Ezetimibe

updated

Ezetimibe is an FDA-approved LDL-lowering medicine (ZETIA, 2002) that blocks intestinal cholesterol absorption, with an 18,144-patient outcome trial (IMPROVE-IT) showing a small added benefit on top of simvastatin. The supplier claim that it lowers LDL without the liver burden of statins, and so suits oral steroid cycles, is not supported as framed: the label reports transaminase elevations and does not recommend it in moderate or severe hepatic impairment, and NIH LiverTox describes both ezetimibe and statins as rare causes of clinically apparent liver injury. A PubMed search on 9 October 2026 for ezetimibe with anabolic steroid terms returned 0 records.

Cholesterol absorption inhibitor (NPC1L1 blocker)

  • FDA approved ZETIA under NDA 021445 on 25 October 2002; generic ezetimibe ANDAs are on record, for example ANDA 207311 approved 12 June 2017.
  • In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe and rose 1% on placebo.
  • IMPROVE-IT (18,144 patients after an acute coronary syndrome, median follow-up 6 years): the primary composite occurred in 32.7% versus 34.7% (HR 0.936, 95% CI 0.89 to 0.99) when ezetimibe was added to simvastatin.
  • When ZETIA was started together with a statin, transaminase elevations of at least 3 times normal occurred in 1.3% versus 0.4% on a statin alone, and the label does not recommend it in moderate or severe hepatic impairment.
  • A PubMed search on 9 October 2026 for ezetimibe with anabolic steroid terms returned 0 records, and none of 20 statin records was a trial or cohort in steroid users.
  • In 100 men on an androgen cycle, LDL cholesterol rose 0.45 mmol/L (95% CI 0.29 to 0.61) and returned to baseline 3 months after the cycle; no lipid-lowering drug was tested.

What is ezetimibe approved to do?

FDA approved ezetimibe as ZETIA on 25 October 2002, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, with a statin or alone when additional LDL-C-lowering therapy is not possible. It has further labeled uses in familial hypercholesterolemia, mixed hyperlipidemia and sitosterolemia.

ZETIA is labeled, in combination with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia. It is also labeled with a statin in children 10 and older with heterozygous familial hypercholesterolemia, with fenofibrate in adults with mixed hyperlipidemia, with a statin and other LDL-C therapies in homozygous familial hypercholesterolemia, and as an adjunct to diet in homozygous familial sitosterolemia (9 and older). The label version used here took effect on 25 November 2025.

FDA approved ZETIA under NDA 021445 on 25 October 2002. Generic ezetimibe ANDAs are on record, for example ANDA 207311 approved 12 June 2017; that is an example, not a confirmed first generic. Approvals outside the United States are not covered here.

Ezetimibe is C24H21F2NO3 (409.4 g/mol, CAS 163222-33-1, PubChem CID 150311). The ZETIA label gives the same empirical formula and molecular weight.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
Drugs@FDA: ZETIA approved 25 October 2002; generics on record

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021445 (ZETIA), with generic ezetimibe applications including ANDA 207311. Dates read from the openFDA Drugs@FDA records.

FDA approved ZETIA under NDA 021445 on 25 October 2002. Generic ezetimibe ANDAs are on record, for example ANDA 207311 approved 12 June 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic ANDA cited is an example, not a confirmed first generic.

Read the original source
PubChem: ezetimibe identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 150311 (ezetimibe).

Ezetimibe: C24H21F2NO3, 409.4 g/mol, CAS 163222-33-1. The ZETIA label gives the same empirical formula and molecular weight.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the LDL and outcome trials find?

Ezetimibe alone lowered LDL-C by 18% in two label trials. Added to simvastatin in IMPROVE-IT it gave a small reduction in cardiovascular events, and in an open-label trial in Japanese adults aged 75 or older it reduced a cardiovascular composite.

In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431), according to the ZETIA label.

IMPROVE-IT randomized 18,144 patients hospitalized for an acute coronary syndrome in the prior 10 days to simvastatin plus ezetimibe or simvastatin plus placebo, with a median follow-up of 6 years (NCT00202878). Time-weighted average LDL cholesterol was 53.7 versus 69.5 mg/dL. The 7-year primary composite (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization 30 days or more after randomization, or nonfatal stroke) occurred in 32.7% versus 34.7% (absolute difference 2.0 percentage points, HR 0.936, 95% CI 0.89 to 0.99).

