Pharmacological action Fenofibrate 160 mg
Hypolipidemic agent from a group of derivatives fibroevoy acid. Fenofibrate has the ability to modify the contents of lipids in the human organism due to activation of receptors RAPP-alpha (α-receptors, peroxisome proliferator-activated). RAPP-alpha activation also leads to increased synthesis of apoproteins AI and AII.
Fenofibrate is a derivative fibroevoy acid, which is the ability to modify the contents of lipids in the human body is mediated by activation of the RAPP-alpha.
The above-described action of fenofibrate on lipoproteins lead to a decrease in the content fraction of LDL and VLDL, which include the apoprotein B (apo B), and increased levels of HDL fraction, which include the apoprotein A-I (apo A-I) and apoprotein A-II (apo A -II).
In addition, due to the correction of violations of synthesis and catabolism of VLDL, fenofibrate increases LDL clearance and reduces the content of small and dense LDL particles (increase of LDL cholesterol observed in patients with atherogenic lipid phenotype is accompanied by a high risk of CHD).
In clinical studies, it was noted that the use of fenofibrate lowers total cholesterol by 20-25% and triglycerides by 40-55% with an increase in the level of HDL-C by 10-30%. In patients with hypercholesterolemia, in which the level of LDL-C decreased by 20-35% the use of fenofibrate resulted in a decline in the ratio: total XC / HDL-C, Hs-LPNP/Hs-LPVP and apo B / apo A-I, are markers of atherogenic risk.
Given the significant effect of fenofibrate on the level of LDL-C and triglycerides, the use of the drug is effective in patients with hypercholesterolemia whether unaccompanied or accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, such as diabetes mellitus type 2.
During treatment with fenofibrate can significantly decrease or even disappear entirely extravascular deposition c (tendon and tuberous xanthomas). In patients with elevated levels of fibrinogen, treated with fenofibrate, a significant reduction in this indicator, as well as in patients with elevated lipoprotein. Fenofibrate in the treatment of a decrease in the concentration of C-reactive protein and other markers of inflammation.
For patients with dyslipidemia, and hyperuricemia additional advantage is that fenofibrate exerts urikozurichesky effect, which leads to a decrease in uric acid concentration by approximately 25%.
In the clinical study and animal experiments have shown that fenofibrate reduces the platelet aggregation induced by adenosine diphosphate, arachidonic acid and epinephrine.
Pharmacokinetics Fenofibrate 160 mg
Suction
After oral administration, fenofibrate 145 mg Cmax achieved within 2-4 hours, Cmax in blood plasma and the total effect of micronised fenofibrate in the form of nanoparticles (fenofibrate 145 mg) does not depend on the simultaneous reception of food (and the drug can be taken at any time, regardless of the meal ).
Fenofibrate 160 mg in the form of film-coated tabletkok has a higher bioavailability compared with the earlier dosage forms of fenofibrate. After ingestion of the dosage form of fenofibrate Cmax plasma levels reached after 4-5 hours after ingestion. With prolonged use of plasma concentrations remained stable.
Distribution
Fenofibric acid steady and more than 99% bound to plasma albumin. The drug does not accumulates after a single dose and after prolonged use.
Metabolism
After oral administration, fenofibrate rapidly hydrolyzed by esterases. The plasma is found only major active metabolite of fenofibrate – fenofibric acid. With prolonged use the concentration of fenofibric acid in plasma is stable, regardless of the individual patient. Fenofibrate is not a substrate for CYP3A4, is not involved in the microsomal metabolism.
Breeding
T1 / 2 – 20 h. Write, mainly in the urine as fenofibric acid and glucuronide conjugates. Within 6 days, fenofibrate appears almost completely.
Pharmacokinetics in special clinical situations
Elderly patients total clearance fenofibric acid does not change.
When hemodialysis is not displayed.
Statement Fenofibrate 160 mg
- Hypercholesterolemia and hypertriglyceridemia isolated or mixed (dyslipidemia, type IIa, IIb, III *, IV, V *) with the ineffectiveness of non-drug therapies (including hypolipidemic diet, weight loss, increased physical activity), especially when associated with dyslipidemia risk factors such as hypertension and smoking;
- Secondary hyperlipoproteinemia, when hyperlipoproteinemia persists despite effective treatment of underlying disease (eg, dyslipidemia, diabetes).
* In clinical studies, the drug fenofibrate in tablets of 160 mg participated only a few patients with dyslipidemia III and V-type.
Dosing regimen Fenofibrate 160 mg
Adults appoint 1 tablet (145 mg or 160 mg), 1 time per day.
Patients taking 1 capsule of fenofibrate 200 mg can go to receive 1 tablet of fenofibrate 145 mg or 160 mg dose without additional correction. Patients taking 1 tablet of fenofibrate 160 mg, can go to receive 1 tablet of fenofibrate 145 mg no additional dose adjustment.
Elderly patients are encouraged to nominate a standard dose for adults.
Use of the drug in patients with liver disease is not known.
Fenofibrate 145 mg taken at any time of day, regardless of the meal, the pill should be swallowed whole without chewing, with a glass of water.
The drug should take a long time, while continuing to follow a diet, which the patient adhered to prior to treatment with fenofibrate.
