Composition, form of production and packaging
Tablets covered with a film membrane of white or almost white color, oval, biconcave; on a cross section - almost white.
fenofibrate 145 mg
Auxiliary substances: corn starch - 137 mg, silicon colloidal dioxide - 10 mg, croscarmellose sodium - 33 mg, mannitol - 170 mg, magnesium stearate - 6 mg, povidone K-30 - 44 mg, cellulose microcrystalline - 105 mg.
Composition of the film shell: Opadrai II white - 20 mg, incl. polyvinyl alcohol - 9.38 mg, macrogol (polyethylene glycol 4000) - 4.72 mg, talc - 3.48 mg, titanium dioxide - 2.42 mg.
7 pcs. - packings cellular planimetric (4) - packs cardboard.
7 pcs. - packings cellular planimetric (12) - packs cardboard.
7 pcs. - packings cellular planimetric (14) - packs cardboard.
10 pieces. - packings of cellular contour (1) - packs cardboard.
10 pieces. - packings cellular planimetric (2) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (5) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
10 pieces. - packings cellular planimetric (9) - packs cardboard.
10 pieces. - packings cellular planimetric (10) - packs cardboard.
14 pcs. - packings cellular planimetric (2) - packs cardboard.
14 pcs. - packings cellular planimetric (6) - packs cardboard.
14 pcs. - packings cellular planimetric (7) - packs cardboard.
15 pcs. - packings cellular planimetric (2) - packs cardboard.
15 pcs. - packings cellular planimetric (4) - packs cardboard.
15 pcs. - packings cellular planimetric (6) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Lipid-lowering drug. Activating RAPP-alpha (? -receptors activated by the peroxisome proliferator), fenofibrate enhances lipolysis and removal from the blood plasma of atherogenic lipoproteins with a high triglyceride content by activating the lipoprotein lipase and reducing the synthesis of CIII apoproteins. Activation of PPA-alpha also results in increased synthesis of apo-proteins AI and AII.
Fenofibrate is a derivative of fibroic acid, whose ability to change the lipid content in the human body, is mediated by the activation of PAPP-alpha. The effects of fenofibrate on lipoproteins described above lead to a decrease in the content of the fraction of LDL and VLDL, including apoprotein B (apo B), and an increase in the content of the HDL fraction, including apoprotein AI (apo AI) and apo-protein AII (apo AII).
In addition, due to the correction of the disorders in the synthesis and catabolism of VLDL, fenofibrate increases the clearance of LDL and reduces the content of dense and small particle size of LDL, the increase of which is observed in patients with atherogenic lipid phenotype, a frequent violation in patients with IHD risk.
In clinical trials, it was noted that the use of fenofibrate reduces the concentration of total cholesterol by 20-25% and triglycerides by 40-55% with an increase in the concentration of HDL-cholesterol by 10-30%. In patients with hypercholesterolemia, whose LDL cholesterol concentration is reduced by 20-35%, the use of fenofibrate led to a decrease in the ratios: total cholesterol / HDL-cholesterol, LDL-cholesterol / HDL-cholesterol and apo B / apo AI, markers of atherogenic risk.
Given the significant effect of fenofibrate on the concentration of LDL cholesterol and triglycerides, the use of fenofibrate is effective in patients with hypercholesterolemia, either accompanied or not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, for example, in type 2 diabetes mellitus.
During treatment with fenofibrate, extravascular deposits of cholesterol (tendon and tuberous xanthomas) can be significantly reduced and even completely lost.
In patients with increased fibrinogen concentration, who received fenofibrate treatment, there was a significant decrease in this index, as well as in patients with elevated lipoprotein content. When treating fenofibrate, there is a decrease in the concentration of C-reactive protein and other markers of inflammation.
For patients with dyslipidemia and hyperuricemia, an additional advantage is the uricosuric effect of fenofibrate, which leads to a decrease in the uric acid concentration by approximately 25%.
In a clinical trial and in experimental animal studies , fenofibrate has been shown to reduce platelet aggregation caused by adenosine diphosphate, arachidonic acid, and epinephrine.
Fenofibrate Canon 145 mg, film-coated tablets, contain 145 mg of micronized fenofibrate, which has a higher bioavailability. C max in blood plasma is achieved 4-5 hours after ingestion. With prolonged use, the concentration of the drug in the blood plasma remains stable. Absorption of fenofibrate is enhanced by simultaneous intake with food.
Phenofibroic acid binds strongly to blood plasma albumin (more than 99%). The drug does not cumulate after a single dose and with prolonged use.
The initial fenofibrate in plasma is not detected. In the blood plasma, only the main metabolite, fenofibroic acid, is found. Fenofibrate is not a substrate for the CYP3A4 isoenzyme. Does not participate in microsomal metabolism.
It is mainly excreted by the kidneys in the form of fenofibric acid and glucuronide conjugate. T 1/2 of fenofibroic acid - about 20 hours. Within 6 days fenofibrate is excreted almost completely. Fenofibrate is not excreted in hemodialysis.