EWTOPIA 75, an open-label trial with blinded endpoint evaluation at 363 Japanese sites, randomized 3,796 patients aged 75 or older with elevated LDL-C and no coronary artery disease to ezetimibe or usual care, all with dietary counseling. Over a median 4.1 years, ezetimibe reduced the composite of sudden cardiac death, MI, coronary revascularization or stroke (HR 0.66, 95% CI 0.50 to 0.86), with no difference in stroke, all-cause death or adverse events. The authors advise caution because of the open-label design, early termination and follow-up problems.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
IMPROVE-IT: 18,144 patients after ACS, composite 32.7% versus 34.7%

Randomized controlled trial

Cannon CP et al. N Engl J Med. 2015;372(25):2387-97. PMID 26039521.

Time-weighted average LDL cholesterol was 53.7 versus 69.5 mg/dL. The 7-year primary composite (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization 30 days or more after randomization, or nonfatal stroke) occurred in 32.7% versus 34.7% (absolute difference 2.0 percentage points, HR 0.936, 95% CI 0.89 to 0.99). Prespecified muscle, gallbladder and hepatic adverse effects and cancer were similar between groups.

Participants / model
18,144 patients hospitalized for an acute coronary syndrome in the prior 10 days
Treatment
Oral ezetimibe 10 mg added to simvastatin 40 mg, or simvastatin 40 mg plus placebo
Follow-up
Median follow-up of 6 years
Study design
Randomized trial with a placebo comparator added to simvastatin
Funding
not stated in the source

Applies to ezetimibe added to simvastatin after an acute coronary syndrome, not to oral anabolic steroid users.

Read the original source
EWTOPIA 75: 3,796 Japanese adults aged 75 or older, open-label, HR 0.66

Randomized controlled trial

Ouchi Y et al. Circulation. 2019;140(12):992-1003. PMID 31434507.

Over a median 4.1 years, ezetimibe reduced the composite of sudden cardiac death, MI, coronary revascularization or stroke (HR 0.66, 95% CI 0.50 to 0.86), with no difference in stroke, all-cause death or adverse events. The authors advise caution because of the open-label design, early termination and follow-up problems.

Participants / model
3,796 Japanese adults aged 75 or older with elevated LDL-C and no coronary artery disease, at 363 sites
Treatment
Oral ezetimibe 10 mg daily as monotherapy or usual care, all with dietary counseling
Follow-up
Median 4.1 years
Study design
Open-label randomized trial with blinded endpoint evaluation
Funding
not stated in the source

Open-label, terminated early, with follow-up problems; the authors advise caution.

Read the original source

Is ezetimibe a better choice than a statin during oral steroid cycles?

No study compared them. A PubMed search on 9 October 2026 for ezetimibe with anabolic steroid terms returned 0 records, and the same steroid terms with statin terms returned 20 records, none a trial or cohort of a statin in steroid users. The ZETIA label positions ezetimibe with a statin, or alone only when additional LDL-C lowering is not possible.

Sellers say ezetimibe lowers LDL without the liver burden of statins, so it is the better choice during oral steroid cycles. A PubMed search on 9 October 2026 for ezetimibe with anabolic steroid, bodybuilding, nandrolone, stanozolol, oxandrolone, oxymetholone or methyltestosterone terms returned 0 records. The same steroid terms combined with statin terms returned 20 records, none a trial or cohort of a statin in steroid users. No study compared ezetimibe with a statin during oral steroid use in the records reviewed.

The LDL rise the claim targets was measured in one prospective cohort. In 100 men performing a self-directed androgen cycle, LDL cholesterol rose 0.45 mmol/L (95% CI 0.29 to 0.61) and ApoB rose 18.2 mg/dL during use, while HDL cholesterol fell 0.40 mmol/L and Lp(a) fell 37.6%. These values returned to baseline 3 months after the cycle and 1 year after its start. Follow-up was limited to 1 year, so the authors call the cardiovascular impact uncertain, and no lipid-lowering drug was tested.

The ZETIA label positions ezetimibe with a statin, or alone only when additional LDL-C-lowering therapy is not possible. Ezetimibe alone lowers LDL-C less than a statin does, at 18% in the label trials.

