How does ezetimibe reduce blood cholesterol?
Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. In a 2-week clinical study in 18 hypercholesterolemic patients, Ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo.
What is the role of ezetimibe in the treatment of FH?
Ezetimibe inhibits intestinal cholesterol absorption and is effective in lowering cholesterol as monotherapy or in combination with statins in several populations, including those with FH, sitosterolemia, and insulin resistance.
What are the side effects of ezetimibe?
Serious side effects may include anaphylaxis, liver problems, depression, and muscle breakdown. Use in pregnancy and breastfeeding is of unclear safety. Ezetimibe works by decreasing cholesterol absorption in the intestines.
How is ezetimibe administered?
Ezetimibe can be administered with or without food. Ezetimibe and Ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins. Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation (a phase II reaction) with subsequent biliary and renal excretion.
How does ezetimibe work in the body?
How does it work? Ezetimibe works by reducing the amount of cholesterol your body takes in from your food. It is usually prescribed alongside a cholesterol-lowering diet. Ezetimibe can often be prescribed together with a statin to further lower your cholesterol levels.
How is ezetimibe different from a statin?
Ezetimibe inhibits cholesterol absorption in the intestine whereas statins inhibit cholesterol production primarily in the liver; so they have complementary effects.
What enzyme does ezetimibe inhibit?
NPC1L1 transport proteinsAbstract. Ezetimibe is the first agent used in hypercholesterolemia treatment known to lower intestinal cholesterol uptake that is able to inhibit NPC1L1 transport proteins in the brush boarder of enterocytes and macrophages.
What is the mechanism of action of the cholesterol absorption inhibitor?
Mechanism of action: Normally, transporters exist in the GI tract to facilitate the absorption of cholesterol from digested foods. Ezetimibe inhibits a transporter involved in this process, which causes a decrease in the amount of cholesterol absorbed.
What foods should be avoided when taking ezetimibe?
Grapefruit Juice: Ezetimibe interacts with grapefruit juice. Grapefruit juice increases the drug levels in the blood stream potentially leading to side effects of the drug.
What drugs should not be taken with ezetimibe?
Serious interactions of ezetimibe include: cyclosporine....What Other Drugs Interact with Ezetimibe?fenofibrate.fenofibrate micronized.fenofibric acid.gemfibrozil.
Can you take ezetimibe without a statin?
Ezetimibe comes as a tablet which you take once a day at a dose of 10mg. It might be combined with a statin or you might be prescribed it on it's own if you can't take statins.
When is the best time to take ezetimibe?
There is no specific time of the day that is best to take ezetimibe, as it works exactly the same whether you take in the morning, afternoon or at night. Ezetimibe is taken once a day, at the same time each day and it can be taken with or without food.
Is ezetimibe better than statins?
Ezetimibe: Safety and Efficacy Ezetimibe lowers low-density lipoprotein cholesterol (LDL-C) by 15-20% when used alone2 as compared to 5-10% from doubling the dose of statin.
Does ezetimibe cause memory loss?
Official answer. Memory loss is not a side effect of Zetia (ezetimibe) when it is used alone to treat high cholesterol. Zetia is often used with other cholesterol lowering medications like statins which have been linked with cognitive impairment (memory loss, forgetfulness, or confusion).
When do you add ezetimibe to statins?
In patients admitted with an acute coronary syndrome and low-density lipoprotein cholesterol ≥50 mg/dL, healthcare providers should consider adding ezetimibe to statin to reduce the risk of cardiovascular events.
How long does it take to get ezetimibe out of your system?
Most of a Zetia dose is removed from your body within 22 hours. It may take up to 5 days for the drug to be completely removed from your system. If you have more questions about how Zetia works or how long it stays in your body, talk with your doctor or pharmacist.
Is ezetimibe better than statins?
Ezetimibe: Safety and Efficacy Ezetimibe lowers low-density lipoprotein cholesterol (LDL-C) by 15-20% when used alone2 as compared to 5-10% from doubling the dose of statin.
Can you take ezetimibe without a statin?
Ezetimibe comes as a tablet which you take once a day at a dose of 10mg. It might be combined with a statin or you might be prescribed it on it's own if you can't take statins.
What's the difference between atorvastatin and ezetimibe?
Ezetimibe is a cholesterol absorption inhibitor and atorvastatin is an HMG-CoA reductase inhibitor, or statin. These medicines will reduce the absorption of cholesterol from foods and the production of cholesterol in your body.
Does Zetia have less side effects than statins?
Zetia (ezetimibe) typically has fewer side effects and drug interactions than statins. However, the muscle damage that can occur from taking a statin has also been reported in patients taking Zetia (ezetimibe).
How does ezetimibe work?
Ezetimibe works by decreasing cholesterol absorption in the intestines. Ezetimibe was approved for medical use in the United States in 2002. It is available as a generic medication. In 2018, it was the 125th most commonly prescribed medication in the United States, with more than 5 million prescriptions.
How does ezetimibe affect cholesterol?
