Drug Profile

Fenofibrate was first marketed in France in 1975.[1] The drug was approved in the U.S. in 1993, but the manufacturer chose not to market it until clearance was granted by the Food and Drug Administration (FDA) in February 1998 for a micronized (the drug ground into a smaller particle size) version. There is no known therapeutic advantage of the micronized product over the older, nonmicronized one, but the new patent on this dosage form allowed the manufacturer, Abbott Laboratories, to extend its period of patent exclusivity.

Fenofibrate is approved by the FDA for treatment of specific types of high cholesterol and triglycerides (another type of blood fat). Studies in people using two drugs in the same family as fenofibrate (clofibrate and gemfibrozil) showed that drugs in this class increase the risk of cancer, pancreatitis (inflammation of the pancreas), gallstones and problems from gallstone surgery. Most importantly, they caused an overall increase in mortality. Long-term human studies have not been done with fenofibrate, but studies in rats found an increased risk of liver, pancreatic and testicular tumors.

Following approval of fenofibrate, use of the drug was linked to rare cases of severe drug-induced liver injury, which in some cases has resulted in liver transplantation and death.[2] Drug-induced liver injury has been reported within the first few weeks of treatment with the drug or after several months of therapy. Importantly, in clinical trials of fenofibrate, subjects who received the drug were more likely to develop blood-test abnormalities indicative of liver injury than subjects who received a placebo.[2]

Fenofibrate appears to share risks of psychiatric adverse events with other cholesterol-lowering drugs. Aggressive behavior; memory impairment; mood changes; and cognitive, sleep and perception disorders, such as nightmares, have been reported with the use of many drugs used to treat high cholesterol: fenofibrate, gemfibrozil (LOPID), ezetimibe (ZETIA), clofibrate and the statin drugs, such as fluvastatin (LESCOL), rosuvastatin (CRESTOR) and simvastatin (ZOCOR).[3],[4] Though researchers have not yet established a direct link between these reports and the use of the cholesterol-lowering drugs listed, patients should be alert to this possibility and report unexpected changes to their doctor.

The drug also may cause myopathy (muscle damage), including rhabdomyolysis, which can lead to acute kidney failure and death. This risk is highest when fenofibrate is taken concomitantly with colchicine (COLCRYS, MITIGARE) or with a statin, particularly in elderly patients and patients with diabetes, kidney failure or hypothyroidism (low thyroid hormone levels). Fenofibrate also is associated with severe life-threatening allergic reactions, known as anaphylaxis and angioedema.

Severe decreases in HDL ("good") cholesterol levels occurring in diabetic and nondiabetic patients initiated on fibrate therapy were reported in post-marketing and clinical trials. This decrease has been reported to occur from two weeks to multiple years after initiation of fibrate therapy.[5]

Cases of severe sudden allergic reactions, including anaphylaxis and angioedema, have been linked to use of fenofibrate. [2]

Regulatory actions surrounding fenofibrate

2011: The FDA announced that fenofibric acid (TRILIPIX) might not lower the risk of having a heart attack or stroke.[6] Fenofibric acid is the active breakdown product (metabolite) of fenofibrate. Fenofibrate and fenofibric acid can therefore be considered the same drug.

The FDA now requires the product labels for fenofibrate and fenofibric acid to contain the following statement in the “Important Limitations of Use” section:

Fenofibrate at a dose equivalent to 135 milligrams of TRILIPIX did not reduce coronary heart disease morbidity and mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus.[7]