PubMed search, 9 October 2026: 0 records for ezetimibe with anabolic steroid terms

PubMed search record

PubMed search run on 9 October 2026: ezetimibe[tiab] AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab] OR nandrolone[tiab] OR stanozolol[tiab] OR oxandrolone[tiab] OR oxymetholone[tiab] OR methyltestosterone[tiab]). 0 records returned.

The search returned 0 records. The same steroid terms combined with statin terms returned 20 records, none a trial or cohort of a statin in anabolic steroid users. No study compared ezetimibe with a statin during oral anabolic steroid use in the records reviewed.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Androgen cycle cohort: LDL cholesterol up 0.45 mmol/L, back to baseline 3 months after

Human study

Smit DL et al. Andrologia. 2022;54(4):e14372. PMID 35014715.

LDL cholesterol rose 0.45 mmol/L (95% CI 0.29 to 0.61) and ApoB 18.2 mg/dL during use, while HDL cholesterol fell 0.40 mmol/L and Lp(a) fell 37.6%. These values returned to baseline 3 months after the cycle and 1 year after its start. Follow-up was limited to 1 year, so the authors call the cardiovascular impact uncertain.

Participants / model
100 men aged 18 or older performing a self-directed androgen cycle
Treatment
Self-administered androgens (observational); no lipid-lowering drug was tested
Follow-up
Follow-up of 1 year
Study design
Prospective cohort study
Funding
not stated in the source

Observational. It measures the lipid change the supplier claim targets, not any treatment for it.

Read the original source
ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source

Is ezetimibe easier on the liver than a statin?

Not as a general rule. The ZETIA label does not recommend ezetimibe in moderate or severe hepatic impairment, where exposure rises 3- to 6-fold, and NIH LiverTox describes both ezetimibe and statins as rare causes of clinically apparent liver injury.

ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure. After a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

For comparison, the CRESTOR label reports transaminases above 3 times normal in 1.1% on rosuvastatin versus 0.5% on placebo in pooled trials, mostly soon after starting, transient and without symptoms, with rare postmarketing fatal and nonfatal hepatic failure reported with statins. CRESTOR is contraindicated in acute liver failure or decompensated cirrhosis. In Child-Pugh A and B liver disease, rosuvastatin AUC rose 5% and 21% (Cmax 60% and 100%) versus normal liver function, a smaller exposure change than the 3- to 6-fold rise the ZETIA label reports for ezetimibe in moderate or severe impairment.

NIH's LiverTox record for ezetimibe, dated 1 December 2021, says it is usually used in combination with other agents, is associated with a low rate of serum aminotransferase elevations, and that clinically apparent liver injury from ezetimibe occurs but is rare. The statin class record says all seven US statins have been associated with mild-to-moderate aminotransferase elevations that are typically transient and asymptomatic, and with rare clinically apparent acute liver injury, most often reported with atorvastatin and simvastatin and least with pravastatin and pitavastatin. Cases with autoimmune features have been reported with atorvastatin, simvastatin, rosuvastatin and fluvastatin, and with their combinations with ezetimibe. Read together, the NIH references describe both ezetimibe and statins as rare causes of clinically apparent liver injury, so ezetimibe is not liver-neutral.

LiverTox's androgenic steroid record (dated 30 May 2020) says many synthetic androgenic steroids can cause cholestatic liver injury and that long-term androgen use is associated with liver tumors, including hepatocellular carcinoma and hepatic adenoma, and with peliosis hepatis. That supports the premise that oral anabolic steroids carry their own liver risk. No record reviewed tested whether ezetimibe or a statin adds to it.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
CRESTOR label, version effective 23 September 2026: transaminases, hepatic impairment exposure

FDA prescribing information

DailyMed, U.S. National Library of Medicine. CRESTOR (rosuvastatin) oral tablets, prescribing information, label version effective 23 September 2026. Set ID 325a5d0e-9a72-4015-9fcd-1655fb504cee.

In pooled placebo-controlled trials, transaminases above 3 times normal occurred in 1.1% on CRESTOR versus 0.5% on placebo, mostly soon after starting, transient, without symptoms, and resolving or improving on continued therapy or after a brief interruption; rare postmarketing fatal and nonfatal hepatic failure has been reported with statins. CRESTOR is contraindicated in acute liver failure or decompensated cirrhosis. In Child-Pugh A and B liver disease, rosuvastatin AUC rose 5% and 21% (Cmax 60% and 100%) versus normal liver function.