Ezetimibe inhibits the absorption of cholesterol from the small intestine and decreases the amount of cholesterol normally available to liver cells. The lower levels of cholesterol in the liver cells leads them to absorb more cholesterol from circulation and thus lowering the levels of circulating cholesterol. It 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; it blocks aminopeptidase N and interrupts a caveolin 1 – annexin A2 complex involved in trafficking cholesterol.
How long does it take for ezetimibe to be absorbed?
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 hours. 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 its C max by 38%. The absolute bioavailability cannot be determined, since ezetimibe is insoluble in aqueous media suitable for injection. Ezetimibe and its active metabolites are highly bound to human plasma proteins (90%).
What is ezetimibe used for?
Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth.
What is the role of NPC1L1 in gastrointestinal tract?
It 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; it blocks aminopeptidase N and interrupts a caveolin 1 – annexin A2 complex involved in trafficking cholesterol.
Where is ezetimibe metabolized?
Ezetimibe is primarily metabolized in the liver and the small intestine via glucuronide conjugation with subsequent renal and biliary excretion. Both the parent compound and its active metabolite are eliminated from plasma with a half-life around 22 hours, allowing for once-daily dosing. Ezetimibe lacks significant inhibitor or inducer effects on cytochrome P450 isoenzymes, which explains its limited number of drug interactions. No dose adjustment is needed in patients with chronic kidney disease or mild hepatic dysfunction (Child-Pugh score 5–6). Due to insufficient data, the manufacturer does not recommend ezetimibe for patients with moderate to severe hepatic impairment (Child-Pugh score 7–15). In patients with mild, moderate, or severe hepatic impairment, the mean AUC values for total ezetimibe are increased about 1.7-fold, 3-to-4-fold, and 5-to-6-fold, respectively, compared to healthy subjects.
What are the adverse events of ezetimibe?
The most commonly reported adverse events include upper respiratory tract infections, joint pain, diarrhea, and tiredness.
What is ezetimibe metabolized to?
In humans, ezetimibe is rapidly and extensively metabolized via a phase II glucuronide conjugation reaction in the small intestine and liver to form its main phenolic metabolite, ezetimibe glucuronide. The main human liver and/or intestinal uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes responsible for the glucuronidation of ezetimibe were shown to be UGT1A1, 1A3, and 2B15 in vitro. 3 Minimal phase I reaction involving oxidation of ezetimibe also occurs to form SCH 57871, and human jejunum microsomes also produced trace levels of a benzylic glucuronide (SCH 488128). 3 Ezetimibe glucuronide accounts for 80-90% of the total circulating compound in plasma, and retains some pharmacological activity in inhibiting intestinal cholesterol uptake. 5 In humans, ezetimibe and ezetimibe-glucuronide constitutes approximately 93% of the total drug in plasma. 5 Plasma concentration-time profiles exhibit multiple peaks, suggestive of enterohepatic recycling 5, and about 20% of the drug distributed is reabsorbed due to enterohepatic recirculation. 10
How does ezetimibe affect cholesterol?
Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients. 3 The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed on enterocytes/gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin. 2 Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPC1L1 and forms a NPC1L1/cholesterol complex. The complex is then internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment. 2
What is ezetimibe used for?
Ezetimibe is a cholesterol absorption inhibitor used to lower total cholesterol, LDL-C, Apo-B, and non-HDL-C in primary hyperlipidemia and familial cholesterolemia. Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterol absorption.
How long does ezetimibe last?
Both ezetimibe and ezetimibe-glucuronide display an approximate half-life of 22 hours. 5
How long does it take for ezetimibe to work?
Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in peak plasma concentrations (C max) of 3.4-5.5 ng/mL within 4-12 hours (T max ). 5 The C max of the major pharmacologically-active metabolite, ezetimibe-glucuronide, was 45-71 ng/mL and its T max was 1-2 hours. 5 Food consumption has minimal effect on ezetimibe absorption, but the C max is increased by 38% when administered alongside a high-fat meal. 5 The true bioavailability of ezetimibe cannot be determined, as it is insoluble in aqueous media suitable for intravenous injection. 5
What is the relative volume of distribution of ezetimibe?
The relative volume of distribution of ezetimibe is 107.5L. 10
Does ezetimibe have a lower absorption rate?
Cholesterol. Cholesterol may increase the excretion rate of Ezetimibe which could result in a lower serum level and potentially a reduction in efficacy. Cholestyramine. Cholestyramine can cause a decrease in the absorption of Ezetimibe resulting in a reduced serum concentration and potentially a decrease in efficacy.
What is ezetimibe used for?
Ezetimibe tablets are indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.
What is the chemical formula for ezetimibe?
The chemical name of Ezetimibe is 1- (4-fluorophenyl)-3 (R)- [3- (4-fluorophenyl)-3 (S)-hydroxypropyl]-4 (S)- (4-hydroxyphenyl)-2-azetidinone. The molecular formula is C 24 H 21 F 2 NO 3. Its molecular weight is 409.4 and its structural formula is:#N#Ezetimibe USP is a white crystalline powder that is freely to very soluble in ethanol, methanol, acetonitrile and acetone and practically insoluble in water. It is also insoluble in non-polar solvents such as hexane. Ezetimibe has a melting point of about 163°C and is stable at ambient temperature. Ezetimibe tablets USP is available as a tablet for oral administration containing 10 mg of Ezetimibe and the following inactive ingredients: croscarmellose sodium, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate.#N#Meets USP Dissolution Test 2.
