Fenofibrate is, among other fibrates, a variation of clofibric acid. Thereby, it belongs to the lipid-lowering agents like nicotinic acids as well as statins. An increased level of triglycerides is the main spectrum of action of fenofibrate. A cholesterol-lowering effect is less characteristic here, but still present.
What is fenofibrate?
Fenofibrate (chemical name: 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropionic acid isopropyl ester) belongs to the drug group of fibrates, which form an important drug therapy for the treatment of hyperlipidemia, that is, elevated blood lipids. In this context, fenofibrate is mainly used to treat an increased concentration of triglycerides in the blood by lowering them. This contrasts with statins, which are primarily used to treat elevated cholesterol levels. Nevertheless, fenofibrate can also be used to treat cholesterol in the blood. However, its main effect is still on triglycerides, which is why it is also primarily used for elevated triglycerides in the blood. Disturbed lipid metabolism should be treated as soon as possible to ensure protection from secondary diseases, such as diseases of the cardiovascular system. The first choice is statins, which guarantee a strong lipid lowering. Fenofibrate and other fibrates are only second choice and are mainly used when statins are not tolerated during therapy or when primarily only triglycerides, not cholesterol, are elevated. Fenofibrate is a white, insoluble, crystalline powder that is given compactly as a tablet or capsule. After fenofibrate is ingested, it is broken down to clofibric acid, which is then excreted in the urine, which is why the dose should be adjusted if there is renal impairment.
Pharmacologic effects on the body and organs
The main effect of fenofibrate is to lower plasma levels of triglycerides. On the other hand, exactly how this happens has not been researched. However, it can be assumed that it has several effects. One is that fenofibrate activates PPARα. This is the peroxisome proliferator activated receptor, which after binding fenofibrate itself binds to the DNA and there influences the reading of some genes and thus also changes the fat metabolism. On the one hand, it causes a greater degradation of the “bad” cholesterol LDL (approx. 10 – 25 %). In addition, there is a moderate increase in HDL (approx. 10 %). The “bad” cholesterol is called so because it is deposited in the vessels and thus causes atherosclerosis. In contrast, the “good” cholesterol transports the fats out of the vessels, for example, and causes their degradation. In addition, fenofibrate causes a reduced release of VLDL from the liver, which is also involved in calcifying processes of the vessel wall. Fenofibrate also activates lipoprotein lipase, which promotes the breakdown of blood lipids. Other effects of fenofibrate are mainly related to the vascular wall, where the inflammatory process is stopped by also reducing the formation of inflammatory proteins. Another effect of fenofibrate is that it promotes the risk of developing cholesterol-containing gallstones.
Medical use and use for treatment and prevention.
The main indication of fenofibrate is elevated blood triglyceride levels. This may result from a primary disorder of lipid metabolism, that is, a congenital form of hypertriglyceridemia (increased concentration of triglycerides in the blood), or a secondary disorder, that is, an acquired form of hypertriglyceridemia. The latter can have various causes, for example a faulty diet, which can lead to obesity, but also anorexia. Some metabolic disorders such as diabetes increase blood lipids. But kidney disease is also to blame for elevated levels of triglycerides. Secondary hypertriglyceridemia can also be iatrogenically caused, that is, by the physician prescribing lipid-increasing drugs, such as beta-blockers or cortisone. Another possible application of fenofibrate is metabolic syndrome. This is a dangerous combination of disturbed carbohydrate metabolism, obesity, increased blood pressure, as well as disturbed fat metabolism (triglycerides are increased, while HDL is decreased).Fenofibrate is taken in the form of capsules or tablets. The half-life is around 22 hours, which makes it the longest acting fibrate. The dose is 200 mg once a day.
Risks and side effects
Fenofibrate can cause both nonspecific side effects and specific side effects that are typical of fibrates. Nonspecific ones include allergic reactions to the drug, which are associated with typical swelling, breathing problems, as well as hives. Other more non-specific side effects include chills with fever and flu-like feeling, headache, swelling of the lower extremities, impotence, as well as joint pain. In addition, dizziness and lightheadedness may occur. Since fenofibrate affects the gastrointestinal tract, non-specific symptoms may also occur, such as nausea, vomiting, diarrhea. Likewise, unwanted weight gain may occur. Specific to fenofibrate is muscle breakdown (rhabdomyolysis). Patients experience severe muscle pain, cramps, and general weakness. Other lipid-lowering agents such as statins can also induce rhabdomyolysis. Therefore, combination therapy with fenofibrate should be avoided. Another typical side effect of fenofibrate is that it increases the likelihood of developing cholesterol stones of the bile. Fenofibrate is contraindicated in gallbladder disease, liver disease, renal insufficiency, and in nursing mothers and pregnant women.
