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Ezetimibe is a drug that lowers plasma cholesterol levels. It acts by decreasing cholesterol absorption in the small intestine. It may be used alone (marketed as Zetia or Ezetrol ), when other cholesterol-lowering medications are not tolerated, or together with statins (e.g., ezetimibe/simvastatin, marketed as Vytorin or Inegy ) when statins alone do not control cholesterol.
Ezetimibe is recommended as second line therapy for those intolerant of statins or unable to achieve target low-density lipoprotein (LDL) cholesterol levels on statins alone by several major medical group practice guidelines, including the American College of Cardiology. In the United States as of 2015 the 10 mg pill costs between 4.84 and 7.88 USD.
1 Medical uses
3 Adverse effects
5 Mechanism of action
7 See also
As of mid-2014, treatment guidelines of the American Heart Association /American College of Cardiology recommend ezetimibe as one of several second line treatment options for people who are intolerant of statins or who are unable to reach serum LDL goals using statins alone.
While ezetimibe reduces LDL cholesterol, it has not been shown to affect outcomes such as risk of death or major cardiovascular event like heart attack or stroke.
Ezetimibe is indicated in the United States as an add-on to dietary measures to:
reduce levels of certain lipids in people with primary hyperlipidemia, alone or with a statin ;
reduce levels of certain lipids in people with mixed hyperlipidemia, in combination with fenofibrate ;
reduce levels of certain lipids in people with homozygous familial hypercholesterolemia, in combination with specific statins;
reduce levels of certain lipids in people with homozygous sitosterolemia.
The two contraindications to taking ezetimibe are a previous allergic reaction to ezetimibe, including symptoms of rash, angioedema, and anaphylaxis, and severe liver disease, especially when taken with a statin.
Ezetimibe may have significant medication interactions with cyclosporine and with fibrates other than fenofibrate.
Common adverse drug reactions (≥1% of patients) associated with ezetimibe therapy include: headache and/or diarrhea (steatorrhea). Infrequent adverse effects (0.1–1% of patients) include: myalgia and/or raised liver function test ( ALT / AST ) results. Rarely (<0.1% of patients), hypersensitivity reactions (rash, angioedema ) or myopathy may occur. Overdose The incidence of overdose with ezetimibe is rare; there is subsequently little data on the effects of overdose. However, an acute overdose of ezetimibe is expected to produce an exaggeration of its usual effects, leading to loose stools, abdominal pain, and fatigue. Mechanism of action Ezetimibe inhibits the absorption of cholesterol from the small intestine and decreases the amount of cholesterol normally available to liver cells, leading them to absorb more from circulation and thus lowering levels of circulating cholesterol. The exact mechanism is not known, but it appears that ezetimibe blocks the critical mediator of cholesterol absorption, the Niemann-Pick C1-like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes ; blocks aminopeptidase N, and interrupts a Caveolin 1 - Annexin A2 complex involved in trafficking cholesterol. Pharmacokinetics Within 4–12 hours of the oral administration of a 10 mg dose to fasting adults, the attained mean ezetimibe peak plasma concentration ( C max ) was 3.4–5.5 ng/ml. Following oral administration, ezetimibe is absorbed and extensively conjugated to a phenolic glucuronide (active metabolite). Mean C max (45–71 ng/ml) of ezetimibe-glucuronide is attained within 1–2 h. The concomitant administration of food (high-fat vs. nonfat meals) has no effect on the extent of absorption of ezetimibe. However, coadministration with a high-fat meal increases the C max of ezetimibe by 38%. The absolute bioavailability cannot be determined, since ezetimibe is insoluble in aqueous media suitable for injection. Ezetimibe and its active metabolite are highly bound to human plasma proteins (90%). Ezetimibe is primarily metabolized in the liver and the small intestine via glucuronide conjugation with subsequent renal and biliary excretion. See also Cholesterol absorption inhibitor Ezetimibe/simvastatin Ezetimibe/atorvastatin Niacin SCH-48461 NPC1L1
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