fibratos

Fibratos, or fibrates, are a class of lipid-modifying drugs that activate peroxisome proliferator-activated receptor alpha (PPAR-α). Activation increases lipoprotein lipase activity and fatty acid oxidation in the liver, resulting in reduced hepatic production of very-low-density lipoprotein (VLDL) and enhanced clearance of triglyceride-rich particles. The clinical effect is a marked decrease in plasma triglycerides, a modest rise in high-density lipoprotein (HDL) cholesterol, and variable effects on low-density lipoprotein (LDL).

Common agents include gemfibrozil, fenofibrate, and bezafibrate. Fenofibrate is a prodrug that is hydrolyzed to fenofibric acid, the active form; gemfibrozil is active itself. Pharmacokinetics vary by compound, with renal impairment requiring dose adjustments in some cases.

Indications: primary or secondary hypertriglyceridemia with risk of pancreatitis and mixed dyslipidemia. They are generally not first-line for lowering LDL cholesterol and may be used when triglycerides predominate or when statins are not tolerated, though combination therapy with statins requires caution because of myopathy and rhabdomyolysis risk.

Adverse effects include GI upset, cholelithiasis, liver enzyme elevations, and myopathy, particularly when used with statins. Rhabdomyolysis is rare but more likely in patients with renal impairment or at high doses.

Contraindications: active liver disease, gallbladder disease, biliary tract disorders, and severe renal impairment. Caution is advised during pregnancy and lactation depending on local guidelines.

Interactions: enhanced anticoagulant effects with warfarin and increased myopathy risk with concomitant statin therapy, especially with gemfibrozil.