Pharmacokinetics in specific patient groups
The total clearance of fenofibric acid, determined in elderly patients, does not change.
Apply in combination with diet:
- simultaneously with inhibitors of HMG-CoA reductase (statins) as part of combined therapy for mixed dyslipidemia (type lla, llb by Fredrickson), in order to reduce triglycerides and increase HDL-C concentration in patients with ischemic heart disease or at high risk of developing coronary heart disease (other clinical forms of atherosclerotic diseases: atherosclerosis of peripheral arteries, abdominal aortic aneurysm and symptomatic carotid atherosclerosis, diabetes mellitus, multiple risk factors that correspond to a 10-year risk of coronary events> 20% );
- to reduce the concentration of triglycerides in patients with severe hyperglyceridemia (dyslipidemia IV, V type by Fredrickson);
- in order to reduce the elevated concentrations of LDL, total cholesterol, triglycerides and apoB and increase the HDL concentration in patients with primary hyperlipidemia or mixed dyslipidemia (type Ila, llb, III, IV according to Fredrickson).
The drug is taken orally, with food. Tablets should be swallowed whole, without chewing.
The drug should be taken for a long time, while continuing to follow the diet, which the patient adhered to before the treatment with the drug Fenofibrate Canon.
Adults appoint 1 tablet. 1 time / day.
Patients taking 1 caps. fenofibrate 200 mg, can switch to taking Fenofibrate Kanon 145 mg without additional dose adjustment.
The maximum daily dose is 145 mg.
For elderly patients it is recommended to take 1 table. (145 mg) 1 time / day.
The use of the drug in patients with liver disease has not been studied.
Side effects when using the drug in therapeutic doses are given with frequency distribution and system-organ classes according to WHO classification: very often -? 1/10 of prescriptions (> 10%); often - from? 1/100 to <1/10 of appointments (> 1% and <10%); infrequently - from? 1/1000 to <1/100 of prescriptions (> 0.1% and <1%); rarely - from? 1/10 000 to <1/1000 appointments (> 0.01% and <0.1%); very rarely - <1/10 000 prescriptions (<0.01%).
On the part of the digestive system: often - abdominal pain, nausea, vomiting, diarrhea and flatulence of moderate severity, moderate increase in serum transaminase activity; infrequently - cases of pancreatitis, the formation of gallstones; very rarely - hepatitis. If you have symptoms of hepatitis (jaundice, itching), you should conduct laboratory tests and, in case of confirmation of hepatitis, cancel fenofibrate.
From the musculoskeletal system: rarely - diffuse myalgia, myositis, muscle spasm and weakness; very rarely - rhabdomyolysis, increased activity of CK.
From the cardiovascular system: infrequently - venous thromboembolism (pulmonary embolism, deep vein thrombosis).
From the hemopoietic system: rarely - increased hemoglobin and leukocytes.
From the nervous system: rarely - a headache.
From the respiratory system: very rarely - interstitial pneumopathy.
On the part of the reproductive system: rarely - sexual dysfunction.
From the skin and subcutaneous tissues: infrequent - rash, itching, hives, or photosensitivity reactions; rarely - alopecia; very rarely - photosensitization accompanied by erythema, the formation of blisters or nodules in areas of skin exposed to sunlight or artificial UV radiation (eg, a quartz lamp) in certain cases (even after months of use without any complications).
On the part of laboratory indicators: infrequently - an increase in the concentration of creatinine and urea in the blood serum.
- hepatic insufficiency (including biliary cirrhosis and persistent liver dysfunction of unclear etiology);
- renal failure of severe degree (CC <20 ml / min);
- chronic or acute pancreatitis, except for cases of acute pancreatitis due to severe hypertriglyceridemia;
- history of the gall bladder;
- the presence in the anamnesis of photosensitization or phototoxicity in the treatment of fibrates or ketoprofen;
- the period of lactation (breastfeeding);
- age under 18 years (effectiveness and safety not established);
- hypersensitivity to fenofibrate or other components of the drug.
With caution should apply the drug for hypothyroidism; in patients who abuse alcohol; patients with impaired renal function (QC more than 20 ml / min); elderly patients; with a history of hereditary muscle diseases; with the simultaneous use of oral anticoagulants, inhibitors of HMG-CoA reductase.
PREGNANCY AND LACTATION
There are few data on the use of fenofibrate in pregnant women. In experimental studies on animals, the teratogenic effect of fenofibrate was not observed.Embryotoxicity was noted during the use of the drug during preclinical trials at doses toxic to the mother organism. The potential risk for a person is unknown, therefore, during pregnancy, the preparation Fenofibrate Canon can be used only after a thorough assessment of the risk-benefit ratio.
The drug Fenofibrate Canon is contraindicated in breastfeeding (there is insufficient data on the use of the drug in this period).
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated use of the drug for renal failure of severe degree (CC <20 ml / min).
Caution should be given to patients with impaired renal function (CK> 20 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The use of the drug in patients with liver disease has not been studied.
Contraindicated use of the drug in liver failure (including biliary cirrhosis and persistent liver dysfunction of unclear etiology).
