Fenofibrate

Fenofibrate is a fibric acid derivative used to treat abnormal lipid levels, particularly high triglycerides. It lowers plasma triglyceride concentrations and can modestly raise high-density lipoprotein (HDL) cholesterol. It is used as monotherapy or as an adjunct to diet in adults with hyperlipidemia and certain types of dyslipidemia, and may be considered for severe hypertriglyceridemia to reduce pancreatitis risk.

Mechanism of action is primarily through activation of peroxisome proliferator-activated receptor alpha (PPAR-alpha). This leads to increased lipoprotein lipase activity, reduced hepatic production of triglyceride-rich very low-density lipoprotein (VLDL), and enhanced clearance of triglyceride-rich particles. The net effect is lower triglycerides and, to a lesser extent, changes in HDL and LDL cholesterol.

Fenofibrate is usually taken orally as capsules or tablets. It is a prodrug that is hydrolyzed to the active metabolite, fenofibric acid. It is absorbed with meals and is eliminated mainly in the urine.

Contraindications include active liver disease or significant hepatic impairment, severe renal impairment, gallbladder disease, and pregnancy or lactation when alternatives are available. Caution is advised in patients with liver or kidney disease and in the elderly. Coadministration with statins can increase the risk of myopathy or rhabdomyolysis; caution and monitoring are advised. Fenofibrate can also interact with anticoagulants, potentially altering bleeding risk, and with bile acid sequestrants, which may affect absorption of the drug.

Common adverse effects include abdominal discomfort, nausea, dyspepsia, headache, and elevated liver enzymes. Gallstone formation has been reported with fibrates in susceptible individuals.