Participants / model
Patients in pooled CRESTOR trials; people with hepatic impairment in label PK studies
Treatment
CRESTOR oral tablets
Follow-up
Label version effective 23 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

Used here as the statin comparator. The exposure change in Child-Pugh A and B disease is smaller than the 3- to 6-fold rise the ZETIA label reports for ezetimibe in moderate or severe impairment.

Read the original source
NIH LiverTox, ezetimibe record dated 1 December 2021: rare clinically apparent liver injury

Regulatory record

Ezetimibe. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643425.

Ezetimibe is usually used in combination with other agents, is associated with a low rate of serum aminotransferase elevations, and clinically apparent liver injury from ezetimibe occurs but is rare.

Participants / model
People treated for hypercholesterolemia (reference summary)
Treatment
Oral ezetimibe
Follow-up
Record dated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Reference summary; it describes rates and case patterns, not a trial.

Read the original source
NIH LiverTox, statin class record: rare clinically apparent liver injury

Regulatory record

Statins. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643398.

All seven US statins have been associated with mild-to-moderate aminotransferase elevations that are typically transient and asymptomatic and may resolve even with continued use, and with rare clinically apparent acute liver injury, most often reported with atorvastatin and simvastatin and least with pravastatin and pitavastatin. Cases with autoimmune features have been reported with atorvastatin, simvastatin, rosuvastatin and fluvastatin, and with their combinations with ezetimibe.

Participants / model
People treated with statins (reference summary)
Treatment
Oral statins
Follow-up
References updated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Read together with the ezetimibe record, the NIH reference describes both ezetimibe and statins as rare causes of clinically apparent liver injury.

Read the original source
NIH LiverTox, androgenic steroid record dated 30 May 2020: cholestatic injury, tumors, peliosis hepatis

Regulatory record

Androgenic Steroids. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31644236.

Many synthetic androgenic steroids can cause cholestatic liver injury, and long-term androgen use is associated with liver tumors, including hepatocellular carcinoma and hepatic adenoma, and with peliosis hepatis.

Participants / model
People using androgenic steroids, including illicit use (reference summary)
Treatment
Androgenic and anabolic steroids
Follow-up
Record dated 30 May 2020
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Supports the premise that oral anabolic steroids carry their own liver risk. No record reviewed tested whether ezetimibe or a statin adds to it.

Read the original source

How does ezetimibe work, and what does the body do with it?

Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. It is rapidly conjugated to an active glucuronide, both forms have a half-life of about 22 hours, and multiple plasma peaks suggest enterohepatic recycling.

The ZETIA label says ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1.

Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide. Both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling. About 78% of a radiolabeled dose is recovered in feces and 11% in urine.

Whether the cholestatic liver injury linked to oral anabolic steroids changes ezetimibe or statin exposure is unstudied in the records reviewed.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source

What risks does the label report?

The ZETIA label reports increases in serum transaminases, with postmarketing reports of hepatitis, cholelithiasis and cholecystitis, and does not recommend ezetimibe in moderate or severe hepatic impairment. In IMPROVE-IT, muscle, gallbladder and hepatic adverse effects and cancer were similar between groups.

The ZETIA label reports increases in serum transaminases. In controlled trials where ZETIA was started together with a statin, consecutive transaminase elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone. The label advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis.

In IMPROVE-IT, prespecified muscle, gallbladder and hepatic adverse effects and cancer were similar between groups. In EWTOPIA 75, adverse events did not differ, though the authors advise caution because of the open-label design.

These figures come from people treated for lipid disorders or after an acute coronary syndrome. No study of ezetimibe in people using oral anabolic steroids was found, so its liver safety in that setting is unmeasured.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
IMPROVE-IT: 18,144 patients after ACS, composite 32.7% versus 34.7%

Randomized controlled trial

Cannon CP et al. N Engl J Med. 2015;372(25):2387-97. PMID 26039521.

Time-weighted average LDL cholesterol was 53.7 versus 69.5 mg/dL. The 7-year primary composite (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization 30 days or more after randomization, or nonfatal stroke) occurred in 32.7% versus 34.7% (absolute difference 2.0 percentage points, HR 0.936, 95% CI 0.89 to 0.99). Prespecified muscle, gallbladder and hepatic adverse effects and cancer were similar between groups.

