fibrate

Fibrate, or fibric acid derivative, is a class of lipid-lowering medications used primarily to reduce triglycerides and raise high-density lipoprotein (HDL) cholesterol. The most commonly prescribed fibrates include fenofibrate and gemfibrozil. Other older members include bezafibrate and clofibrate. Fibrates are indicated for severe hypertriglyceridemia and for certain mixed dyslipidemias; they may reduce pancreatitis risk in patients with very high triglycerides.

Fibrates act as agonists of the peroxisome proliferator-activated receptor alpha (PPAR-α). Activation increases oxidation of fatty acids, upregulates lipoprotein lipase, decreases hepatic production of very-low-density lipoprotein (VLDL), and alters apolipoprotein expression. The net effect is lower triglycerides and modest HDL elevation; LDL can rise, fall, or stay the same depending on baseline pattern.

Used as monotherapy or in combination with statins in selected patients with mixed dyslipidemia or high triglycerides. They may be particularly useful in patients with metabolic syndrome or diabetes who have persistent hypertriglyceridemia despite dietary measures.

Fenofibrate dosing is commonly around 145 mg once daily; gemfibrozil is commonly 600 mg twice daily with meals. Fibrate efficacy is reduced in renal impairment, and dosing requires adjustment. They are metabolized in the liver and excreted in urine and bile.

Common adverse effects include gastrointestinal symptoms, dyspepsia, and elevated liver enzymes. Gallstone formation has been reported. Myopathy and rhabdomyolysis risk increases with concomitant statin therapy, particularly with gemfibrozil; fenofibrate has a lower risk when used with statins. Contraindications include significant liver or kidney disease and active gallbladder disease. Use in pregnancy is typically avoided.