Ezetimibe adverse effects

Once absorbed, ezetimibe undergoes extensive glucuronida-tion in the intestinal wall to the active metabolite (ezetimibe glucuronide). Ezetimibe and the active metabolite are entero-hepatically recirculated back to the site of action, which limits systemic exposure and may explain the low incidence of adverse effects (Table 9-9). Ezetimibe alone or with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in LFTs. Currently, clinical trials designed to determine ezetimibe s effects on CHD morbidity and mortality have not been completed. The time until maximum effect on lipids for ezetemibe is generally 2 weeks. 

Ezetimibe is a selective potent inhibitor of the intestinal absorption of dietary and biliary cholesterol. A total of 432 patients were included in a pooled analysis of two phase-II studies, both lasting for 12 weeks ezetimibe was well tolerated, with an adverse events profile similar to that of placebo (1). In 668 patients who took ezetimibe with simvastatin, the adverse effects were similar to those with simvastatin alone (2). 

In 668 patients ezetimibe was given with simvastatin and adverse effects were similar to those experienced with simvastatin alone (8). 

Ezetimibe is used for secondary prevention against established atherosclerotic CVD to achieve an optimal atherogenic cholesterol level in patients with intolerance to high-doses of statins. It can further be used in combination with statins to achieve lower LDL-C levels in very-high-risk patients [59]. Ezetimibe inhibits the Niemann-Pick Cl-Like 1 (NPClLl)-dependent intestinal cholesterol absorption in the apical brush border membrane of jejuna enterocytes [14], and thus it only moderately lowers LDL-C (12-25 %) [60]. Meanwhile, common adverse effects associated with ezetimibe therapy include gastrointestinal disturbances, while infrequent adverse effects such as rash, angioedema, anaphylaxis, hepatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis may occur [46]. 

Ezetimibe Inhibits cholesterol absorption across the intestinal border fCholesterol 4LDL Lew adverse effects effects additive to other drugs... 

Ezetimibe rarely can cause allergic reactions. It has been associated with myopathy, more commonly in association with statins but also when used as monotherapy. The mechanism for this adverse effects is unknown. The safety of ezetimibe during pregnancy has not been established. Since all statins are contraindicated in pregnant and nursing women, combination products containing ezetimibe and a statin should not be used by women in childbearing years in the absence of contraception. 

Ezetimibe generaiiy is weii toierated. The most common adverse effects are listed above. Whenever ezetimibe is used in combination with an HMGRi, the incidence of myopathy or rhabdomyolysis does not increase above that seen with HMGRI monotherapy (15,21). 

Skeletal muscle effects In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the relevant control arm (placebo or HMG-CoA reductase inhibitor alone). However, myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs. 

Some combinations of lipid-altering drugs are currently available such as extended-release niacin/lovastatin and ezetimibe/simvastatin, which are more promising for lipid-lowering therapy with stronger effects and decreased adverse reactions. 

In a three-arm study, patients were given simvastatin 80 mg daily, simvastatin 80 mg daily with ezetimibe 10 mg daily, or simvastatin 40 mg daily with ezetimibe 10 mg daily. No difference in adverse events was noted between each of the 3 groups and there were no significant elevations in creatine kinase. No cases of myopathy or rhabdomyolysis occurred, and the combination was well-tolerated. In another study, ezetimibe 0.25 mg, 1 mg or 10 mg daily had no effect on the pharmacokinetics of simvastatin 10 mg daily, when both were given for 14 days. In addition, 10 and 20-mg doses of simvastatin were well-tolerated in combination with ezetimibe. ... 

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