Class: Cholesterol Absorption Inhibitors
VA Class: CV350
Chemical Name: [3R-[3α(S*),4β]]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone
Molecular Formula: C24H21F2NO3
CAS Number: 163222-33-1
Brands: Zetia
Medically reviewed by Drugs.com. Last updated on June 16, 2020.
Introduction
Antilipemic agent;1 cholesterol absorption inhibitor.2 4 5 8
Uses for Ezetimibe
Primary Hyperlipidemia and Mixed Dyslipidemia
Use alone or in combination with a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and non-HDL-cholesterol concentrations in the treatment of primary (heterozygous familial and nonfamilial) hyperlipidemia.1 20
Effects on cardiovascular morbidity and mortality not established.1
Use in fixed combination with simvastatin as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apo B, triglyceride, and non-HDL-cholesterol concentrations, and to increase HDL-cholesterol concentrations in the treatment of primary hyperlipidemia or mixed dyslipidemia.20 In the IMPROVE-IT study, addition of ezetimibe to simvastatin therapy further reduced LDL cholesterol and improved cardiovascular outcomes in post-acute coronary syndrome (ACS) patients.309 In the SHARP study, fixed-combination preparation of simvastatin and ezetimibe reduced risk of major vascular and atherosclerotic events in patients with chronic kidney disease.20 308
Use in combination with fenofibrate as an adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apo B, and non-HDL-cholesterol concentrations in the treatment of mixed dyslipidemia.1 Effects on cardiovascular morbidity and mortality not established.1 Use with a fibric acid derivative other than fenofibrate not studied and currently not recommended.1 (See Specific Drugs under Interactions.)
Produces negligible increases in HDL-cholesterol concentrations.1 2
Drug therapy is not a substitute for but an adjunct to nondrug therapies and measures (e.g., dietary management, weight control, physical activity, management of potentially contributory disease), which should be continued when drug therapy is initiated.9 10 11
ACC/AHA cholesterol management guideline states that nonstatin drugs (e.g., ezetimibe) do not provide acceptable atherosclerotic cardiovascular disease (ASCVD) risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD.350 However, may be useful as adjuncts to statin therapy in high-risk patients (e.g., patients with ASCVD, LDL-cholesterol concentrations ≥190 mg/dL, or diabetes mellitus) who have a less-than-anticipated response to statins, are unable to tolerate a less-than-recommended intensity of a statin, or are completely intolerant to statin therapy, particularly when evidence from randomized controlled studies suggest the nonstatin drug further reduces ASCVD events when added to statin therapy.350 Select nonstatin drug based on favorable benefit-risk ratio (i.e., demonstrated benefit of ASCVD risk reduction outweighs risks of adverse effects and drug interactions) and patient preferences.350 Current recommendations from ACC/AHA regarding prevention of ASCVD and lifestyle modifications to reduce cardiovascular risk are available at or [Web]352
Homozygous Familial Hypercholesterolemia
Use in combination with atorvastatin or simvastatin to decrease elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL apheresis) or when such therapies are not available.1 20
Effects in patients currently undergoing LDL apheresis compared with those in patients not undergoing the procedure not established.4 Effects on clinical outcome and modification of other disease parameters (e.g., xanthoma formation, regression of atherosclerosis) not established.4
Homozygous Familial Sitosterolemia (Phytosterolemia)
Adjunct to dietary therapy to decrease elevated serum sitosterol and campesterol concentrations in patients with homozygous familial sitosterolemia.1 6 8
Reductions in sitosterol and campesterol concentrations were consistent between patients receiving ezetimibe with or without bile acid sequestrants.1
Effect of reducing plasma concentrations of sitosterol and campesterol on cardiovascular morbidity and mortality not established.1
Ezetimibe Dosage and Administration
General
-
Patients should be placed on a standard cholesterol-lowering diet before initiation of ezetimibe therapy and should remain on this diet during treatment with the drug.1
Administration
Oral Administration
Administer orally without regard to meals.1
Combination therapy with a statin or fenofibrate: May administer ezetimibe at same time as the statin or fenofibrate, in accordance with recommended dosing schedule for these drugs.1
