Fenofybrat | Fenofibrate Canon tablets coated. 145 mg 30 pcs.

Pharmacological action

Pharmaceutical group:

Hypolipidemic drug.

Pharmacological action:

By activating RAPP-alpha (alpha receptors activated by the peroxisome proliferator), fenofibrate enhances lipolysis and excretion of atherogenic lipoproteins with a high content of triglycerides from the blood plasma by activating lipoprotein lipase and reducing the synthesis of apIII protein CIII. Activation of RAPP-alpha also leads to increased synthesis of apoproteins AI and II.

Fenofibrate is a derivative of fibroic acid, the ability of which to change the lipid content in the human body is mediated by the activation of RAPP-alpha. The effects of fenofibrate on lipoproteins described above lead to a decrease in the content of the low lipoprotein fraction (LDL) and very low density (VLDL), which include apoprotein B, and an increase in the content of the high density lipoprotein fraction (HDL), which include apoproteins AI and AII .

In addition, due to the correction of violations of the synthesis and catabolism of VLDL, fenofibrate increases the clearance of LDL and reduces the content of dense and small particle size of LDL, an increase which is observed in patients with an atherogenic lipid phenotype, a frequent violation in patients at risk of coronary heart disease. During clinical studies, 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, in which the concentration of LDL-cholesterol 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 "A by B / A by AI ", which are markers of atherogenic risk.

Given the significant effect on the concentration of LDL cholesterol and triglycerides, the use of fenofibrate is effective in patients with hypercholesterolemia, both with and without hypertriglyceridemia, including secondary hyperlipoproteinemia, for example, with type 2 diabetes mellitus. During treatment with fenofibrate, extravascular cholesterol deposits (tendon and tuberous xanthomas) can significantly decrease and even completely disappear. In patients with elevated fibrinogen levels treated with fenofibrate, a significant decrease in this indicator was noted, as well as in patients with elevated lipoproteins. Other markers of inflammation, such as C-reactive protein, also decrease with fenofibrate treatment.

For patients with dyslipidemia and hyperuricemia, an additional advantage is the uricosuric effect of fenofibrate, which leads to a decrease in uric acid concentration by approximately 25%.

Clinical studies and animal experiments have shown that fenofibrate reduces platelet aggregation caused by adenosine diphosphate, arachidonic acid, and epinephrine.

Pharmacokinetics:

Drug Fenofibrate Canon in the form of micronized fenofibrate has a higher bioavailability.

The initial plasma fenofibrate is not detected. The main plasma metabolite is fenofibroic acid.

Absorption:

Cmax 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 when taken with food.

Distribution:

fenofibroic acid binds strongly to plasma albumin (more than 99%).

Elimination half-life: T1 / 2 of fenofibroic acid - about 20 hours.

Metabolism and excretion:

in plasma is found only the main metabolite of fenofibrate - fenofibroic acid. Fenofibrate is not a substrate for the CYP3A4 isoenzyme. It does not participate in microsomal metabolism.

It is excreted mainly by the kidneys in the form of fenofibroic acid and glucuronide conogate. Within 6 days, fenofibrate is excreted almost completely. The total clearance of fenofibroic acid, determined in elderly patients, does not change.

The drug does not cumulate after a single dose and with prolonged use. With hemodialysis is not displayed.

Indications

- combination therapy with HMG-CoA reductase inhibitors (statins) of mixed dyslipidemia (type lla, llb according to Fredrickson), in order to reduce triglycerides (TG) and increase HDL concentration in patients with coronary artery disease or with a high risk of developing coronary artery disease (other clinical forms of atherosclerotic disease: peripheral arterial atherosclerosis, abdominal aortic aneurysm and symptomatic carotid atherosclerosis diabetes are multiple risk factors that correspond to 10- summer risk of developing coronary complications> 20%)

- to reduce the concentration of TG in patients with severe hyperglyceridemia (dyslipidemia IV, V type according to Fredrickson)

- to reduce p increased concentrations of LDL, total cholesterol, triglycerides and ApoB (apolipoprotein B) and increased concentrations of HDL in patients with primary hyperlipidemia or mixed dyslipidemia (type lla, llb, III, IV according to Fredrickson).