Participants / model
18,144 patients hospitalized for an acute coronary syndrome in the prior 10 days
Treatment
Oral ezetimibe 10 mg added to simvastatin 40 mg, or simvastatin 40 mg plus placebo
Follow-up
Median follow-up of 6 years
Study design
Randomized trial with a placebo comparator added to simvastatin
Funding
not stated in the source

Applies to ezetimibe added to simvastatin after an acute coronary syndrome, not to oral anabolic steroid users.

Read the original source
EWTOPIA 75: 3,796 Japanese adults aged 75 or older, open-label, HR 0.66

Randomized controlled trial

Ouchi Y et al. Circulation. 2019;140(12):992-1003. PMID 31434507.

Over a median 4.1 years, ezetimibe reduced the composite of sudden cardiac death, MI, coronary revascularization or stroke (HR 0.66, 95% CI 0.50 to 0.86), with no difference in stroke, all-cause death or adverse events. The authors advise caution because of the open-label design, early termination and follow-up problems.

Participants / model
3,796 Japanese adults aged 75 or older with elevated LDL-C and no coronary artery disease, at 363 sites
Treatment
Oral ezetimibe 10 mg daily as monotherapy or usual care, all with dietary counseling
Follow-up
Median 4.1 years
Study design
Open-label randomized trial with blinded endpoint evaluation
Funding
not stated in the source

Open-label, terminated early, with follow-up problems; the authors advise caution.

Read the original source

Why does ezetimibe sit in S tier?

FDA approval since 2002, an 18,144-patient outcome trial, an open-label outcome trial in older Japanese adults, and more than two decades of use support the S for the approved uses. The grade does not support describing ezetimibe as liver-neutral or as a better choice than a statin during oral steroid use.

The S applies to lowering LDL cholesterol as labeled. IMPROVE-IT showed a small added benefit on top of simvastatin, and the open-label EWTOPIA 75 trial came with the authors' caution.

The supplier claim is separate and not supported as framed. The label positions ezetimibe with a statin, or alone only when additional LDL-C-lowering therapy is not possible. NIH LiverTox describes both ezetimibe and statins as rare causes of clinically apparent liver injury. Ezetimibe exposure rises 3- to 6-fold in moderate or severe hepatic impairment, where it is not recommended, against a 21% AUC rise for rosuvastatin in Child-Pugh B disease. No study compared the two during oral steroid use.

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
Drugs@FDA: ZETIA approved 25 October 2002; generics on record

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021445 (ZETIA), with generic ezetimibe applications including ANDA 207311. Dates read from the openFDA Drugs@FDA records.

FDA approved ZETIA under NDA 021445 on 25 October 2002. Generic ezetimibe ANDAs are on record, for example ANDA 207311 approved 12 June 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic ANDA cited is an example, not a confirmed first generic.

Read the original source
IMPROVE-IT: 18,144 patients after ACS, composite 32.7% versus 34.7%

Randomized controlled trial

Cannon CP et al. N Engl J Med. 2015;372(25):2387-97. PMID 26039521.

Time-weighted average LDL cholesterol was 53.7 versus 69.5 mg/dL. The 7-year primary composite (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization 30 days or more after randomization, or nonfatal stroke) occurred in 32.7% versus 34.7% (absolute difference 2.0 percentage points, HR 0.936, 95% CI 0.89 to 0.99). Prespecified muscle, gallbladder and hepatic adverse effects and cancer were similar between groups.

Participants / model
18,144 patients hospitalized for an acute coronary syndrome in the prior 10 days
Treatment
Oral ezetimibe 10 mg added to simvastatin 40 mg, or simvastatin 40 mg plus placebo
Follow-up
Median follow-up of 6 years
Study design
Randomized trial with a placebo comparator added to simvastatin
Funding
not stated in the source

Applies to ezetimibe added to simvastatin after an acute coronary syndrome, not to oral anabolic steroid users.

Read the original source
EWTOPIA 75: 3,796 Japanese adults aged 75 or older, open-label, HR 0.66

Randomized controlled trial

Ouchi Y et al. Circulation. 2019;140(12):992-1003. PMID 31434507.

Over a median 4.1 years, ezetimibe reduced the composite of sudden cardiac death, MI, coronary revascularization or stroke (HR 0.66, 95% CI 0.50 to 0.86), with no difference in stroke, all-cause death or adverse events. The authors advise caution because of the open-label design, early termination and follow-up problems.