Combination therapy with a bile acid sequestrant: Administer ≥2 hours before or ≥4 hours after bile acid sequestrant.1
Ezetimibe/simvastatin fixed-combination preparation: Administer orally in the evening without regard to meals.20
Dosage
Pediatric Patients
Dyslipidemias
Primary Hyperlipidemia and Mixed Dyslipidemia
OralChildren ≥10 years of age: 10 mg once daily.1
Homozygous Familial Hypercholesterolemia
OralChildren ≥10 years of age: 10 mg once daily.1
Homozygous Familial Sitosterolemia
OralChildren ≥10 years of age: 10 mg once daily.1
Adults
Dyslipidemias
Primary Hyperlipidemia and Mixed Dyslipidemia
Oral10 mg once daily.1
Ezetimibe/simvastatin fixed combination (Vytorin): Initially, ezetimibe 10 mg/simvastatin 10 mg or ezetimibe 10 mg/simvastatin 20 mg once daily in the evening.20 In patients requiring LDL-cholesterol reductions ≥55%, may initiate therapy with ezetimibe 10 mg/simvastatin 40 mg once daily in the absence of moderate to severe renal impairment (GFR <60 mL/minute per 1.73 m2).20 Determine serum cholesterol concentrations ≥2 weeks after initiation or titration of therapy and adjust dosage as needed.20 Usual maintenance dosage range is ezetimibe 10 mg and simvastatin 10–40 mg once daily.20 If LDL-cholesterol target goal cannot be achieved with ezetimibe 10 mg/simvastatin 40 mg once daily, do not increase dosage; instead, switch to an alternative antilipemic agent(s) that provides greater LDL-cholesterol reduction.20 Restrict use of ezetimibe 10 mg/simvastatin 80 mg dosage.20 (See Prescribing Limits under Dosage and Administration.)
Homozygous Familial Hypercholesterolemia
Oral10 mg once daily.1
Ezetimibe/simvastatin fixed combination (Vytorin): Ezetimibe 10 mg/simvastatin 40 mg once daily in the evening.20 Use as adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.20
Homozygous Familial Sitosterolemia
Oral10 mg once daily.1
Prescribing Limits
Adults
Oral
Restrict use of ezetimibe 10 mg/simvastatin 80 mg dosage to patients who have been receiving long-term therapy (e.g., ≥12 months) at this dosage without evidence of adverse muscular effects.20 In patients currently tolerating the ezetimibe 10 mg/simvastatin 80 mg daily dosage who require therapy with an interacting drug (i.e., a drug with which concomitant use is contraindicated or is associated with a dose limit for simvastatin), switch to alternative statin or statin-based regimen with less drug interaction potential.20
Special Populations
Hepatic Impairment
Ezetimibe
Mild hepatic impairment: No dosage adjustment needed.1
Moderate or severe hepatic impairment: Do not use.1
Renal Impairment
Ezetimibe
No dosage adjustment needed in patients with renal impairment.1
Ezetimibe/Simvastatin Fixed Combination
Mild renal impairment (estimated GFR ≥60 mL/minute per 1.73 m2): No dosage adjustment needed.20
Chronic kidney disease and estimated GFR <60 mL/minute per 1.73 m2: Ezetimibe 10 mg/simvastatin 20 mg once daily; use higher dosages with caution and close monitoring.1 20 (See Renal Impairment under Cautions.)
Geriatric Patients
Ezetimibe
No dosage adjustment needed in geriatric patients (≥65 years of age).1
Ezetimibe/Simvastatin Fixed Combination
No dosage adjustment needed in geriatric patients (≥65 years of age).12
Cautions for Ezetimibe
Contraindications
-
Known hypersensitivity to ezetimibe or any ingredient in the formulation.1
-
Fixed combination of ezetimibe and simvastatin: Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase (transaminase) concentrations; in pregnant or nursing women; or in patients receiving concomitant therapy with potent inhibitors of CYP3A4, cyclosporine, danazol, or gemfibrozil.20
Warnings/Precautions
Sensitivity Reactions
Hypersensitivity Reactions
Anaphylaxis, angioedema, rash, and urticaria reported.1 12
Major Toxicities
Hepatic Effects
Transient elevations in serum aminotransferase (AST, ALT) concentrations3 4 >3 times the ULN reported.1 12 Elevations reported more frequently with ezetimibe-statin combination than with statin monotherapy.1 Hepatitis reported; however, causal relationship not established.1 12
ACC/AHA cholesterol management guideline states it is reasonable to obtain baseline hepatic aminotransferase concentrations before initiating ezetimibe.350 When used with a statin, perform liver function tests at initiation of therapy and in accordance with the recommended monitoring schedule for the specific statin and as clinically indicated.1 350 If ALT or AST concentrations increase to ≥3 times the ULN and are persistent, consider discontinuing ezetimibe and/or the statin.1
