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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: ezetimibe (eh ZET i meeb)
Brand name(s): ZETIA
GENERIC: not available FAMILY: Other Drugs for High Cholesterol
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: ezetimibe with simvastatin
Brand name(s):
GENERIC: not available
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

Ezetimibe crossed the placenta and caused an increase in misshapen skeletons in animal studies. Because of the potential for serious adverse effects to the fetus, ezetimibe should not be used by pregnant women.

Breast-feeding Warning

Ezetimibe is excreted in animal milk. It is likely that this drug, like many others, is also excreted in human milk and, because of the potential for serious adverse effects in nursing infants, you should not take ezetimibe while nursing.

Facts About This Drug [top]

Ezetimibe (ZETIA) is a drug that lowers cholesterol. It is approved to treat high cholesterol due to high low-density lipoprotein cholesterol (LDL-C, "bad" cholesterol), caused by heredity or due to high blood levels of sitosterol and campesterol.[1] Ezetimibe belongs to a family of drugs called azetidinones. Ezetimibe works by partially blocking the absorption of cholesterol in the small intestine.[2]

Although ezetimibe lowers cholesterol levels, there is no evidence that it reduces the...

Ezetimibe (ZETIA) is a drug that lowers cholesterol. It is approved to treat high cholesterol due to high low-density lipoprotein cholesterol (LDL-C, "bad" cholesterol), caused by heredity or due to high blood levels of sitosterol and campesterol.[1] Ezetimibe belongs to a family of drugs called azetidinones. Ezetimibe works by partially blocking the absorption of cholesterol in the small intestine.[2]

Although ezetimibe lowers cholesterol levels, there is no evidence that it reduces the risk of heart attacks or strokes. The principal marketing claim for ezetimibe has been its improved safety over other cholesterol-lowering drugs, particularly the statins. However, there is no actual proof that it is, in fact, any safer.[3]

Patients with moderate to severe liver disease should not use ezetimibe.[4] Unlike the statin drugs, ezetimibe does not lower production of cholesterol by the liver. In fact, the liver may compensate by increasing cholesterol production, although overall LDL declines.

Ezetimibe should not be used with fibric acid drugs such as gemfibrozil (LOPID) and fenofibrate (TRICOR).

Patients who take ezetimibe with other cholesterol-lowering drugs should be aware that these drugs also have contraindications, warnings and side effects that must be considered in addition to ones for ezetimibe.

All cholesterol-lowering drugs are intended to be part of a therapy that also includes exercise and a diet low in saturated fat and cholesterol. Drugs should be prescribed only after diet and exercise alone prove inadequate.

An article in Prescire International in 2010 stated that in 2009 the French Transparency Committee (a committee that assesses the comparative effectiveness of new drugs) lowered its rating of ezetimibe for the treatment of primary hypercholesterolaemia from moderate to minor. The change in rating was based on the absence of available clinical data to fully assess the use of ezetimibe for this diagnosis.[5]

Side effects

Ezetimibe seems to share psychiatric risks with other cholesterol-lowering drugs. There have been reports of aggressive behavior: memory impairment; mood changes; and cognitive, sleep and perception disorders (such as nightmares) associated with the use of many drugs used to treat high cholesterol: ezetimibe, fenofibrate (TRICOR)gemfibrozil (LOPID), clofibrate, and the statin drugs, such as fluvastatin (LESCOL), rosuvastatin (CRESTOR), or simvastatin (ZOCOR).[6],[7]

There also have been reports of depression in users of ezetimibe. Three cases of depressed mood were reported in patients using ezetimibe over a span of three years. In some of these cases, the onset of symptoms was noted within four days of starting the drug.[8]

Though researchers have not yet established a direct link between these reports and the use of the cholesterol-lowering drugs listed, patients should be alert to this possibility and report unexpected changes to their doctor.

Ezetimibe also enhances lowering of cholesterol when used with some other cholesterol-lowering drugs, such as statins.[9],[10],[11],[12] However, adding ezetimibe to statins increases the risk of serious liver adverse events compared with either drug used alone.[13]

Combination of ezetimibe and simvastatin (VYTORIN)

In 2004, the Food and Drug Administration (FDA) approved a pill called VYTORIN which is a combination ezetimibe and simvastatin (ZOCOR). Evidence from the FDA Adverse Events Reports System (AERS) shows that ezetimibe may, on its own, cause rhabdomyolysis (the rapid breakdown of muscle). The FDA reviewer of ezetimibe wrote that:

Pharmacology recommends approval of this drug [ezetimibe] for monotherapy for the proposed indication [use], but preclinical studies do not support safety of ezetimibe in combination with statins [as in VYTORIN]. The toxicity profile appears to be that associated with statins. However the toxicity appears at lower duration and exposure than in statin monotherapy.[14]