Participants / model
3,796 Japanese adults aged 75 or older with elevated LDL-C and no coronary artery disease, at 363 sites
Treatment
Oral ezetimibe 10 mg daily as monotherapy or usual care, all with dietary counseling
Follow-up
Median 4.1 years
Study design
Open-label randomized trial with blinded endpoint evaluation
Funding
not stated in the source

Open-label, terminated early, with follow-up problems; the authors advise caution.

Read the original source
CRESTOR label, version effective 23 September 2026: transaminases, hepatic impairment exposure

FDA prescribing information

DailyMed, U.S. National Library of Medicine. CRESTOR (rosuvastatin) oral tablets, prescribing information, label version effective 23 September 2026. Set ID 325a5d0e-9a72-4015-9fcd-1655fb504cee.

In pooled placebo-controlled trials, transaminases above 3 times normal occurred in 1.1% on CRESTOR versus 0.5% on placebo, mostly soon after starting, transient, without symptoms, and resolving or improving on continued therapy or after a brief interruption; rare postmarketing fatal and nonfatal hepatic failure has been reported with statins. CRESTOR is contraindicated in acute liver failure or decompensated cirrhosis. In Child-Pugh A and B liver disease, rosuvastatin AUC rose 5% and 21% (Cmax 60% and 100%) versus normal liver function.

Participants / model
Patients in pooled CRESTOR trials; people with hepatic impairment in label PK studies
Treatment
CRESTOR oral tablets
Follow-up
Label version effective 23 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

Used here as the statin comparator. The exposure change in Child-Pugh A and B disease is smaller than the 3- to 6-fold rise the ZETIA label reports for ezetimibe in moderate or severe impairment.

Read the original source
NIH LiverTox, ezetimibe record dated 1 December 2021: rare clinically apparent liver injury

Regulatory record

Ezetimibe. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643425.

Ezetimibe is usually used in combination with other agents, is associated with a low rate of serum aminotransferase elevations, and clinically apparent liver injury from ezetimibe occurs but is rare.

Participants / model
People treated for hypercholesterolemia (reference summary)
Treatment
Oral ezetimibe
Follow-up
Record dated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Reference summary; it describes rates and case patterns, not a trial.

Read the original source
NIH LiverTox, statin class record: rare clinically apparent liver injury

Regulatory record

Statins. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643398.

All seven US statins have been associated with mild-to-moderate aminotransferase elevations that are typically transient and asymptomatic and may resolve even with continued use, and with rare clinically apparent acute liver injury, most often reported with atorvastatin and simvastatin and least with pravastatin and pitavastatin. Cases with autoimmune features have been reported with atorvastatin, simvastatin, rosuvastatin and fluvastatin, and with their combinations with ezetimibe.

Participants / model
People treated with statins (reference summary)
Treatment
Oral statins
Follow-up
References updated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Read together with the ezetimibe record, the NIH reference describes both ezetimibe and statins as rare causes of clinically apparent liver injury.

Read the original source
PubMed search, 9 October 2026: 0 records for ezetimibe with anabolic steroid terms

PubMed search record

PubMed search run on 9 October 2026: ezetimibe[tiab] AND (anabolic steroid*[tiab] OR anabolic-androgenic[tiab] OR anabolic androgenic[tiab] OR bodybuild*[tiab] OR nandrolone[tiab] OR stanozolol[tiab] OR oxandrolone[tiab] OR oxymetholone[tiab] OR methyltestosterone[tiab]). 0 records returned.

The search returned 0 records. The same steroid terms combined with statin terms returned 20 records, none a trial or cohort of a statin in anabolic steroid users. No study compared ezetimibe with a statin during oral anabolic steroid use in the records reviewed.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

ZETIA label, version effective 25 November 2025: indications, LDL-C, PK, liver enzymes

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ZETIA (ezetimibe) oral tablets, prescribing information, label version effective 25 November 2025. Set ID 174e45e0-45bb-48b7-9e60-8f6cfc1d22bb.