Contraindications

- hypersensitivity to fenofibrate or other components of the drug

- liver failure (including biliary cirrhosis and persistent impaired liver function of unclear etiology)

- severe renal failure (creatinine clearance < 20 ml / min)

- age under 18 years of age (efficacy and safety have not been established)

- history of photosensitization or phototoxicity in the treatment of fibrates or ketoprofen

- history of gall bladder history

- breastfeeding

chronic or except in cases of acute pancreatitis due to severe hypertriglyceridemia.

Precautions: in case of hypothyroidism in patients who abuse alcohol, with impaired renal function (CC more than 20 ml / min) of advanced age, with a burdened history of hereditary muscle diseases while taking oral anticoagulants, HMG-CoA reductase inhibitors (see section “Interaction with other drugs”).

Use during pregnancy and lactation

Pregnancy.

There is little evidence of the use of fenofibrate in pregnant women. In animal experiments, the teratogenic effect of fenofibrate was not observed. Embryotoxicity was observed when prescribing doses that were toxic to the mother's body during preclinical trials. The potential risk to humans is unknown. Therefore, during pregnancy, the drug Fenofibrat Canon can be used only after a thorough assessment of the ratio of risk and benefit.

Breastfeeding period.

The drug Fenofibrat Canon is contraindicated for use during breastfeeding (there is insufficient data on the use of the drug in this period).

Special instructions

Before starting treatment with Fenofibrat 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 effects of drug therapy, alcoholism.

The effectiveness of therapy should be evaluated by the content of lipids (total cholesterol, LDL, triglycerides) in the blood serum. In the absence of a therapeutic effect after several months of therapy (usually after 3 months), the appropriateness of concomitant or alternative therapy should be considered.

In patients with hyperlipidemia who are taking estrogens or hormonal contraceptives containing estrogens, it is necessary to determine whether hyperlipidemia is of primary or secondary nature. In such cases, an increase in lipid levels may be caused by estrogen intake.

Liver function: when taking fenofibrate and other drugs that lower lipid concentrations, some patients have described an increase in the activity of “liver” 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 (alanine aminotransferase (ALT), aspartate aminotransferase (ACT) every 3 months. Patients who have increased transaminase concentrations during treatment need attention, and if the concentration of ALT and ACT is more than 3 times higher than the upper limit of the norm, the drug is stopped.

Pancreatitis: Cases of pancreatitis during treatment with fenofibrate have been described. Possible causes of pancreatitis in these cases were: insufficient drug efficacy 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.

Muscles: when taking fenofibrate and other drugs that lower lipid concentrations, cases of toxic effects on muscle tissue have been described, including very rare cases of rhabdomyolysis. The frequency of such a disorder increases in the case of hypoalbuminemia and a history of renal failure. The possibility of this complication increases in cases of hypoalbuminemia and renal failure.

Toxic effects on muscle tissue may be suspected based on patient complaints of weakness, diffuse myalgia, myositis, muscle cramps and cramps and / or a marked increase in creatinine phosphokinase (CPK) activity (more than 5-fold compared with the upper limit of normal). In these cases, treatment with fenofibrate must be discontinued.

The risk of developing rhabdomyolysis may increase in patients with a predisposition to myopathy and / or rhabdomyolysis, including age over 70, a history of hereditary muscle diseases, impaired renal function, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit exceeds the possible risk of rhabdomyolysis. When taking Fenofibrate Canon along with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases, especially if the patient suffered from muscle disease before treatment. In this regard, the combined use of the drug Fenofibrate Canon and statia is permissible only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle disease and under close monitoring aimed at identifying signs of the development of toxic effects on muscle tissue .

Renal function: When using the drug Fenofibrat Canon as monotherapy or in combination with statins, a reversible increase in serum creatinine concentration was noted in patients. The increase in creatinine concentration, in general, was stable over time with no signs of a further increase in serum creatinine concentration during prolonged therapy, with a tendency to return to the initial values ​​after treatment was canceled. The clinical significance of observational data has not been established. In patients with renal insufficiency, the use of Fenofibrat Canon is recommended to monitor renal function. Monitoring of renal function is necessary for patients at risk of developing kidney failure, namely, elderly patients and patients with diabetes mellitus. Treatment should be canceled in case of an increase in creatinine concentration> 50% of the upper limit of normal. It is recommended to determine the concentration of creatinine during the first 3 months after the start of treatment, as well as periodically after its completion.

Effect on the ability to drive a car and other mechanisms: When using the drug, no effect on the ability to drive a car and other mechanisms was noted.

