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Ezetimibe
drug data and news
Ezetimibe drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Ezetimibe | ||
| Brand Names/Synonyms | Ezedoc; Ezetimibe; Ezetimibe [Usan:Inn]; Ezetimibe [Usan]; Vytorin; Zetia | ||
| Indication | For use as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors. | ||
| Mechanism Of Action | Ezetimibe localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. | ||
| Ezetimibe News (When available) |
Anti-cholesterol drug combo okay for muscles Feb 22, 2006 Research and Markets: Pfizer's Atorvastatin + Torcetrapib ... Feb 17, 2006 Merck profits edge ahead in fourth quarter Feb 1, 2006 Pharmac Agrees To Fund Vytorin Cholestrol Drug Feb 1, 2006 Schering-Plough Reports Financial Results for 2005 Fourth Quarter ... Jan 30, 2006 Pharmac Agrees To Fund Vytorin Cholestrol Drug Feb 1, 2006 Merck profits edge ahead in fourth quarter Feb 1, 2006 Ask the Doctor: Causes of muscle weakness vary Jan 23, 2006 The Need for Preventing Cardiovascular Disease Jan 11, 2006 Merck/Schering-Plough Announces Update for the IMPROVE-IT Trial Nov 15, 2005 Ask the Doctor: Statin can affect muscles Dec 5, 2005 The Doctor's Choice Awards Dec 9, 2005 New Data Examines Effects of CRESTOR(R) Alone or in Combination ... Nov 15, 2005 New Data Examines Effects of CRESTOR(R) Alone or in Combination ... Nov 15, 2005 Govt medicine spending slammed as 'pathetic' Dec 5, 2005 Control a key to cholesterol Nov 11, 2005 Dr. Gaff's Column Nov 28, 2005 Crestor combo cuts bad cholesterol 65 percent Nov 15, 2005 New study confirms lower cholestrol better Nov 16, 2005 Zocor as good as Lipitor Nov 15, 2005 Statin intolerance: what now? Nov 8, 2005 Physicians Predict that Combination Therapy will Play an ... Nov 22, 2005 Schering-Plough Reports 2005 Third Quarter Financial Results Oct 24, 2005 Very Low LDL Levels Appear to Be Safe in Coronary Artery Disease Oct 17, 2005 Latest Statistics Show 30 Percent of Seniors Using Statins in 2002 Oct 11, 2005 Latest Statistics Show 30 Percent of Seniors Using Statins in 2002 11 Oct 2005 Genes affect response to cholesterol drug Sep 21, 2005 Beximco Pharma launches 'Ezeta' for heart patients Sep 25, 2005 Merck signs unique drug development deal Sep 16, 2005 Ezetimibe, muscle link highlighted Aug 9, 2005 Beximco Pharma launches two new drugs Aug 28, 2005 Heart failure drug advised for PBS Aug 30, 2005 Research and Markets: The Next 10 Years will see Six Statins Lose ... Aug 17, 2005 TREATMENT OF HYPERCHOLESTEROLEMIA IN PREGNANCY: RISKS VERSUS ... Aug 31, 2005 Launch Code Aug 10, 2005 Schering-Plough and Sankyo Enter License Agreement for Olmesartan ... Aug 4, 2005 New Analysis in Patients with Type 2 Diabetes from Trial with ... Jul 23, 2005 Kos Reports 49% Increase in Revenue to $179.4 Million, Earnings ... Aug 4, 2005 Cholesterol-combo drug Jul 29, 2005 Schering-Plough Reports Financial Results for 2005 Second Quarter Jul 21, 2005 PHARMAC welcomes increased budget for 2006 year Jul 25, 2005 AstraZeneca licenses cholesterol drug class from Avanir Jul 12, 2005 Harding inventor honored for drug Jul 8, 2005 | ||
| Dosage Forms | TABLET | ||
| Drug_Category | Anticholesteremic Agents; Cholesterol Absorption Inhibitors; ATC:C10AX09 | ||
| Absorption | Not Available | ||
| Interactions |
-->Interactions for Ezetimibe: Cholestyramine: Concomitant cholestyramine administration decreased the mean AUC of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding ezetimibe to cholestyramine may be reduced by this interaction. Fibrates: The safety and effectiveness of ezetimibe administered with fibrates have not been established. Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis. In a preclinical study in dogs, ezetimibe increased cholesterol in the gallbladder bile. Co-administration of ZETIA with fibrates is not recommended until use in patients is studied. Fenofibrate: In a pharmacokinetic study, concomitant fenofibrate administration increased total ezetimibe concentrations approximately 1.5-fold. Gemfibrozil: In a pharmacokinetic study, concomitant gemfibrozil administration increased total ezetimibe concentrations approximately 1.7-fold. HMG-CoA reductase inhibitors: No clinically significant pharmacokinetic interactions were seen when ezetimibe was co-administered with