The label approves ZETIA, with a statin or alone when additional LDL-C-lowering therapy is not possible, as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, with further labeled uses in children 10 and older with HeFH, mixed hyperlipidemia, homozygous familial hypercholesterolemia and homozygous familial sitosterolemia. Ezetimibe blocks intestinal cholesterol absorption through the sterol transporter NPC1L1. In two 12-week placebo-controlled monotherapy trials in 1,719 patients with primary hyperlipidemia, pooled LDL-C fell 18% on ezetimibe (1,288 patients) and rose 1% on placebo (431). Ezetimibe is rapidly conjugated in the small intestine and liver to an active glucuronide; both forms have a half-life of about 22 hours, with multiple plasma peaks suggesting enterohepatic recycling, and about 78% of a radiolabeled dose is recovered in feces and 11% in urine. The label reports increases in serum transaminases: consecutive elevations of at least 3 times the upper limit of normal occurred in 1.3% versus 0.4% on a statin alone when ZETIA was started together with a statin. It advises liver tests as clinically indicated and considering withdrawal if elevations of at least 3 times normal persist. Postmarketing reports include transaminase elevations above 5 times normal, hepatitis, cholelithiasis and cholecystitis. ZETIA is not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) because of increased exposure: after a single dose, total ezetimibe AUC was about 1.7-fold higher in mild impairment and about 3- to 4-fold higher (5- to 6-fold for unconjugated ezetimibe) in moderate or severe impairment, and about 4-fold higher on days 1 and 14 of daily dosing in moderate impairment.

Participants / model
Adults and children with the labeled lipid disorders; patients in controlled lipid trials; people with graded hepatic impairment in label PK studies
Treatment
ZETIA oral tablets, alone or with a statin
Follow-up
Label version effective 25 November 2025
Study design
FDA prescribing information
Funding
not stated in the source

Label-level statements. The page does not reproduce label dosing.

Read the original source
Drugs@FDA: ZETIA approved 25 October 2002; generics on record

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 021445 (ZETIA), with generic ezetimibe applications including ANDA 207311. Dates read from the openFDA Drugs@FDA records.

FDA approved ZETIA under NDA 021445 on 25 October 2002. Generic ezetimibe ANDAs are on record, for example ANDA 207311 approved 12 June 2017.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 2002 to 2017 in the records returned
Study design
FDA application records
Funding
not stated in the source

The generic ANDA cited is an example, not a confirmed first generic.

Read the original source
IMPROVE-IT: 18,144 patients after ACS, composite 32.7% versus 34.7%

Randomized controlled trial

Cannon CP et al. N Engl J Med. 2015;372(25):2387-97. PMID 26039521.

Time-weighted average LDL cholesterol was 53.7 versus 69.5 mg/dL. The 7-year primary composite (cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization 30 days or more after randomization, or nonfatal stroke) occurred in 32.7% versus 34.7% (absolute difference 2.0 percentage points, HR 0.936, 95% CI 0.89 to 0.99). Prespecified muscle, gallbladder and hepatic adverse effects and cancer were similar between groups.

Participants / model
18,144 patients hospitalized for an acute coronary syndrome in the prior 10 days
Treatment
Oral ezetimibe 10 mg added to simvastatin 40 mg, or simvastatin 40 mg plus placebo
Follow-up
Median follow-up of 6 years
Study design
Randomized trial with a placebo comparator added to simvastatin
Funding
not stated in the source

Applies to ezetimibe added to simvastatin after an acute coronary syndrome, not to oral anabolic steroid users.

Read the original source
EWTOPIA 75: 3,796 Japanese adults aged 75 or older, open-label, HR 0.66

Randomized controlled trial

Ouchi Y et al. Circulation. 2019;140(12):992-1003. PMID 31434507.

Over a median 4.1 years, ezetimibe reduced the composite of sudden cardiac death, MI, coronary revascularization or stroke (HR 0.66, 95% CI 0.50 to 0.86), with no difference in stroke, all-cause death or adverse events. The authors advise caution because of the open-label design, early termination and follow-up problems.

Participants / model
3,796 Japanese adults aged 75 or older with elevated LDL-C and no coronary artery disease, at 363 sites
Treatment
Oral ezetimibe 10 mg daily as monotherapy or usual care, all with dietary counseling
Follow-up
Median 4.1 years
Study design
Open-label randomized trial with blinded endpoint evaluation
Funding
not stated in the source

Open-label, terminated early, with follow-up problems; the authors advise caution.

Read the original source
NIH LiverTox, ezetimibe record dated 1 December 2021: rare clinically apparent liver injury

Regulatory record

Ezetimibe. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643425.

Ezetimibe is usually used in combination with other agents, is associated with a low rate of serum aminotransferase elevations, and clinically apparent liver injury from ezetimibe occurs but is rare.