Musculoskeletal Effects
Marked (>10 times ULN) elevations of CK (CPK) reported.1 Elevations in CK concentrations reported more frequently with ezetimibe-statin combination than with statin monotherapy.1
Myalgia, myopathy (i.e., unexplained muscle pain, tenderness, or weakness and CK concentration >10 times ULN), and/or rhabdomyolysis reported.1 12 Most cases of rhabdomyolysis occurred in patients receiving statin therapy prior to initiating ezetimibe; however, rhabdomyolysis also reported following ezetimibe monotherapy or following addition of ezetimibe to therapy with agents known to be associated with increased risk of rhabdomyolysis (e.g., fibric acid derivatives).1 20
Predisposing factors for the development of myopathy and/or rhabdomyolysis include increased dosages of statins, age >65 years, uncontrolled hypothyroidism, renal impairment, and potential statin-drug interactions.1 20 Immediately discontinue ezetimibe and any concomitant statin or fibric acid derivative (e.g., gemfibrozil, fenofibrate) if myopathy is diagnosed or suspected.1 12
General Precautions
Combination Therapy with Statins or Fenofibrate
When used in combination or fixed combination with a statin or fenofibrate, consult prescribing information of specific statin or fenofibrate for detailed information on usual cautions, precautions, and contraindications of these drugs.1 12
Risk of Cancer
Findings from the SEAS study suggested a possible increased risk of cancer with use of the fixed combination of simvastatin and ezetimibe.15 17 The results of 2 large-scale randomized trials (SHARP and IMPROVE-IT) found no such association.307 308 309 FDA concluded that ezetimibe and the fixed-combination preparation of ezetimibe and simvastatin is not likely to increase the risk of cancer or cancer-related deaths.307
Specific Populations
Pregnancy
Category C.1
Fixed combination of ezetimibe and simvastatin: Category X (due to simvastatin component).20
Lactation
Distributed into milk in rats; not known whether distributed into human milk.1 Use with caution in nursing women; not recommended unless potential benefits justify possible risks to infant.1
Pediatric Use
Safety and efficacy not established in children <10 years of age; use not recommended in these children.1
Safety and efficacy of ezetimibe alone or in fixed combination with simvastatin not established in prepubertal girls or in children ≤10 years of age.1 20
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 20
Use fixed combination of ezetimibe and simvastatin with caution, since age ≥65 years is a risk factor for myopathy, including rhabdomyolysis.20
Hepatic Impairment
Safety of increased exposure to ezetimibe in patients with moderate or severe hepatic impairment currently not known; use not recommended in such patients.1
Renal Impairment
In patients with moderate to severe renal impairment receiving ezetimibe 10 mg/simvastatin 20 mg in fixed combination, incidence of certain adverse effects (serious effects; those resulting in drug discontinuance; musculoskeletal effects, liver enzyme abnormalities, or incident cancer) was similar to that with placebo.1 20 Use higher dosages with caution and close monitoring in such patients, since renal impairment increases risk for myopathy.1 20 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Ezetimibe monotherapy: Upper respiratory tract infection,1 diarrhea,1 3 arthralgia,1 2 sinusitis,1 pain in extremity,1 fatigue,1 influenza.1
Ezetimibe in combination with a statin: Nasopharyngitis,1 myalgia,1 20 upper respiratory tract infection,1 2 4 20 arthralgia,1 headache,20 diarrhea,1 20 back pain,1 influenza,1 20 pain in extremity.1 20
Adverse effects associated with combination therapy generally similar to those reported with monotherapy.1 However, elevations in transaminase concentrations reported more frequently with ezetimibe-statin combination than with statin monotherapy.1
Interactions for Ezetimibe
Does not inhibit or induce CYP1A2, 2D6, 2C8, 2C9, or 3A4.1 Pharmacokinetic interactions with drugs metabolized by these isoenzymes (e.g., caffeine, dextromethorphan, tolbutamide, IV midazolam) unlikely.1
When used in fixed combination with simvastatin, consider drug interactions associated with simvastatin.12 No formal drug interaction studies to date with fixed-combination preparation other than that with extended-release niacin.20 (See Specific Drugs under Interactions.)
