---|---|---|
| Upper respiratory tract infection | 2.5% | 4.3% | 2.8% | 2.9% |
| Diarrhea | 3.7% | 4.1% | 2.2% | 2.5% |
| Arthralgia (joint pain) | 2.2% | 3.0% | 2.4% | 2.6% |
| Pain in extremity | 2.5% | 2.7% | 1.9% | 2.1% |
| Fatigue | 1.5% | 2.4% | 1.6% | 2.0% |
| Influenza | 1.5% | 2.0% | 2.1% | 2.2% |
| Myalgia (muscle pain) | — | — | 2.7% | 3.2% |
| Nasopharyngitis | — | — | 3.3% | 3.7% |
Sinusitis (2.8% vs 2.2%) was also listed for ezetimibe alone, and back pain (2.4% vs 2.3%) for the statin combination. The monotherapy trials had a median duration of 12 weeks; the combination trials, 8 weeks.
Liver enzymes
In controlled trials of ezetimibe started together with a statin, consecutive transaminase elevations of 3 times the upper limit of normal (ULN) or more occurred in 1.3% on the combination vs 0.4% on a statin alone. The label advises liver tests as clinically indicated and considering stopping ezetimibe if ALT or AST stays at 3 × ULN or higher. Post-marketing reports include elevations over 5 × ULN and hepatitis (FDA label).
The large outcome trials found little difference in liver problems. In SHARP, hepatitis occurred in 0.5% vs 0.4% (Baigent et al., Lancet 2011), and IMPROVE-IT reported similar hepatic adverse effects in both groups. No study has examined ezetimibe combined with oral 17α-alkylated steroids, which carry their own liver risks.
Muscle
The label warns that ezetimibe may cause myopathy (muscle pain, tenderness or weakness with a raised creatine kinase) and rhabdomyolysis (rapid muscle breakdown). In post-marketing reports, most patients who developed rhabdomyolysis were also taking a statin or another drug with that risk, such as a fibrate. In SHARP, the excess risk of myopathy with simvastatin plus ezetimibe was 2 per 10,000 patients per year (9 vs 5 cases) (Baigent et al., Lancet 2011).
Gallbladder
Ezetimibe and fenofibrate may both increase cholesterol in bile, which can lead to gallstones. In the fenofibrate combination trial, cholecystectomy (gallbladder removal) rates were 1.7% on the combination vs 0.6% on fenofibrate alone. Post-marketing reports include cholelithiasis and cholecystitis (FDA label). In SHARP, gallstones occurred equally often in both arms (2.3% each).
Cancer signal
In SEAS, cancer occurred more often on simvastatin plus ezetimibe (105 vs 70 patients) (Rossebø et al., NEJM 2008). An independent analysis tested this signal using interim data from SHARP and IMPROVE-IT. In those two trials combined there was no overall excess of cancer (313 vs 326; RR 0.96, 95% CI 0.82–1.12), and no significant excess at any site. The authors concluded the data did not provide credible evidence of an effect on cancer (Peto et al., NEJM 2008). The completed trials agreed: cancer was 9.4% vs 9.5% in SHARP, and similar between groups in IMPROVE-IT.
Other reported reactions
Post-marketing reports listed in the label include hypersensitivity reactions (anaphylaxis, angioedema, rash, hives), pancreatitis, thrombocytopenia (low platelets), erythema multiforme, dizziness, headache, paresthesia and depression. The label notes that these reports cannot establish frequency or cause.
Interactions
Ezetimibe is not cleared by cytochrome P450 enzymes and did not change the levels of CYP probe drugs. It changed exposure to warfarin, digoxin, glipizide and an oral contraceptive by 9% or less. The label lists these clinically important interactions (FDA label):
| Co-administered drug | Effect | Label instruction |
|---|---|---|
| Cyclosporine | Total ezetimibe AUC +240% in transplant patients (12-fold in one patient with severe kidney failure); cyclosporine AUC +15% | Monitor cyclosporine levels; weigh the higher ezetimibe exposure against benefit |
| Fibrates | Fenofibrate raised ezetimibe AUC 48%, gemfibrozil 64%; added gallstone risk | Fibrates other than fenofibrate not recommended; check the gallbladder if gallstones are suspected |
| Cholestyramine (bile acid sequestrant) | Total ezetimibe AUC −55%, which may reduce efficacy | Take ezetimibe at least 2 h before or 4 h after |
| Statins | Small changes in either direction; for example rosuvastatin AUC +19%, fluvastatin −39% | Follow the statin’s own label |
When ezetimibe is combined with a statin, fenofibrate or another LDL-lowering drug, the warnings and contraindications of that drug apply too.