Participants / model
People treated for hypercholesterolemia (reference summary)
Treatment
Oral ezetimibe
Follow-up
Record dated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Reference summary; it describes rates and case patterns, not a trial.

Read the original source
NIH LiverTox, statin class record: rare clinically apparent liver injury

Regulatory record

Statins. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643398.

All seven US statins have been associated with mild-to-moderate aminotransferase elevations that are typically transient and asymptomatic and may resolve even with continued use, and with rare clinically apparent acute liver injury, most often reported with atorvastatin and simvastatin and least with pravastatin and pitavastatin. Cases with autoimmune features have been reported with atorvastatin, simvastatin, rosuvastatin and fluvastatin, and with their combinations with ezetimibe.

Participants / model
People treated with statins (reference summary)
Treatment
Oral statins
Follow-up
References updated 1 December 2021
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Read together with the ezetimibe record, the NIH reference describes both ezetimibe and statins as rare causes of clinically apparent liver injury.

Read the original source
CRESTOR label, version effective 23 September 2026: transaminases, hepatic impairment exposure

FDA prescribing information

DailyMed, U.S. National Library of Medicine. CRESTOR (rosuvastatin) oral tablets, prescribing information, label version effective 23 September 2026. Set ID 325a5d0e-9a72-4015-9fcd-1655fb504cee.

In pooled placebo-controlled trials, transaminases above 3 times normal occurred in 1.1% on CRESTOR versus 0.5% on placebo, mostly soon after starting, transient, without symptoms, and resolving or improving on continued therapy or after a brief interruption; rare postmarketing fatal and nonfatal hepatic failure has been reported with statins. CRESTOR is contraindicated in acute liver failure or decompensated cirrhosis. In Child-Pugh A and B liver disease, rosuvastatin AUC rose 5% and 21% (Cmax 60% and 100%) versus normal liver function.

Participants / model
Patients in pooled CRESTOR trials; people with hepatic impairment in label PK studies
Treatment
CRESTOR oral tablets
Follow-up
Label version effective 23 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

Used here as the statin comparator. The exposure change in Child-Pugh A and B disease is smaller than the 3- to 6-fold rise the ZETIA label reports for ezetimibe in moderate or severe impairment.

Read the original source
NIH LiverTox, androgenic steroid record dated 30 May 2020: cholestatic injury, tumors, peliosis hepatis

Regulatory record

Androgenic Steroids. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31644236.

Many synthetic androgenic steroids can cause cholestatic liver injury, and long-term androgen use is associated with liver tumors, including hepatocellular carcinoma and hepatic adenoma, and with peliosis hepatis.

Participants / model
People using androgenic steroids, including illicit use (reference summary)
Treatment
Androgenic and anabolic steroids
Follow-up
Record dated 30 May 2020
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

Supports the premise that oral anabolic steroids carry their own liver risk. No record reviewed tested whether ezetimibe or a statin adds to it.

Read the original source
Androgen cycle cohort: LDL cholesterol up 0.45 mmol/L, back to baseline 3 months after

Human study

Smit DL et al. Andrologia. 2022;54(4):e14372. PMID 35014715.

LDL cholesterol rose 0.45 mmol/L (95% CI 0.29 to 0.61) and ApoB 18.2 mg/dL during use, while HDL cholesterol fell 0.40 mmol/L and Lp(a) fell 37.6%. These values returned to baseline 3 months after the cycle and 1 year after its start. Follow-up was limited to 1 year, so the authors call the cardiovascular impact uncertain.

Participants / model
100 men aged 18 or older performing a self-directed androgen cycle
Treatment
Self-administered androgens (observational); no lipid-lowering drug was tested
Follow-up
Follow-up of 1 year
Study design
Prospective cohort study
Funding
not stated in the source

Observational. It measures the lipid change the supplier claim targets, not any treatment for it.

Read the original source
PubChem: ezetimibe identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 150311 (ezetimibe).

Ezetimibe: C24H21F2NO3, 409.4 g/mol, CAS 163222-33-1. The ZETIA label gives the same empirical formula and molecular weight.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Ezetimibe in S tier?

S fits an approved medicine with an 18,144-patient outcome trial, an open-label outcome trial in Japanese adults aged 75 or older, and more than two decades of use for lowering LDL cholesterol. The grade covers the approved uses. It does not support describing ezetimibe as liver-neutral or as a better choice than a statin during oral steroid use, which no study tested.