2.21 Fibrates

The two fibrates are fenofibrate and gemfibrozil.  The action of fibrates are not totally understood. The fibrates act by four main mechanisms:

• Reduce the availability of substrate for triglyceride synthesis in the liver;
• promotion of the action of lipoprotein lipase which degrades circulating lipoproteins in the blood therefore reducing the circulating levels of circulating triglycerides
• modulation of low-density lipoprotein (LDL) receptor/ligand interaction and
• stimulation of reverse cholesterol transport which is the main pathway for the return of excess cholesterol from peripheral tissues to the liver for excretion in bile.

The overall effect is to reduce circulating cholesterol but this class of cholesterol lowering medicines is not as effective as the statins.

Use

Fibrates, used primarily to manage lipid disorders, require careful consideration in specific patient populations. They are contraindicated in individuals with severe renal or hepatic impairment and during pregnancy. Additionally, caution is advised when fibrates are used in conjunction with statins due to the increased risk of myopathy and related complications.

Side effects and precautions

Generally well tolerated, fibrates can cause some changes in liver function tests (LFTs), though there is little evidence to suggest progression to severe liver conditions such as liver failure or hepatitis.

Common adverse effects, occurring in more than 1% of patients, include gastrointestinal disturbances and a reversible increase in serum creatinine levels.

Less frequently, affecting 0.1-1% of patients, fibrates may lead to gallstones, pancreatitis, and photosensitivity.

Rarely, occurring in fewer than 0.1% of cases, adverse effects can include cholestatic jaundice, anemia, leucopenia, myopathy, rhabdomyolysis, and allergic reactions such as angioedema.

In practice, it is recommended to monitor aminotransferase levels every three months during the first year of fenofibrate therapy, discontinuing the drug if levels exceed three times the upper limit of normal (ULN).