Side effect Fenofibrate 160 mg
From the digestive system: (> 1 / 100, 1 / 1000, 1 / 10 000, 1 / 1000,1 / 10 000,
CNS and peripheral nervous systems: (1 / 10 000,
With the respiratory system: (
From the laboratory parameters: (1 / 1000,
Allergic reactions: (1 / 1000,
Dermatological reactions: (1 / 10 000.1 / 1000) – Alopecia; (
Contraindications Fenofibrate 160 mg
- Hepatic impairment (including cirrhosis);
- Severe renal insufficiency (creatinine clearance
- Gallbladder disease;
- Congenital galactosemia, lactase deficiency, malabsorption of glucose and galactose (product contains lactose);
- Congenital fruktozemiya, lack of sucrose-izomaltazy (product contains sucrose);
- A history of allergic reaction to peanuts, peanut butter, soy lecithin or related products (in conjunction with the risk of hypersensitivity reactions);
- Childhood and adolescence to 18 years;
- Lactation (breastfeeding);
- A history of photosensitivity or phototoxicity in the treatment of fibrates or ketoprofen;
- Hypersensitivity to the drug.
With care given to patients with hepatic and / or renal failure, hypothyroidism, patients who abuse alcohol, elderly patients, when specifying a history of hereditary muscle diseases, while taking oral anticoagulants, inhibitors of HMG-CoA reductase.
Application of pregnancy and breastfeeding Fenofibrate 160 mg
Data on the use of fenofibrate in pregnancy are scarce. The potential risk for humans is unknown. Use of the drug during pregnancy is only possible if the intended benefits to the mother outweighs the potential risk to the fetus.
Due to the lack of safety data, use during lactation (breastfeeding) is contraindicated.
In experimental animal studies, teratogenic effects of fenofibrate has not been detected. Embryotoxicity noted in the introduction to the doses toxic to the maternal organism.
Use in hepatic dysfunction
Contraindicated in hepatic impairment (including cirrhosis);
Use in renal impairment
Contraindicated in severe renal insufficiency (creatinine clearance
Cautions
Before you start therapy with fenofibrate, there should be an appropriate treatment to eliminate the causes of secondary hypercholesterolemia, for example, in diseases such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, the effects of drug therapy, alcoholism.
Effectiveness of therapy should be evaluated on the content of lipids (total cholesterol, LDL, triglycerides) in blood serum. In the absence of therapeutic effect after several months of therapy (usually after 3 months) should consider the advisability of concomitant or alternative therapy.
Patients with hyperlipidemia receiving estrogen or hormonal contraceptives containing estrogen, you should determine whether hyperlipidemia primary or secondary nature. In such cases, improvement in lipid levels may be caused by estrogen.
When receiving fenofibrate and other drugs that lower lipid concentrations, some patients have described increased activity of hepatic transaminases. In most cases, this increase was temporary, minor and asymptomatic. During the first 12 months of treatment is recommended to control the level of liver enzymes (ALT, ACT) every 3 months. Patients who during treatment with increased concentrations of transaminases, requiring attention, in the case of increasing the concentration of ALT and the ACT more than 3 times compared with CAH receiving the drug is discontinued.
Have been described cases of pancreatitis during treatment with fenofibrate. Possible causes of pancreatitis in these cases were: lack of efficacy in patients with severe hypertriglyceridemia, a direct effect of the drug, as well as secondary effects associated with the presence of stones or the formation of sludge in the gall bladder, accompanied by obstruction of the common bile duct.
When receiving fenofibrate and other drugs that lower lipid concentrations, described cases of toxic effects on muscle tissue, including the very rare cases of rhabdomyolysis. The frequency of such a violation increases if hypoalbuminemia and renal failure in history. The possible occurrence of this complication increases in cases of hypoalbuminemia and renal failure.
Toxic effect on muscle tissue can be suspected based on the patient’s complaints of weakness, diffuse myalgia, myositis, muscle spasms and cramps, and / or a pronounced increase in the activity of CK (more than 5 times as compared to CAH). In these cases, treatment with fenofibrate should be discontinued.
The risk of rhabdomyolysis may be increased in patients with a predisposition to myopathy and / or rhabdomyolysis, including age older than 70 years, weighed down by history of hereditary muscle disease, renal failure, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit exceeds the potential risk of rhabdomyolysis.
When concomitantly with inhibitors of HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers especially if the patient prior to treatment suffered muscle diseases. In this regard, the joint appointment of fenofibrate and a statin is permissible only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle diseases and in conditions of close monitoring aimed at identifying the signs of toxic effects on muscle tissue.
In case of increase of serum creatinine by more than 50% above the ULN, treatment should be suspended. In the first 3 months of treatment is recommended to determine the concentration of creatinine.
Effects on ability to drive vehicles and management mechanisms
Before the drug was not observed effect on ability to drive and control mechanisms.
Overdose Fenofibrate 160 mg
Cases of overdosage have not been described.
Treatment: symptomatic conduct and, if necessary, supportive therapy. The specific antidote is known. Hemodialysis is ineffective.
Drug Interactions Fenofibrate 160 mg
Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of anticoagulant from the binding sites to plasma proteins. At the beginning of treatment with fenofibrate is recommended to reduce the dose of anticoagulants by about a third, followed by gradual titration. Titration is recommended to control the level of MHO.
Described several cases of severe reversible decrease of renal function during simultaneous treatment with fenofibrate and cyclosporine. It is therefore necessary to monitor the status of renal function in these patients and cancel fenofibrate in case of serious changes in laboratory parameters.
When receiving fenofibrate together with inhibitors of HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers.
Studies of human liver microsomes in vitro demonstrated that fenofibrate and fenofibric acid are not inhibitors of isozymes CYP3A4, CYP2D6, CYP2E1 or CYP1A2. At therapeutic concentrations, these compounds are weak inhibitors of CYP2C19 and CYP2A6 isozymes, and weak or moderate inhibitors of CYP2C9.
