Ezetimibe about

Ezetimibe interferes with the absorption of cholesterol from the brush border of the intestine, a novel mechanism that makes it a good choice for adjunctive therapy. It is approved as both monotherapy and for use with a statin. The dose is 10 mg once daily, given with or without food. When used alone, it results in an approximate 18% reduction in LDL cholesterol. When added to a statin, ezetimibe lowers LDL by about an additional 12% to 20%. A combination product (Vytorin) containing ezetimibe 10 mg and simvastatin 10, 20, 40, or 80 mg is available. Ezetimibe is well tolerated approximately 4% of patients experience GI upset. Because cardiovascular outcomes with ezetimibe have not been evaluated, it should be reserved for patients unable to tolerate statin therapy or those who do not achieve satisfactory lipid lowering with a statin alone. 

Elderly Plasma concentrations for total ezetimibe were about 2-fold higher in older (65 years of age and older) healthy subjects compared with younger subjects. Pregnancy Category C. 

The effect of ezetimibe on cholesterol absorption is constant over the dosage range of 5-20 mg/d. Therefore, a single daily dose of 10 mg is used. Average reduction in LDL cholesterol with ezetimibe alone in patients with primary hypercholesterolemia is about 18%, with minimal increases in HDL cholesterol. It is also effective in patients with phytosterolemia. Ezetimibe is synergistic with reductase inhibitors, producing decrements as great as 25% in LDL cholesterol beyond that achieved with the reductase inhibitor alone. 

In a patent reported for ezetimibe Form-S, it was disclosed that ezetimibe hydrated Form-FI was converted to ezetimibe anhydrated Form-A when heated at about 40 °C. The ezetimibe Form-S itself was produced by isolating the hydrated Form-FI or anhydrous Form-A from ferf-butanol [11]. 

Recent data indicate that ezetimibe inhibits a specific transport process in jejunal enterocytes, which take up cholesterol from the lumen. The putative transport protein is Niemann-Pick Cl-hke 1 protein (NPCILI). In wild-type mice, ezetimibe inhibits cholesterol absorption by about 70% in NPCILI knockout mice, cholesterol absorption is 86% lower than in wild-type mice, and ezetimibe has no effect on cholesterol absorption. Ezetimibe does not affect intestinal triglyceride absorption. In human subjects, ezetimibe reduced cholesterol absorption by 54%, precipitating a compensatory increase in cholesterol synthesis, which can be inhibited with a cholesterol synthesis inhibitor such as a statin. There is also a substantial reduction of plasma levels of plant sterols (campesterol and sitosterol concentrations are reduced by 48 and 41%, respectively), indicating that ezetimibe also inhibits intestinal absorption of plant sterols. 

In a study of 40 healthy hypercholesterolaemic subjects, colesly-ramine 4 g twice daily decreased the mean AUC of ezetimibe by about 80% and decreased the mean AUC of total ezetimibe (ezetimibe plus metaboUtes) by about 55%. Colestyramine may therefore be expected to decrease the lipid-loweiing effects of ezetimibe. Note that ezetimibe undei oes enterohepatic recirculation, so separating administration may not fully resolve this interaction. 

Information about the interaction between ezetimibe and rifampicin appears to be limited to these studies, which were primarily designed to investigate ezetimibe disposition. However, it seems likely that the effects of ezetimibe will be reduced in patients who are also given multiple doses... 

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