Zetia (ezetimibe)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ezetimibe, a cholesterol absorption inhibitor, is an antilipemic agent.
Ezetimibe, a cholesterol absorption inhibitor, is an antilipemic agent that differs chemically and pharmacologically from other currently available antilipemic agents. Following absorption, the drug localizes at the brush border of the small intestine and inhibits absorption of cholesterol through the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), resulting in decreased delivery of intestinal cholesterol to the liver. This causes a reduction in hepatic cholesterol stores, a compensatory increase in hepatic uptake of cholesterol from systemic circulation, and consequently, an increase in systemic clearance of cholesterol.
Ezetimibe does not appear to inhibit hepatic cholesterol synthesis or increase bile acid excretion.
Intestinal absorption of cholesterol reportedly was reduced by approximately 54% in a limited number of patients with hypercholesterolemia who received ezetimibe (10 mg daily) for 2 weeks. The cholesterol-lowering effects of ezetimibe and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) or of ezetimibe and fenofibrate are additive. In addition to reducing lipoprotein concentrations, ezetimibe also has been shown to reduce concentrations of noncholesterol sterols, including sitosterol and campesterol.
Ezetimibe does not appear to inhibit the absorption of triglycerides, fatty acids, bile acids, progesterone, or ethinyl estradiol. In 2 separate studies in more than 100 patients each, ezetimibe exhibited no clinically relevant effects on plasma concentrations of fat-soluble vitamins A, D, or E and did not appear to impair adrenocortical steroid production.
Following oral administration, approximately 93% of a radiolabeled dose of ezetimibe is absorbed systemically (as ezetimibe and ezetimibe glucuronide). Food does not appear to affect the extent of absorption of ezetimibe; however, concomitant administration of the drug with a high-fat meal resulted in a 38% increase in peak plasma concentrations of the drug. Following absorption, ezetimibe is rapidly and extensively metabolized in the small intestine and liver to a pharmacologically active phenolic glucuronide metabolite, ezetimibe glucuronide; the drug or its glucuronide metabolite constitutes 10-20 or 80-90%, respectively, of the total absorbed drug in plasma.
Ezetimibe and ezetimibe glucuronide are more than 90% bound to human plasma proteins. The preparation containing ezetimibe in fixed combination with simvastatin is bioequivalent to corresponding dosages of the individual components.
Ezetimibe and ezetimibe glucuronide are each slowly eliminated from plasma with a half-life of approximately 22 hours. Plasma concentration-time profiles of ezetimibe exhibit multiple peaks, suggesting that the drug and its active metabolite may undergo enterohepatic recycling. Following oral administration of 20 mg of 14C-ezetimibe, approximately 78 or 11% of the radioactivity was excreted in feces or urine, respectively, in 10 days; ezetimibe was the major component in feces, while ezetimibe glucuronide was the major component in urine.
Based on a meta-analysis of multiple-dose pharmacokinetic studies, there were no differences in pharmacokinetic parameters between blacks and Caucasians. Studies in Asian individuals indicated that the pharmacokinetics of ezetimibe were similar to those seen in Caucasian individuals.
USES: Ezetimibe is used along with a low cholesterol/low fat diet and exercise to help lower cholesterol in the blood. Ezetimibe may be used alone or with other drugs (such as "statins" or fibrates). Ezetimibe works by reducing the amount of cholesterol your body absorbs from your diet.
Reducing cholesterol may help prevent strokes and heart attacks.
Generic name: ezetimibe
Pronunciation: (eh-ZET-ih-mibe)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Zetia
Indications
The following indications are listed for Zetia:
- Heterozygous Familial Hypercholesterolemia
- Homozygous Familial Hypercholesterolemia
- Hypercholesterolemia
- Hyperlipidemia
- Mixed Hyperlipidemia
- Sitosterolemia
Also known as: Combined Hypercholesterolemia And Hypertriglyceridemia, Elevated Blood Cholesterol Level, Familial Heterozygous Hypercholesterolemia, Familial Homozygous Hypercholesterolemia, Heterozygous Familial Elevated Blood Cholesterol, Hyperlipoidemia, Lipemia, Lipidemia, Lipoidemia, Mixed Dyslipidemia, Phytosterolemia.
Dosing
No dosing information is available for this tab.
Ezetimibe is administered orally without regard to meals. Ezetimibe in fixed combination with simvastatin (e.g., Vytorin(R)) is administered orally in the evening without regard to meals. 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.
When used in combination with a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) or fenofibrate for additive antilipemic effects, ezetimibe may be administered at the same time as the statin or fenofibrate, in accordance with the recommended dosing schedule for these drugs. When used in combination with a bile acid sequestrant, ezetimibe should be administered at least 2 hours before or at least 4 hours after administration of the bile acid sequestrant. The manufacturer states that pending further accumulation of data, use of ezetimibe in combination with a fibric acid derivative other than fenofibrate is not recommended. (See Drug Interactions: Antilipemic Agents.)
Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Adherence to lifestyle modifications for ASCVD risk reduction in addition to statin therapy should be reinforced periodically.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
When using the fixed-combination preparation containing ezetimibe and simvastatin, the drug interactions associated with simvastatin should be considered. No formal drug interaction studies have been performed to date with the fixed-combination preparation other than that with extended-release niacin. (See Niacin under Drug Interactions: Antilipemic Agents.)
When using the fixed-combination preparation containing ezetimibe and bempedoic acid, the drug interactions associated with bempedoic acid should be considered.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to ezetimibe or any ingredient in the formulation.
Ezetimibe, in combination with a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin), is contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase (transaminase) concentrations.
All statins are contraindicated in pregnant or nursing women. If ezetimibe is used in combination with a statin in a woman of childbearing age, the prescribing information for the statin should be consulted for detailed information on contraindications of the drug.
Concomitant use of the fixed combination of ezetimibe and simvastatin with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4, cyclosporine, danazol, or gemfibrozil is contraindicated.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 2% or more of patients receiving ezetimibe and more frequently with the drug than with placebo include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza.
Adverse effects occurring in patients receiving ezetimibe in combination with statins generally were similar to those reported in patients receiving statin therapy alone. However, the incidence of increased transaminase concentrations was higher in patients receiving combination therapy (1.3%) than in those who received statin monotherapy (0.4%). (See Hepatic Effects under Warnings/Precautions: Major Toxicities, in Cautions.) Adverse effects occurring in 2% or more of patients receiving ezetimibe in fixed combination with simvastatin include headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea.
Adverse effects occurring in 2% or more of patients receiving ezetimibe in fixed combination with bempedoic acid include upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, extremity pain, anemia, increased hepatic enzymes, diarrhea, arthralgia, sinusitis, fatigue, and influenza.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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There are no differences in the pharmacokinetics of ezetimibe between adolescents and adults. Pharmacokinetic data are not available for pediatric patients younger than 10 years of age.
Use of ezetimibe in combination with simvastatin has been evaluated in a limited number of adolescent boys and girls with heterozygous familial hypercholesterolemia. In a randomized, double-blind, controlled study in boys and postmenarchal girls 10-17 years of age with heterozygous familial hypercholesterolemia, discontinuance of therapy because of adverse effects occurred in more patients receiving ezetimibe in combination with simvastatin (10-40 mg daily) (6%) than in those receiving simvastatin monotherapy (2%); in addition, increases in aminotransferase or CK concentrations also occurred more frequently in patients receiving combination therapy (3 or 2%, respectively) than in those receiving simvastatin monotherapy (2 or 0%, respectively). There were no detectable adverse effects on growth or sexual maturation in adolescent boys or girls or on duration of menstrual cycle in girls. Use of ezetimibe in combination with simvastatin dosages exceeding 40 mg daily has not been evaluated in adolescents; safety and efficacy of ezetimibe, alone or in fixed combination with simvastatin, have not been evaluated in prepubertal girls or in children younger than 10 years of age.
Safety and efficacy of ezetimibe in fixed combination with bempedoic acid have not been established in pediatric patients.
Category C. (See Users Guide.)
Category X for fixed combination of ezetimibe and simvastatin (due to simvastatin component). (See Users Guide.)
Ezetimibe is distributed into milk in rats. It is not known whether ezetimibe is distributed into milk in humans. Because many drugs are distributed into human milk, caution should be used if ezetimibe is used in nursing women; the drug should not be used in nursing women unless the potential benefits justify the possible risks to the infant.
In clinical studies in patients receiving ezetimibe, 28% of patients were 65 years of age or older, and 5% of patients were 75 years of age or older. Following administration of ezetimibe (10 mg daily for 10 days), plasma concentrations of the drug were approximately twofold higher in geriatric individuals (65 years of age or older) than in younger adults; however, no overall differences in safety and efficacy of ezetimibe have been observed in geriatric patients relative to younger adults. Nevertheless, the manufacturer states that the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.
In clinical studies in patients receiving ezetimibe in fixed combination with simvastatin, 32% of patients were 65 years of age or older, and 8% of patients were 75 years of age or older. No substantial differences in safety or efficacy of the fixed-combination preparation were observed in geriatric patients relative to younger patients; however, greater sensitivity in some older patients cannot be ruled out. Because advanced age (65 years of age or older) is a risk factor for myopathy, including rhabdomyolysis, ezetimibe in fixed combination with simvastatin should be used with caution in geriatric patients.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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