What is the combination of Ezetimibe and atorvastatin?
The combination of Ezetimibe tablets and atorvastatin or simvastatin is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
What is the name of the tablet with K 31 on the side?
Ezetimibe tablets USP, 10 mg are white to off-white, capsule shaped beveled edge tablets debossed with "K 31" on one side and plain on other side.
What is the ED 50 of Ezetimibe?
Ezetimibe was found to have an ED 50 value of 0.5 mcg/kg/day for inhibiting the rise in plasma cholesterol levels in monkeys. The ED 50 values in dogs, rats, and mice were 7, 30, and 700 mcg/kg/day, respectively. These results are consistent with Ezetimibe being a potent cholesterol absorption inhibitor.
How old are you when you get Ezetimibe?
Of the 2396 patients who received Ezetimibe in clinical studies, 669 (28%) were 65 and older, and 111 (5%) were 75 and older.
Does ezetimibe cause rhabdomyolysis?
Most patients who developed rhabdomyolysis were taking a statin prior to initiating Ezetimibe. However, rhabdomyolysis has been reported with Ezetimibe monotherapy and with the addition of Ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibrates.
When to discontinue ezetimibe?
Hepatic transaminase levels: Baseline LFTs (reasonable); when used in combination with statin therapy, monitor LFTs when clinically indicated; discontinue use of ezetimibe if ALT elevations >3 times upper limit of normal persist. When used in combination with fenofibrate, monitor LFTs and signs and symptoms of cholelithiasis.
Does Niemann pick C1-Like1 increase cholesterol?
Inhibits absorption of cholesterol at the brush border of the small intestine via the sterol transporter, Niemann-Pick C1-Like1 (NPC1L1). This leads to a decreased delivery of cholesterol to the liver, reduction of hepatic cholesterol stores and an increased clearance of cholesterol from the blood; decreases total C, LDL-cholesterol (LDL-C), ApoB, and triglycerides (TG) while increasing HDL-cholesterol (HDL-C).
Does ezetimibe cause elevated transaminases?
Elevated hepatic transaminases: A higher incidence of elevated transaminases (≥3 x ULN) has been observed with concomitant use of ezetimibe and statins compared to statin monotherapy; transaminase changes were generally not associated with symptoms or cholestasis and returned to baseline with or without discontinuation of therapy. Consider discontinuation of ezetimibe and/or the statin for persistently elevated transaminases (ALT or AST ≥3 x ULN).
Does fenofibrate affect ezetimibe?
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Monitor therapy
Can you use ezetimibe with severe renal impairment?
Renal impairment: Use with caution in patients with severe renal impairment (CrCl ≤30 mL/minute/1.73 m 2 ); systemic exposure is increased ~1.5-fold. If using concurrent simvastatin in patients with moderate to severe renal impairment (CrCl <60 mL/minute/1.73m 2 ), the manufacturer of ezetimibe recommends that simvastatin doses exceeding 20 mg be used with caution and close monitoring for adverse events (eg, myopathy).
Is bezafibrate a toxic drug?
Bezafibrate: May enhance the adverse/toxic effect of Ezetimibe. Specifically, the risk of myopathy and cholelithiasis may be increased. Avoid combination
Is systemic exposure increased in hepatic impairment?
Hepatic impairment: Systemic exposure is increased in hepatic impairment. Use with caution in patients with mild hepatic impairment (Child-Pugh class A); use is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh classes B and C).
Overview
Pharmacology
Ezetimibe inhibits the absorption of cholesterol from the small intestine and decreases the amount of cholesterol normally available to liver cells. The lower levels of cholesterol in the liver cells leads them to absorb more cholesterol from circulation and thus lowering the levels of circulating cholesterol. It 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; it blocks a…
Medical uses
A 2015 review found that adding ezetimibe to statin treatment of high blood cholesterol had no effect on overall mortality or cardiovascular mortality, although it significantly reduced the risk of myocardial infarction and stroke. A 2015 trial found that adding ezetimibe to simvastatin had no effect on overall mortality but did lower the risk of heart attack or stroke in people with prior heart attack. Several treatment guidelines recommend adding ezetimibe in select high risk persons in …
Contraindications
The two contraindications to taking ezetimibe are a previous allergic reaction to it, including symptoms of rash, angioedema, and anaphylaxis, and severe liver disease, especially when taken with a statin.
Ezetimibe may have significant medication interactions with ciclosporin and with fibrates other than fenofibrate.
Adverse effects
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. Cases of muscle problems (myalgia and rhabdomyolysis) have been reported and are included as warnings on the label for e…
Overdose
The incidence of overdose with ezetimibe is rare; subsequently, few data exist 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.
External links
• "Ezetimibe". Drug Information Portal. U.S. National Library of Medicine.