Fenofibrate, one of the most popular fibrates
|Use||hypertriglyceridemia and hypercholesterolaemia|
In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents.
Fibrates prescribed commonly are:
- Bezafibrate (e.g. Bezalip)
- Ciprofibrate (e.g. Modalim)
- Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones)
- Gemfibrozil (e.g. Lopid)
- Fenofibrate (e.g. TriCor)
- Clinofibrate (e.g. Lipoclin)
Fibrates are used in accessory therapy in many forms of hypercholesterolemia, usually in combination with statins. Clinical trials do support their use as monotherapy agents. Fibrates reduce the number of non-fatal heart attacks, but do not improve all-cause mortality and are therefore indicated only in those not tolerant to statins.
Although less effective in lowering LDL levels, the ability of fibrates to increase HDL and lower triglyceride levels seems to reduce insulin resistance when the dyslipidemia is associated with other features of the metabolic syndrome (hypertension and diabetes mellitus type 2). They are therefore used in many hyperlipidemias. Due to a rare paradoxical decrease in HDL-C seen in some patients on fenofibrate, as per US FDA label change, it is recommended that the HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline. Medwatch
In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis, idiosyncratic destruction of muscle tissue, leading to renal failure. A powerful statin drug, cerivastatin (Lipobay), was withdrawn because of this complication. The less lipophilic statins are less prone to cause this reaction, and are probably safer when combined with fibrates.
Although used clinically since the 1930s, if not earlier, the mechanism of action of fibrates remained unelucidated until, in the 1990s, it was discovered that fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation.
Fibrates are a substrate of (metabolized by) CYP3A4.
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