Generality
Fibrate drugs are drugs used to decrease triglyceride and cholesterol levels in the blood.
The use of similar medicines, therefore, is indicated in all those patients in whom the blood levels of the aforementioned fats are so high as to constitute a pathological condition capable of compromising their health and putting their lives at risk.
Fibrate drugs can be administered either as monotherapy or in combination therapy with other drugs indicated for the treatment of dyslipidemia, such as statins . However, it should be pointed out that fibrates are not first choice drugs for the treatment of hypercholesterolemia and hypertriglyceridemia.
What are
What are Fibrated Drugs?
Fibrate drugs are a class of drugs capable of reducing plasma cholesterol and triglyceride concentrations. To be fair, it should be pointed out that fibrates are able to more effectively decrease the high levels of triglycerides compared to those of cholesterol, for this reason, they tend to be used when hypertriglyceridemia is also associated with hypercholesterolemia.
From the chemical point of view, fibrates are analogues of phenoxyisobutyric acid ; in this regard, it is recalled that, for the therapeutic action, the presence of the isobutyric group is of fundamental importance. The fibrates currently available on the market are, in fact, prodrugs that become active - carrying out their activity - only after having met their metabolism.
Active Principles belonging to the Fibrate Class
The active ingredients belonging to the class of fibrates used in the therapeutic field in Italy are:
- Fenofibrate ;
- Gemfibrozil ;
- The bezafibrate .
Fenofibrate is available in medicinal products both as the sole active ingredient and in association with statins.
Did you know that ...
Although the fibrate-statin association is included in the treatment of various dyslipidemia, it raises some doubts about the safety of use. More in detail, the main concerns deriving from the combined use of these two classes of drugs concern the potential increase in the risk of onset of myopathies. This increased risk appears to be greater when the gemfibrozil fibrate drug is associated with statins. Not surprisingly, the medicinal products currently available in Italy containing a fibrate and a statin in combination are based on fenofibrate.
Brief History of Fibrated Drugs
The hypolipidemizing action of the fibrate drugs was discovered in 1962 by two researchers from Imeprial Chemical Industries, but it was only in 1967 that the forefather of the class of fibrates - in detail, the clofibrate - obtained the marketing authorization on the US market by the FDA (Food and Drug Administration). However, based on the data collected during the years in which this active ingredient entered therapy, it emerged that, although it was able to reduce blood cholesterol levels, it was not as capable of reducing the fatal cardiovascular events deriving from the conditions of hypercholesterolemia and hypertriglyceridemia. In addition to this, it was observed that the use of the same active ingredient in the therapeutic field was closely related to cases of gallstones. Therefore, clofibrate fell into disuse in favor of other fibrate drugs considered more effective and safe, such as for example fenofibrate (available in some European states as early as 1975) and gemfibrozil (introduced in therapy in 1981).
Therapeutic indications
When to use Fibrated Medicines
Fibro drugs are not considered first choice drugs in the treatment of dyslipidemias, in fact, they are used only when non-pharmacological strategies against dyslipidemia (diet, reduction in body weight, physical activity, etc.) are not effective, or when they are not it is possible to administer the first choice drugs.
More in detail, the use of this class of drugs is indicated:
- In the treatment of dyslipidemias characterized by increased levels of triglycerides that do not respond to dietary treatment;
- In the treatment of mixed dyslipidemias characterized by both hypercholesterolemia and hypertriglyceridemia when the latter is of greater clinical relevance and when the dietary treatment does not produce the desired effects;
- In the treatment of severe hypertriglyceridemia associated or not with low HDL values;
- In the treatment of primary hypercholesterolemia when the use of statins is contraindicated or not tolerated.
In addition to the above, the use of fibrates is also indicated in male patients to prevent the risk of cardiovascular diseases in the presence of high blood cholesterol levels and when the use of statins is not possible.
Please note
Since the therapeutic indications may vary depending on the active ingredient that is required to be used, for detailed and exhaustive information, see the reading of the illustrative leaflet of the medicinal product prescribed by the doctor.
Action mechanism
How do Fibrate Drugs work?
As mentioned, fibrate drugs are able to reduce blood triglyceride levels more markedly than it does due to high cholesterol levels; however, the exact mechanism of action by which these drugs perform their activity has not yet been fully clarified. Despite this, it has been shown that fibrates:
- They significantly reduce VLDL (Very Low Density Lipoproteins,
lipoproteins with high triglyceride content);
- They induce a moderate increase in HDL (High Density Lipoproteins, also known as "good cholesterol", it is a lipoprotein with a very low triglyceride content but high in cholesterol);
- They produce variable effects on LDL (Low Density Lipoproteins, lipoproteins with a low triglyceride content but containing greater amounts of cholesterol).
From the studies carried out so far it has emerged that the reduction of VLDL levels is mainly due to two mechanisms of action exerted by fibrate drugs, such as: stimulation of lipoprotein lipase activity (enzyme responsible for triglyceride removal from VLDL) and stimulation fatty acid oxidation mediated by receptors activated by alpha-type peroxisomal proliferators (PPARα).
The effects of increasing HDL, on the other hand, appear to be exerted through an increase in apolipoprotein A-1 synthesis .
In addition to this, all fibrates are able to accelerate the turnover and removal of cholesterol from the liver .
For more information on the effectiveness of fibrate drugs, see also: Fibrates and Cholesterol.
Side effects
What side-effects do fibrotic drugs cause?
Although the side effects may vary slightly depending on the active ingredient prescribed to the patient, some of them are common to the whole class of fibrates. More in detail, following treatment with fibrates it is possible to develop side effects such as:
- Headache;
- Gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, diarrhea and flatulence;
- Pancreatitis;
- Anemia, thrombocytopenia, leukopenia, eosinophilia, pancytopenia;
- Cholelithiasis, cholestasis, cholestatic jaundice, altered liver function and hepatitis;
- Muscular weakness, myalgia, arthralgia, rhabdomyolysis;
- Impotence and changes in libido.
Furthermore, the possibility of the onset of allergic reactions in sensitive individuals should not be forgotten.
However, despite what has been said so far, fibrates are generally well tolerated by most patients.
Pregnancy and breastfeeding
Can Fibrated Medicines Be Used in Pregnancy and During Lactation?
Although the studies performed on animals have not reported cases of teratogenicity deriving from the administration of fibrates during gestation, there are no adequate studies conducted on the safety of use of the product in pregnant women. For this reason, the use of fibrate drugs is generally contraindicated in pregnant women.
Likewise, it is not known whether fibrates are excreted in breast milk; therefore, as a precautionary measure, their use is contraindicated even during breastfeeding.
Contraindications
When Do Not Use Fibrated Medicines
As with the side effects, the contraindications to the use of fibrate drugs may also vary slightly depending on the active ingredient to be used. However, it is possible to state that the use of fibrate drugs - both in monotherapy and in combination therapy - is contraindicated in the following cases:
- Known hypersensitivity to the active ingredient and / or to any of the excipients contained within the medicinal product to be used;
- In patients with liver disease, except for hepatic steatosis because it is a condition frequently associated with hypertriglyceridemia;
- In patients suffering from renal insufficiency and who are undergoing renal dialysis;
- In patients with gallbladder disease characterized by cholelithiasis or not;
- In patients who have experienced photoallergic or phototoxic reactions following the administration of fibrates;
- In pregnancy and during lactation.
Finally, it is worth remembering that the use of fibrate drugs in association with statins is generally contraindicated in patients with predisposing factors to myopathy (for example, impaired renal function, severe infections, diabetes, hypothyroidism, advanced age, etc.) .