atorvastatin, simvastatin, pravastatin, lovastatin, or fluvastatin. Cyclosporine: The total ezetimibe level increased 12-fold in one renal transplant patient receiving multiple medications, including cyclosporine. Patients who take both ezetimibe and cyclosporine should be carefully monitored. Carcinogenesis, Mutagenesis, Impairment of Fertility A 104-week dietary carcinogenicity study with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). A 104-week dietary carcinogenicity study with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). There were no statistically significant increases in tumor incidences in drug-treated rats or mice. No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation. In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test. In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Pregnancy Pregnancy Category: C There are no adequate and well-controlled studies of ezetimibe in pregnant women. Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus. In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats and rabbits during organogenesis, there was no evidence of embryolethal effects at the doses tested (250, 500, 1000 mg/kg/day). In rats, increased incidences of common fetal skeletal findings (extra pair of thoracic ribs, unossified cervical vertebral centra, shortened ribs) were observed at 1000 mg/kg/day (~10 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). In rabbits treated with ezetimibe, an increased incidence of extra thoracic ribs was observed at 1000 mg/kg/day (150 times the human exposure at 10 mg daily based on AUC0-24hr for total ezetimibe). Ezetimibe crossed the placenta when pregnant rats and rabbits were given multiple oral doses. Multiple dose studies of ezetimibe given in combination with HMG-CoA reductase inhibitors (statins) in rats and rabbits during organogenesis result in higher ezetimibe and statin exposures. Reproductive findings occur at lower doses in combination therapy compared to monotherapy. All HMG-CoA reductase inhibitors are contraindicated in pregnant and nursing women. When ZETIA is administered with an HMG-CoA reductase inhibitor in a woman of childbearing potential, refer to the pregnancy category and package labeling for the HMG-CoA reductase inhibitor. Labor and Delivery The effects of ZETIA on labor and delivery in pregnant women are unknown. Nursing Mothers In rat studies, exposure to total ezetimibe in nursing pups was up to half of that observed in maternal plasma. It is not known whether ezetimibe is excreted into human breast milk; therefore, ZETIA should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant. Pediatric Use The pharmacokinetics of ZETIA in adolescents (10 to 18 years) have been shown to be similar to that in adults. Treatment experience with ZETIA in the pediatric population is limited to 4 patients (9 to 17 years) in the sitosterolemia study and 5 patients (11 to 17 years) in the HoFH study. Treatment with ZETIA in children (<10 years) is not recommended. Geriatric Use Of the patients who received ZETIA in clinical studies, 948 were 65 and older (this included 206 who were 75 and older). The effectiveness and safety of ZETIA were similar between these patients and younger subjects. Greater sensitivity of some older individuals cannot be ruled out. | ||
| Toxicity | Not Available | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxy-propyl]-4-(4-hydroxyphenyl)-azetidin-2-one | ||
| Chemical Formula | C24H21F2NO3 | ||
| Molecular Weight | 409.425 g/mol | ||
| Smiles String | C1=CC(=CC=C1C2C(C(=O)N2C3=CC=C(C=C3)F)CCC(C4=CC=C(C=C4)F)O)O | ||
| Melting Point | Not Available | ||
| Water Solubility | Not Available | ||
| State | Solid | ||
| LogP/Hphobicity | 4.584 | ||
| Isoelectric Point | Not Available | ||
| Biotransformation | Not Available | ||
| Half Life | 22 hours | ||
| Protein Binding [%] | >90% | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.drugs.com/cons/Ezetimibe.html http://www.rxlist.com/cgi/generic/ezetimibe.htm | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00619 | ||
| CAS Registry Number | 163222-33-1 | ||
| KEGG Compound ID | C13464 | ||
| PubChem ID | SID:727861 | ||
| PharmGKB ID | Not Available | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | 2247521 |
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