Who should not use it
- Allergy to ezetimibe or tablet ingredients: contraindicated.
- When the partner drug is contraindicated: the statin, fenofibrate or other drug’s contraindications apply to the combination.
- Moderate or severe liver impairment: not recommended, because of 3- to 6-fold higher exposure.
- Pregnancy: human data are insufficient. Animal studies at high doses showed no major harm. The label says to use it only if the benefit justifies the risk, and to follow the statin label when the two are combined.
- Breastfeeding: no human data; ezetimibe is present in rat milk.
Monitoring
The label recommends:
- checking LDL-C when clinically appropriate, as early as 4 weeks after starting;
- liver enzyme tests as clinically indicated;
- telling patients to report unexplained muscle pain, tenderness or weakness promptly, especially with fever or malaise.
Legal status
- US: prescription-only drug, approved in 2002 (NDA 021445), with generic tablets also approved, for example ANDA 078560 in June 2015 (Drugs@FDA). It is not a controlled substance.
- Sport: ezetimibe and other lipid-lowering drugs are not named on the WADA 2026 Prohibited List.
Key takeaways
- Blocks cholesterol absorption, not synthesis. Ezetimibe inhibits the intestinal transporter NPC1L1. That complements statins, which block cholesterol production in the liver.
- Moderate LDL lowering. Alone it lowers LDL-C by about 18%. Added to a statin it lowers it about 25% further, often more than doubling the statin dose would.
- Modest outcome benefit. In IMPROVE-IT, adding ezetimibe to simvastatin after an acute coronary syndrome cut the primary endpoint from 34.7% to 32.7% over 7 years. The benefit appears proportional to the LDL drop.
- Generally well tolerated. Side-effect rates were close to placebo. Liver enzyme rises were slightly more common with a statin (1.3% vs 0.4%), and an early cancer signal was not confirmed in larger trials.
- Few interactions. It is not metabolized by CYP enzymes. Cyclosporine, fibrates and bile acid sequestrants are the main interactions.
- No data in steroid users. Anabolic steroids, especially orals, can raise LDL-C and apo B, but no trial has tested ezetimibe in this group.
Sources
- Organon LLC. Zetia (ezetimibe) tablets, for oral use: prescribing information. DailyMed setid 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb, version 8, November 2025. DailyMed.
- US Food and Drug Administration. Drugs@FDA: NDA 021445 (Zetia, original approval October 25, 2002) and ANDA 078560 (ezetimibe, Glenmark, approved June 26, 2015). FDA NDA 021445; FDA ANDA 078560.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397. PubMed.
- Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–2192. PubMed.
- Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343–1356. PubMed.
- Peto R, Emberson J, Landray M, et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008;359(13):1357–1366. PubMed.
- Kim BK, Hong SJ, Lee YJ, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022;400(10349):380–390. PubMed.
- Ouchi Y, Sasaki J, Arai H, et al. Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): a randomized, controlled trial. Circulation. 2019;140(12):992–1003. PubMed.
- Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–1297. PubMed.
- Kanat M, Serin E, Tunckale A, et al. A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with type 2 diabetes (MODEST Study). J Endocrinol Invest. 2009;32(10):852–856. PubMed.
- Krysiak R, Kowalska B, Żmuda W, Okopień B. The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels. Pharmacol Rep. 2015;67(2):305–309. PubMed.
- Smit DL, Grefhorst A, Buijs MM, et al. Prospective study on blood pressure, lipid metabolism and erythrocytosis during and after androgen abuse. Andrologia. 2022;54(4):e14372. PubMed.
- Bond P, Smit DL, Verdegaal T, de Ronde W. Preventing atherosclerotic cardiovascular disease in young male androgen abusers. Clin Cardiol. 2026;49(2):e70257. PubMed; PMC.
- World Anti-Doping Agency. The 2026 Prohibited List. In effect from January 1, 2026. WADA 2026 Prohibited List.