APPLICATION FOR CHILDREN
Contraindicated in the use of drugs under the age of 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
With caution should be used in elderly patients.
The recommended dose is 1 tablet. (145 mg) 1 time / day.
Before starting treatment with Fenofibrate Canon, appropriate treatment should be performed to eliminate the cause of secondary hypercholesterolemia, for example, in diseases such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, the consequences of drug therapy, alcoholism.
The effectiveness of therapy should be assessed by the content of lipids (total cholesterol, LDL, triglycerides) in serum. In the absence of a therapeutic effect after several months of therapy (usually after 3 months), the advisability of concomitant or alternative therapy should be considered.
In patients with hyperlipidemia, taking estrogens or hormonal contraceptives containing estrogens, it is necessary to find out whether hyperlipidemia has a primary or secondary nature. In such cases, an increase in the lipid content may be caused by the intake of estrogens.
With the use of fenofibrate and other drugs that reduce lipid concentrations, some patients described an increase in the activity of hepatic transaminases. In most cases, this increase was temporary, minor and asymptomatic. During the first 12 months of treatment, it is recommended to monitor the activity of transaminases (ALT, ACT) every 3 months. Patients who have increased transaminase concentrations against the background of treatment require attention, and in the case of increased ALT and ACT activity more than 3-fold compared with VGN, the drug should be withdrawn.
Cases of pancreatitis during the treatment with fenofibrate have been described. Possible causes of pancreatitis in these cases were: insufficient effectiveness of the drug in patients with severe hypertriglyceridemia, direct exposure to the drug, as well as secondary phenomena associated with the presence of stones or the formation of sediment in the gallbladder, accompanied by obstruction of the common bile duct.
When fenofibrate and other drugs that reduce lipid concentrations are used, cases of toxic effects on muscle tissue are described, including very rare cases of rhabdomyolysis. The frequency of this disorder increases in the case of hypoalbuminemia and renal failure in history. The possibility of this complication increases with hypoalbuminemia and renal insufficiency.
Toxic effects on muscle tissue may be suspected on the basis of patient complaints of weakness, diffuse myalgia, myositis, muscle spasms and convulsions and / or a marked increase in CK activity (more than 5 times compared with IGN). In these cases, treatment with fenofibrate should be discontinued.
The risk of rhabdomyolysis may increase in patients with a predisposition to myopathy and / or rhabdomyolysis, including age over 70 years, a history of hereditary muscle diseases, renal dysfunction, hypothyroidism, alcohol abuse. Such patients should be prescribed a drug only if the expected benefit exceeds the possible risk of rhabdomyolysis. When taking Fenofibrate Canon simultaneously with inhibitors of HMG-CoA reductase or other fibrates, the risk of serious toxic effects on muscle fibers increases, especially if the patient suffered from muscle disease before starting treatment. In this regard, the joint administration of the preparation Fenofibrate Canon and statin is allowed only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle disease and in close monitoring, aimed at revealing signs of the development of toxic effects on muscle tissue .
With the use of the preparation Fenofibrate Canon as a monotherapy or in combination with statins, a reversible increase in the serum creatinine concentration was noted in patients. The increase in creatinine concentration was generally stable for a time without signs of a further increase in serum creatinine concentration with prolonged therapy, with a tendency to return to baseline values вЂ‹вЂ‹after treatment withdrawal. The clinical significance of these observations is not established. In patients with renal failure, Fenofibrate Canon is recommended to monitor kidney function. Control of kidney function is also necessary in patients at risk of developing renal failure, namely, in elderly patients and patients with diabetes mellitus. Treatment should be discontinued in case of an increase in creatinine concentration> 50% of IGN. It is recommended to determine the concentration of creatinine during the first 3 months after the start of treatment, and also periodically after its termination.
Impact on the ability to drive vehicles and manage mechanisms
When applying the drug, there was no effect on the ability to drive and other mechanisms.
Cases of overdose are not described.
Treatment: if you suspect an overdose, you should prescribe a symptomatic and, if necessary, supportive treatment. The specific antidote is unknown. Hemodialysis is ineffective.
Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is due to the displacement of the anticoagulant from the binding sites to plasma proteins. At the beginning of treatment with fenofibrate, it is recommended that the dose of anticoagulants be reduced by about a third, followed by a gradual selection of a dose. Selection of a dose is recommended to be carried out under the control of INR.
Several severe cases of reversible renal dysfunction have been described with simultaneous treatment with fenofibrate and cyclosporine. Therefore, it is necessary to monitor the state of kidney function in such patients and to abolish fenofibrate in case of serious changes in laboratory parameters.
When fenofibrate is used simultaneously with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases.
Studies of human liver microsomes in vitro have shown that fenofibrate and fenofibric acid are not inhibitors of the following cytochrome P450 isoenzymes (CYP3A4, CYP2D6, CYP2E1 or CYP1A2). In therapeutic concentrations, these compounds are weak inhibitors of CYP2C19 and CYP2A6 isoenzymes and weak or moderate inhibitors of CYP2C9.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 2 years.