Composition

1 tab: - fenofibrate 145 mg

Excipients:

corn starch - 137 mg,

silicon dioxide colloid - 10 mg,

croscarmellose sodium - 33 mg,

magnesium - mannitol ,

povidone K-30 - 44 mg,

microcrystalline cellulose - 105 mg.

Composition of the film coat:

Opadray II white - 20 mg, including polyvinyl alcohol - 9.38 mg,

macrogol - 4.72 mg,

talcum powder - 3.48 mg,

titanium dioxide - 2.42 mg.

Dosage and administration of

Tablets should be swallowed whole without chewing, at the same time as eating.

Adults: One tablet once daily. Patients taking one 200 mg fenofibrate capsule can switch to taking one tablet of Fenofibrate Canon 145 mg without additional dose adjustment. The maximum daily dose of 145 mg.

Elderly patients: It is recommended to take 1 tablet of 145 mg for adults (one tablet once a day).

Patients with liver disease: The use of the drug in patients with liver disease has not been studied.

The drug should be taken for a long time, while continuing to follow the diet that the patient followed before starting treatment with Fenofibrat Canon.

Side effects

Side effects for therapeutic doses are given by frequency and system organ classification according to the WHO classification: very often -? 1/10 appointments (> 10%) often - from? 1/100 to <1/10 appointments (> 1% and 0.1% and <1%) rarely - from? 1/10000 to <1/1000 prescriptions (> 0.01% and From the digestive system: often - abdominal pain, nausea, vomiting, diarrhea and moderate flatulence

infrequently - cases of pancreatitis.

often - moderate increase in the concentration of serum transaminases infrequently - the formation of gallstones

och very rarely - hepatitis.

If symptoms of hepatitis (jaundice, itching) appear, laboratory tests should be performed and, if hepatitis is confirmed, fenofibrate should be canceled (see section "Special Instructions").

From the side of the musculoskeletal system and connective tissue: rarely - diffuse myalgia, myositis, muscle spasm and weakness

very rarely - rhabdomyolysis, increased activity of creatine phosphokinase (CPK).

Vascular disorders: infrequently - venous thromboembolism (pulmonary embolism, deep vein thrombosis).

From the circulatory and lymphatic systems: rarely - increased hemoglobin and white blood cells.

From the nervous system: rarely - sexual dysfunction, headache.

On the part of the respiratory system: very rarely - interstitial pneumopathy.

From the skin and subcutaneous fat: rarely a rash, itching, hives or photosensitivity reactions

rare - alopecia

very rare - photosensitization, accompanied by erythema, the formation of blisters or nodules in the skin, exposed to sunlight or artificial UV light (for example, a quartz lamp) in some cases (even after months of use without any complications).

Laboratory tests: infrequently - increased serum creatinine and urea concentrations.

Drug Interactions

Oral anticoagulants:

Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding due to the displacement of the anticoagulant from binding sites with blood plasma proteins.

At the beginning of treatment with fenofibrate, it is recommended to reduce the dose of anticoagulants by about a third, followed by a gradual selection of the dose. Dose selection is recommended to be carried out under the control of the level of INR (international normalized ratio).

cyclosporin: Several severe cases of reversible decline in renal function during simultaneous treatment with fenofibrate and cyclosporine have been described. Therefore, it is necessary to monitor the state of renal function in such patients and to cancel fenofibrate in the event of a serious change in laboratory parameters.

HMG-CoA reductase inhibitors (stats) and other fibrates:

When taking fenofibrate along with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases (see the section “Special Instructions”).

Isoenzymes of the P450 cytochrome system: In vitro studies of human liver microsomes have shown that fenofibrate and fenofibroic acid are not inhibitors of the following isoenzymes of cytochrome P450 (CYP3A4, CYP2D6, CYP2E1 or CYP1A2). At therapeutic concentrations, these compounds are weak inhibitors of the CYP2C19 and CYP2A6 isoenzymes and weak or moderate inhibitors of CYP2C9.

Overdose

Cases of overdose are not described. The specific antidote is unknown. If an overdose is suspected, symptomatic and, if necessary, supportive treatment should be prescribed. Hemodialysis is ineffective.

Storage conditions

In a dry, dark place at a temperature of no higher than 25 РC.

Keep out of the reach of children.

Expiration

2 years.

Deystvuyuschee substances

Fenofybrat

pharmacy

pharmacy terms

Form of Treatment

tablets

Kanonfarma, Russia