Fibrates Ezetimibe

A recently developed antihyperlipidemic is ezetimibe (Zetia, A.113) (Figure A.31). Ezetimibe inhibits the absorption of cholesterol across the intestinal wall. Like fibrates, ezetimibe is often prescribed with statins, although the effectiveness of ezetimibe has recently been called into question. A compound that may soon be approved for the treatment of high cholesterol is anacetrapib (A.114). Anacetrapib, a product of Merck, is currently in phase III trials. The compound inhibits cholesteryl ester transfer protein (CETP). The net effect of CETP inhibition is elevated HDL cholesterol and lower LDL cholesterol levels. 

FIBRATES EZETIMIBE Risk of gallstones with fibrates Uncertain Stop co-administration if symptoms develop... 

Keywords dyslipidaemia, LDL-cholesterol, small dense LDL, HDL-cholesterol, statins, fibrates, ezetimibe, nicotinic acid. 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

The absorption of highly lipophilic drugs (atorvastatin, simvastatin, ezetimibe, fibrates) may be reduced in cholestasis if they require bile salts for their absorption. 

A statin could be considered in this patient with appropriate monitoring. Fibrates, niacin or ezetimibe could be used with appropriate monitoring of LFTs. Colestyramine/colestipol and acipimox should be safe to use. 

Pravastatin is the statin of choice in this patient as it is least likely to accumulate, is hydrophilic, and is not highly protein bound. The starting dose should be low and should be increased cautiously. Monitoring of LFTs is required. Colestyramine and colestipol may be considered and may help the patient s pruritus. Niacin and acipimox could be used if the pruritus does not worsen. The fibrates should be avoided because of the risk of gallstone formation. Ezetimibe could be considered alone. 

Statins should be avoided. If absolutely necessary, pravastatin could be used, starting at a low dose and with cautious adjustment according to clinical response. The patient s synthetic liver function should be monitored closely. In the event of the slightest deterioration of function, pravastatin should be stopped immediately. Colestyramine/colestipol should be safe to use but may cause a reduction in vitamin K absorption and increase the risk of a bleed. Constipation might induce encephalopathy. The fibrates should be avoided due to their potential effect on coagulopathy. Ezetimibe should be safe to use alone. Acipimox and niacin are gastric irritants and would be best avoided. 

Currently available treatments against atherosclerosis include cholesterol-lowering drugs such as statins, fibrates, nicotinic acid (NA) [8-13] and the cholesterol intestinal absorption inhibitor, ezetimibe (Fig. 1) [14]. 

Treatment a statin or a combination of a statin and ezetimibe for raised isolated hypercholesterolaemia or combined dyslipidaemia fibrates and/or high doses of omega-3 fatty acids (2 g x 2 daily) in isolated fasting hypertriglyceridemia (>3.4 mmol/L or... 

Despite these seemingly favourable results, the UK manufacturers of ezetimibe state that the safety of eombined use with fibrates is not yet established. This is because both fibrates and ezetimibe increase cholesterol excretion into the bile, which could promote the production of gallstones. They say that if gallstones or gall bladder disease is suspected then the combination should be discontinued. 

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