The reviewer noted that toxicity seen when ezetimibe was used alone occurred in the heart, lymph nodes, kidneys and bone marrow in laboratory animals; an earlier pharmacology review found lung and liver toxicity as well. When ezetimibe was combined with a statin, toxicity was seen in even more organs: liver, stomach, skeletal muscle, spleen, heart, lungs, testes and prostate.[14]

This finding was given more weight when a 2007 Prescrire International article reviewing the use of the ZOCOR showed an increased risk of side effects with the combination drug ZOCOR than with ezetimibe alone.[15]

The results of a trial completed in April 2006 — but not released until January 14, 2008 — showed that the combination of ezetimibe and simvastatin was of no greater benefit than a statin alone in preventing the buildup of plaque in blood vessels.

There also have been reports linking ezetimibe to triggering muscle and tendon pain when it is added to statin treatment. Unexpected muscle pain can be another early signal for rhabdomyolysis.[16]

Ezetimibe's professional product labeling cautions that when the drug is used in combination with a statin, liver function tests should be performed at the initiation of treatment and according to the recommendations for the statin drug being used. Whether those taking ezetimibe alone also need monitoring is not yet known, but ezetimibe does not appear to cause liver toxicity on its own.[1]

Prescire International published an article in March 2010 concerning the use of ezetimibe and the risk of cancer. The article highlights the results of a clinical trial where, according to the article, patients using ezetimibe (10 mg) with simvastatin versus with placebo showed no clinical cardiovascular benefit. However, cancer was more frequent with ezetimibe (10 mg) and simvastatin versus ezetimibe and placebo. The article also stated that there were more cancer related deaths in the ezetimibe (10 mg) and simvastatin versus ezetimibe with placebo.  Another study, a meta-analysis, found that there was no excess cancer incidence with ezetimibe, however the follow up lasted less than three years.[17]

In 2015, The New England Journal of Medicine published the results of a large randomized study comparing treatment with simvastatin to treatment with both simvastatin and ezetimibe in patients who had a recent heart attack or symptoms similar to a heart attack, known as unstable angina.[18] The study showed that the addition of ezetimibe to simvastatin provided little additional benefit beyond using simvastatin alone.

Before You Use This Drug [top]

Tell your doctor if you have or have had:

  •   allergies
  •   heart problems
  •   liver problems
  •   muscle pain, tenderness, or weakness
  •   pregnancy or are breast-feeding

Tell your doctor about any other drugs you take, including herbs, over-the-counter drugs, progestins, steroids, and vitamins.

When You Use This Drug [top]

  • Eat a diet low in saturated fats and cholesterol, such as the Step 1 diet of the National Cholesterol Education Program. Eat whole grains, legumes, fruits, vegetables, nuts, and fish. Limit cholesterol to 100 milligrams per day, fat to 20% of calories, and saturated fats to 6% of diet. Limit soluble fibers.
  • Exercise regularly.
  • Tell your doctor if you plan to become pregnant.
  • Tell any doctor, dentist, or pharmacist you see that you take this drug.

How to Use This Drug [top]

  • If you miss a dose of ezetimibe, take it as soon as possible, but do not take two doses during the same day. Do not take double doses.
  • Do not share your medication with others.
  • Take the drug at the same time(s) each day.
  • Swallow tablets with or without food.
  • Take ezetimibe at least two hours before or four hours after any bile acid sequestrant.
  • Store tablets at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs [top]

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

Risk of gall bladder disease could increase if ezetimibe is taken with: fenofibrate, fibric acid, gemfibrozil, LOFIBRA, LOPID, TRICOR.

Bile acid sequestrants interfere with absorption of ezetimibe. Take ezetimibe at least two hours before or four hours after: cholestyramine, COLESTID, colestipol, PREVALITE, QUESTRAN, WELCHOL.

If you use ezetimibe with this drug, your doctor should monitor you closely: cyclosporine, SANDIMMUNE.

Adverse Effects [top]

Call your doctor immediately if you experience:

  • large, hive-like swelling on face, lips, eyelids, tongue, throat, hands, legs, feet, sex organs
  • skin rash

Call your doctor if these symptoms continue:

  • dizziness
  • pain in abdomen, back, chest, joints, or stomach
  • muscle pain
  • chest pain
  • trouble breathing
  • trouble swallowing
  • hoarseness
  • dry or sore throat
  • chills or fever
  • cold symptoms, such as congested sinus or runny nose
  • coughing
  • diarrhea
  • fatigue
  • headache

Other adverse effects are possible, especially if you take additional drugs. Check any concerns with your doctor.

Periodic Tests[top]

Ask your doctor which of these tests should be done periodically while you are taking this drug:

  • cholesterol levels (especially LDL and total cholesterol)
  • liver function tests (ALT or AST)

last reviewed April 30, 2021