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Antacids, aluminum and magnesium hydroxides-containing |
Decreased ezetimibe peak plasma concentrations but no effect on AUC1 |
|
Bile acid sequestrants (cholestyramine) |
Decreased ezetimibe AUC but no effect on peak plasma concentration; may result in reduced LDL-lowering effect1 |
Administer ezetimibe ≥2 hours before or ≥4 hours after bile acid sequestrant1 |
Caffeine |
Pharmacokinetic interaction unlikely1 |
|
Cimetidine |
Increased ezetimibe peak plasma concentration but no effect on AUC1 |
|
Cyclosporine |
Increased ezetimibe and cyclosporine concentrations; possible greater ezetimibe exposure in patients with severe renal impairment 1 12 |
Use concomitantly with caution;1 monitor cyclosporine concentrations with concomitant use1 |
Dextromethorphan |
Pharmacokinetic interaction unlikely1 |
|
Digoxin |
No substantial effect on peak plasma concentrations and AUC of digoxin1 |
|
Fat-soluble vitamins |
Pharmacokinetic interaction with vitamins A, D, and E unlikely1 8 |
|
Fibric acid derivatives (fenofibrate, gemfibrozil) |
Fenofibrate, gemfibrozil: Increased AUC and peak plasma concentrations of ezetimibe; no effect on exposure to the fibric acid derivative1 Ezetimibe associated with increased cholesterol excretion in gall bladder bile;1 fibric acid derivatives may increase cholesterol excretion in bile, leading to cholelithiasis1 Cholecystectomy reported1 Very rare postmarketing reports of myopathy/rhabdomyolysis with concomitant use1 |
Fenofibrate: If cholelithiasis is suspected, perform gallbladder studies and consider alternative antilipemic therapy1 Concomitant use with a fibric acid derivative other than fenofibrate currently not recommended1 (see Musculoskeletal Effects under Cautions) |
Glipizide |
No effect on ezetimibe or glipizide exposure1 |
|
HMG-CoA reductase inhibitors (statins) (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin) |
Pharmacokinetic interaction unlikely1 3 5 Rare postmarketing reports of myopathy/rhabdomyolysis with concomitant use1 |
Monitor liver function according to recommendations for statin with concomitant use1 Discontinue ezetimibe and any concomitant statin if myopathy diagnosed or suspected1 (see Musculoskeletal Effects under Cautions) |
Midazolam (IV) |
Pharmacokinetic interaction unlikely1 |
|
Mipomersen |
No clinically relevant pharmacokinetic interactions observed375 |
No dosage adjustment of ezetimibe or mipomersen required375 |
Niacin (antilipemic dosages [≥1 g daily]) |
Extended-release niacin (Niaspan) with fixed combination of ezetimibe and simvastatin: Increased peak plasma concentrations and AUC of niacin and nicotinuric acid; increased peak plasma concentrations of simvastatin acid; increased AUC of total ezetimibe, simvastatin, and simvastatin acid20 |
Weigh benefits against risks of concomitant therapy with ezetimibe-simvastatin fixed combination; use concomitantly with caution20 Patients of Chinese descent: Caution when used concomitantly with fixed-combination preparation containing dosages exceeding ezetimibe 10 mg/simvastatin 20 mg daily; avoid concomitant use with ezetimibe 10 mg/simvastatin 80 mg daily20 |
Oral contraceptives, ethinyl estradiol- and levonorgestrel-containing |
No effect on ethinyl estradiol or levonorgestrel exposure1 |
|
Tolbutamide |
Pharmacokinetic interaction unlikely1 |
|
Warfarin |
Pharmacokinetic and pharmacologic interaction unlikely based on one study;1 8 12 no effect on R- or S-warfarin exposure1 Increased INR with combined ezetimibe-warfarin therapy reported during postmarketing experience; most patients also on other drugs1 12 |
Monitor INR appropriately if ezetimibe is initiated in a patient receiving warfarin1 |
Ezetimibe Pharmacokinetics
Absorption
Bioavailability
Approximately 93% of dose is absorbed systemically following oral administration.1
Absolute bioavailability cannot be determined because ezetimibe is virtually insoluble in aqueous media suitable for injection.1 Ezetimibe/simvastatin fixed-combination preparation is bioequivalent to corresponding dosages of the individual components.12
Peak plasma concentrations attained within 4–12 hours following oral administration.1
Onset
Maximal or near-maximal reductions in serum lipoprotein and apolipoprotein concentrations achieved within 2 weeks.1 2 8
Duration
Reductions in serum lipoprotein and apolipoprotein concentrations maintained during continued therapy.1 2 8
Food
Food (high-fat or nonfat meals) does not affect extent of absorption.1 High-fat meals associated with increased peak plasma concentrations.1
Special Populations
Increased plasma concentrations in geriatric individuals (≥65 years of age), in patients with hepatic impairment, and in patients with severe renal impairment.1 (See Special Populations under Dosage and Administration.)
