Fibrates

Fibrates

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Gemfibrozil and fenofibrate reduce plasma triglyceride by enhancing its clearance from plasma and reducing its hepatic production by stimulating the peroxisome proliferator-activated receptor (PPAR)-alpha family of nuclear receptors. There is a moderate increase in high-density lipoprotein (HDL) levels, and the effect on low-density lipoprotein (LDL) is variable.

Gemfibrozil has a short plasma half-life, but prolonged action, and may take some weeks to approach its full effect on lipid levels. Gemfibrozil is best absorbed if taken half an hour before food, but it can be taken with meals if gastrointestinal effects are troublesome. It should not be given in combination with repaglinide. Gemfibrozil increases the cholesterol content of bile and may predispose to gallstones. Gemfibrozil, both independently and when given in combination with a statin, increases the risk of myopathy, rhabdomyolysis and renal failure. Creatine kinase should be measured 1 month after starting combination therapy and at 6-month intervals or if symptoms occur.

Fenofibrate formulations changed in 2006 from capsules to tablets and even though the strengths are different, the current fenofibrate 48 mg tablet is equivalent to the previous 67 mg capsule, and the current 145 mg tablet is equivalent to the previous 160 mg one. The new formulations can be taken without regard to food. Fenofibrate can cause phototoxic reactions, and the patient should be advised to wear protective clothing and use sunscreen to avoid sun exposure to skin. Fenofibrate also increases the cholesterol content of bile, and may predispose to gallstones.