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Fenofibrate for Treatment of Hypertriglyceridemia
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Am Fam Physician. 1998 Nov 1;58(7):1656-1657.
Clofibrate and gemfibrozil are fibrates that increase lipoprotein lipase activity and triglyceride clearance, thus shifting the subgroup pattern of low-density lipoprotein (LDL) cholesterol to one that is less atherogenic. These effects appear to directly modify expression of several genes involved in lipoprotein metabolism; they also decrease hepatic secretion of very-low-density lipoprotein (VLDL) cholesterol and release of fatty acids from adipose tissue. This reduction of VLDL leads to decreased transfer of cholesterol from high-density lipoprotein (HDL) to VLDL, thus increasing serum HDL levels. Medical Letter consultants reviewed micronized fenofibrate, which was recently labeled for this purpose by the U.S. Food and Drug Administration, to determine if it offers any advantage over currently available fibrates.
The micronized form of fenofibrate is more rapidly and completely absorbed than the standard formulation, which is available outside the United States. A 67-mg micronized capsule of fenofibrate is the bioequivalent of a 100-mg, non-micronized tablet. Taking the drug with food increases the rate of absorption, and plasma concentration reaches a peak in six to eight hours. Fenofibrate has a half-life of approximately 20 hours and is metabolized in the liver and excreted mainly in the urine.
Few studies have been published regarding the micronized form of fenofibrate. Comparative studies in patients with hypercholesterolemia and hypertriglyceridemia have demonstrated that micronized fenofibrate, in a dosage of 200 mg daily, decreased LDL cholesterol levels slightly less than did a dosage of 20 mg of simvastatin or pravastatin daily, but it had a significantly greater effect on triglyceride levels. The decrease in triglyceride levels was about 30 to 50 percent, with slightly greater increases (1 to 34 percent) in HDL cholesterol levels. In one randomized study, atorvastatin (in a dosage of 10 or 20 mg daily) was less effective than non-micronized fenofibrate (in a dosage of 100 mg three times daily) in lowering triglyceride levels or in raising HDL cholesterol levels. Atorvastatin was, however, more effective in lowering LDL cholesterol levels. Although few study comparisons of gemfibrozil and fenofibrate have been conducted, fenofibrate appears to have more favorable effects on the lowering of LDL cholesterol levels.
No data are available on the effects of fenofibrate on morbidity and mortality from coronary heart disease. Although randomized trials with other fibrates have shown slower progression to coronary atherosclerosis and a decrease in the incidence of coronary events, there was no effect on the total mortality rate. Although clofibrate reduced the number of coronary events, the total mortality rate was increased because of an increase in malignant and gastrointestinal disease.
The most commonly reported adverse effects of micronized fenofibrate are rash and gastrointestinal symptoms. Increases in serum creatinine concentrations have been reported and, as with other fibrates, cholelithiasis, hepatitis and myositis can also occur. All fibrates, including micronized fenofibrate, potentiate the effects of oral anticoagulant medications. It is unclear if fenofibrate increases the risk of rhabdomyolysis when taken concurrently with a statin drug. If micronized fenofibrate is used with cholestyramine or colestipol, it should be taken one hour before or four to six hours after the resin. Fenofibrate may also increase the nephrotoxicity of cyclosporin.
Micronized fenofibrate is available in 67-mg capsules. The manufacturer recommends an initial dosage of 67 mg, taken once daily with a meal, increasing at four- to eight-week intervals (if necessary) to a maximum dosage of 201 mg daily. The drug should not be used in patients with hepatic or severe renal impairment. The authors conclude that once-daily doses of micronized fenofibrate lower elevated serum triglyceride concentrations, raise serum HDL cholesterol levels and improve LDL cholesterol levels. Based on currently available data, fenofibrate appears to be more convenient than gemfibrozil and may have more favorable effects on LDL cholesterol levels.
Medical Letter consultants. Fenofibrate for hypertriglyceridemia. Med Letter Drugs Ther. July 3, 1998;40(1030):68–9.
Copyright © 1998 by the American Academy of Family Physicians.
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