No differences in pharmacokinetic parameters between blacks and Caucasians.1 Studies in Asian individuals indicated similar pharmacokinetics as observed in Caucasian individuals.1
Distribution
Plasma Protein Binding
>90%.1
Elimination
Metabolism
Rapidly metabolized principally in small intestine and liver to ezetimibe glucuronide (active).1 Ezetimibe and ezetimibe glucuronide constitute approximately 10–20% and 80–90%, respectively, of total drug in plasma.1
Possible enterohepatic recycling.1
Elimination Route
Excreted in feces (78%) and urine (11%) within 10 days after dosing.1 Major component in feces is ezetimibe (69% of administered dose); major component in urine is ezetimibe glucuronide (9% of administered dose).1
Half-life
Approximately 22 hours for both ezetimibe and ezetimibe glucuronide.1
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).1 Protect from moisture.1
Ezetimibe/simvastatin fixed-combination preparation: Well-closed containers at 20–25°C.20 When subdividing contents of a large-quantity container, repackage into tightly closed, light-resistant containers; entire contents must be repackaged immediately upon opening.20
Actions
-
Localizes at brush border of small intestine and inhibits absorption of cholesterol,3 4 8 resulting in decreased delivery of intestinal cholesterol to liver.1 Intestinal absorption of cholesterol reduced by approximately 54% in a limited number of patients with hypercholesterolemia.1 6
-
Has been shown to reduce concentrations of noncholesterol sterols,8 including sitosterol and campesterol.1 6
-
Does not appear to inhibit hepatic cholesterol synthesis or increase bile acid excretion.1 Does not appear to inhibit absorption of triglycerides, fatty acids, bile acids, progesterone, or ethyl estradiol.1 No clinically relevant effects on plasma concentrations of fat-soluble vitamins A, D, and E;8 does not appear to impair adrenocortical steroid production.1
-
Cholesterol-lowering effects of ezetimibe and statins or of ezetimibe and fenofibrate are additive.1
Advice to Patients
-
Importance of adherence to prescribed directions for use, particularly when used concomitantly with other antilipemic agents.1 12
-
Importance of adherence to a standard cholesterol-lowering diet.1 8 20
-
Risk of myopathy and/or rhabdomyolysis; risk increased when used concomitantly with certain other drugs or grapefruit juice.1 20 Importance of promptly informing clinicians of unexplained muscle pain, weakness, or tenderness, particularly if accompanied by malaise or fever or if such manifestations persist after discontinuance of therapy.1 20
-
Risk of adverse hepatic effects.1 20 Importance of monitoring liver function tests at initiation of ezetimibe if used in combination with a statin and thereafter in accordance with the recommendation of the statin.1 20 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) when ezetimibe is used in combination simvastatin.20
-
Importance of women informing their clinician if they are or plan to become pregnant.1 20 Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) and informing pregnant women of risk to fetus when using ezetimibe in combination with statin therapy.1 20
-
Importance of avoiding breast-feeding when using ezetimibe in combination with statin therapy.1 20 If the patient has a lipid disorder and is breast-feeding, importance of contacting a clinician to discuss other antilipemic treatment options.1 20
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 12
-
Importance of informing patients of other important precautionary information.1 12 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
10 mg* |
Ezetimibe Tablets |
|
Zetia |
Merck/Schering-Plough |
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets |
10 mg with Simvastatin 10 mg |
Vytorin |
Merck |
10 mg with Simvastatin 20 mg |
Vytorin |
Merck |
||
10 mg with Simvastatin 40 mg |
Vytorin |
Merck |
||
10 mg with Simvastatin 80 mg |
Vytorin |
Merck |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 26, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
