Fenofibrat

Fenofibrat is a fibric acid derivative used to treat dyslipidemias. It is a prodrug that is hydrolyzed to fenofibric acid, the active component. It activates peroxisome proliferator-activated receptor alpha (PPAR-α), increasing fatty acid oxidation and lipoprotein lipase activity, decreasing hepatic triglyceride synthesis and VLDL production, leading to lower triglycerides and a modest rise in HDL; LDL reduction is variable.

Indications include reduction of triglycerides in adults with hypertriglyceridemia, treatment of mixed dyslipidemia, and lowering the risk of pancreatitis from very high triglycerides. It is used as an adjunct to diet when response to diet and exercise is inadequate. Fenofibrate is not generally proven to reduce cardiovascular risk as monotherapy and is often used when statins are insufficient or contraindicated.

Pharmacokinetics and dosing: fenofibrate is taken by mouth, with meals to improve absorption. Doses range from 48 mg to 145 mg daily depending on the formulation and indication. The drug is metabolized to fenofibric acid and eliminated primarily by the kidneys, requiring dose adjustment in renal impairment. The half-life supports once-daily dosing.

Safety and monitoring: common adverse effects include gastrointestinal symptoms, headache, dizziness, and rash. Hepatic transaminase elevations and gallstone formation can occur. Myopathy risk increases with concurrent statin therapy; rare cases of rhabdomyolysis have been reported. Contraindications include severe liver or kidney disease, biliary obstruction or gallbladder disease, pregnancy and breastfeeding in certain circumstances. Patients should be monitored with liver enzymes and lipid panels, and CK measurement if myopathy symptoms occur.