1. Merck & Co., Inc. Zetia (ezetimibe) tablets prescribing information. Whitehouse Station, NJ; 2013 Aug.
2. Dujovne CA, Ettinger MP, McNeer JF et al for the Ezetimibe Study Group. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002; 90:1092-7. http://www.ncbi.nlm.nih.gov/pubmed/12423709?dopt=AbstractPlus
3. Gagne C, Bays HE, Weiss SR et al for the Ezetimibe Study Group. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002; 90:1084-91. http://www.ncbi.nlm.nih.gov/pubmed/12423708?dopt=AbstractPlus
4. Gagne C, Gaudet D, and Bruckert E for the Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002; 105:2469-75. http://www.ncbi.nlm.nih.gov/pubmed/12034651?dopt=AbstractPlus
5. Kosoglou T, Meyer I, Veltri EP et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol. 2002; 54:309-19. http://www.ncbi.nlm.nih.gov/pubmed/12236852?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1874429&blobtype=pdf
6. Sudhop T, Lutjohann D, Kodal A et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002; 106:1943-8. http://www.ncbi.nlm.nih.gov/pubmed/12370217?dopt=AbstractPlus
7. Ezzet F, Krishna G, Wexler DB et al. A population pharmacokinetic model that describes multiple peaks due to enterohepatic recirculation of ezetimibe. Clin Ther. 2001; 23:871-85. http://www.ncbi.nlm.nih.gov/pubmed/11440287?dopt=AbstractPlus
8. Merck/Schering-Plough, PA: Personal communication.
9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-23.
10. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Bethesda, MD: National Institutes of Health. (NIH publication No. 01-3670.)
11. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm
12. Merck/Schering-Plough. Vytorin (ezetimibe and simvastatin) tablets prescribing information. North Wales, PA; Nov 05.
13. Ballantyne CM, Houri J, Notarbartolo A et al for the Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003; 107:2409-15. http://www.ncbi.nlm.nih.gov/pubmed/12719279?dopt=AbstractPlus
14. Food and Drug Administration. Vytorin (ezetimibe and simvastatin) tablets [Undated: Merck/Schering-Plough Pharmaceuticals]. Rockville, MD; FDA Action Date October 24, 2006. From Drugs@FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2006/021687s010ltr.pdf
15. Rossebø AB, Pedersen TR, Boman K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008; 359:1343-56. http://www.ncbi.nlm.nih.gov/pubmed/18765433?dopt=AbstractPlus
16. Peto R, Emberson J, Landray M et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008; 359:1357-66. http://www.ncbi.nlm.nih.gov/pubmed/18765432?dopt=AbstractPlus
17. Food and Drug Administration. Early communication about an ongoing safety review of ezetimibe/simvastatin (marketed as Vytorin), simvastatin (marketed as Zocor) and ezetimibe (marketed as Zetia): FDA investigates a report from the SEAS trial. Rockville, MD; 2008 Aug 21. Available from FDA website. Accessed 2008 Oct 9. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm162899.htm
18. Food and Drug Administration. Follow-up to the January 25, 2008 early communication about an ongoing data review for ezetimibe/simvastatin (marketed as Vytorin), ezetimibe (marketed as Zetia), and simvastatin (marketed as Zocor). Rockville, MD; 2009 Jan 8. Available from FDA website. Accessed 2009 Sep 10. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079524.htm
20. Merck & Co., Inc. Vytorin (ezetimibe and simvastatin) tablets prescribing information. Whitehouse Station, NJ; 2016 Oct.
307. Food and Drug Administration. Follow-Up to the August 2008 Early Communication About an Ongoing Safety Review of Ezetimibe/Simvastatin (marketed as Vytorin), Simvastatin (marketed as Zocor) and Ezetimibe (marketed as Zetia) - FDA Investigates a Report from the SEAS Trial. Rockville, MD; 2009 Dec 22. Available from FDA website. Accessed 2008 Oct 9. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm194964.htm
308. 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; 377:2181-92. http://www.ncbi.nlm.nih.gov/pubmed/21663949?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3145073&blobtype=pdf
309. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015; 372:2387-97. http://www.ncbi.nlm.nih.gov/pubmed/26039521?dopt=AbstractPlus
310. Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf. 2010; 9:603-21. http://www.ncbi.nlm.nih.gov/pubmed/20377474?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2910322&blobtype=pdf
350. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; :. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a
352. Eckel RH, Jakicic JM, Ard JD et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63:2960-84. http://www.ncbi.nlm.nih.gov/pubmed/24239922?dopt=AbstractPlus
375. Genzyme Corporation. Kynamro (mipomersen sodium) injection solution for subcutaneous injection prescribing information. Cambridge, MA; 2013 Jan.
Frequently asked questions
- Can it cause weight gain or loss?
- What happens if you stop taking it?
- Does it lower triglycerides?
- When is the best time to take it?
- When should you take it?
- When is the best time to take it?
- Is it a statin drug?
- Can it be used with statin drugs?
More about ezetimibe
- Side Effects
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Images
- Drug Interactions
- Compare Alternatives
- Pricing & Coupons
- En Español
- 115 Reviews
- Drug class: cholesterol absorption inhibitors
- FDA Alerts (2)
Consumer resources
Professional resources
- Other brands
- Zetia