Fenofibrate Canon 145 mg, 30 pcs.

1 tab .:

- fenofibrate 145 mg

Excipients:

corn starch - 137 mg,

colloidal silicon dioxide - 10 mg,

croscarmellose sodium - 33 mg,

mannitol - 170 mg,

magnesium stearate - 6 mg,

povidone K-30 - 44 mg,

microcrystalline cellulose - 105 mg.

Film casing composition:

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

macrogol - 4.72 mg,

talc - 3.48 mg,

titanium dioxide - 2.42 mg.

Pharmaceutical group:

  Lipid-lowering drug.

Pharmaceutical action:

  By activating PPAR-alpha (alpha receptors activated by the peroxisome proliferator), fenofibrate enhances lipolysis and excretion of atherogenic lipoproteins with a high triglyceride content from blood plasma by activating lipoprotein lipase and reducing the synthesis of apoproteins CIII. The activation of PPAR-alpha also leads to an increase in the synthesis of apoproteins AI and AII.

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

In addition, by correcting violations of the synthesis and catabolism of VLDL, fenofibrate increases the clearance of LDL and reduces the content of dense and small size LDL particles, an increase in which is observed in patients with atherogenic lipid phenotype, a frequent disorder in patients at risk of coronary heart disease. In the course of clinical studies, it was noted that the use of fenofibrate reduces the concentration of total cholesterol by 20-25% and triglycerides by 40-55% while increasing the concentration of HDL-cholesterol by 10-30%. In patients with hypercholesterolemia, in whom 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 accompanied and not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, for example, in type 2 diabetes mellitus. During treatment with fenofibrate, extravascular cholesterol deposits (tendon and tuberous xanthomas) can be significantly reduced and even completely disappeared. In patients with elevated fibrinogen levels treated with fenofibrate, a significant decrease in this indicator was noted, as well as in patients with elevated lipoprotein levels. Other markers of inflammation, such as C-reactive protein, are also reduced with fenofibrate treatment.

For patients with dyslipidemia and hyperuricemia, an additional benefit is the uricosuric effect of fenofibrate, resulting in a decrease in uric acid concentration by about 25%.

In a clinical study and in animal experiments, it has been shown that fenofibrate reduces platelet aggregation caused by adenosine diphosphate, arachidonic acid and epinephrine.

Pharmacokinetics: 

The drug Fenofibrate Canon in the form of micronized fenofibrate has a higher bioavailability.
The original fenofibrate is not detected in blood plasma. The main plasma metabolite is fenofibric acid.

Absorption: 
Cmax is achieved 4-5 hours after oral administration. With prolonged use, the concentration of the drug in the blood plasma remains stable. The absorption of fenofibrate is enhanced when taken with food.

Distribution: 
fenofibric acid strongly binds to blood plasma albumin (more than 99%).
Half-life: T1 / 2 of fenofibric acid - about 20 hours.

Metabolism and excretion: 
only the main metabolite of fenofibrate, fenofibric acid, is found in blood plasma. Fenofibrate is not a substrate for the CYP3A4 isoenzyme. Does not take part in microsomal metabolism.

It is excreted mainly by the kidneys in the form of fenofibric acid and glucuronide konyogate. Within 6 days, fenofibrate is eliminated almost completely. The total clearance of fenofibric acid measured in elderly patients does not change.
The drug does not accumulate after a single dose and with prolonged use. It is not excreted during hemodialysis.

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

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

- in order to reduce the increased concentration of LDL, total cholesterol, triglycerides and ApoB (apolipoprotein B) and increase the concentration of HDL in patients with primary hyperlipidemia or mixed dyslipidemia (type IIa, IIb, III, IV according to Fredrickson).

- hypersensitivity to fenofibrate or other components of the drug;
- liver failure (including biliary cirrhosis and persistent liver dysfunction of unknown etiology);
- severe renal failure (creatinine clearance <20 ml / min);
- age up to 18 years (efficacy and safety have not been established);
- a history of photosensitization or phototoxicity during treatment with fibrates or ketoprofen;
- history of gallbladder disease;
- period of breastfeeding;
- chronic or acute pancreatitis, with the exception of cases of acute pancreatitis due to severe hypertriglyceridemia.

With caution: with hypothyroidism; alcohol abuse patients; patients with impaired renal function (CC more than 20 ml / min); elderly, with a history of hereditary muscle diseases; while taking oral anticoagulants, HMG-CoA reductase inhibitors (see the section "Interaction with other medicinal products").

Side effects for therapeutic doses are given by frequency and system-organ classes 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 appointments (> 0.01% and From the digestive system:
often - abdominal pain, nausea, vomiting, diarrhea and moderate flatulence;
infrequently - cases of pancreatitis .
often - a moderate increase in the concentration of serum transaminases, rarely - the formation of gallstones;
very rarely - hepatitis.

If symptoms of hepatitis appear (jaundice, pruritus), laboratory tests should be carried out and, if hepatitis is confirmed, fenofibrate should be discontinued. (see the section "Special instructions").

From 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).

On the part of the circulatory and lymphatic system:
rarely - an increase in hemoglobin and leukocytes.

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

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

On the part of the skin and subcutaneous fat:
infrequently, rash, pruritus, urticaria or photosensitivity reactions;
rarely - alopecia;

very rarely - photosensitization, accompanied by erythema, blistering or nodules on skin areas exposed to sunlight or artificial UV light (for example, a quartz lamp) in some cases (even after many months of use without any complications).

Laboratory tests:
infrequently - an increase in the concentration of creatinine and urea in the blood serum.

Oral anticoagulants:

Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of the anticoagulant from the sites of binding to 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. The dose selection is recommended to be carried out under the control of the INR level (international normalized ratio).

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

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

When fenofibrate is taken concurrently with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases (see section "Special instructions").

Cytochrome P450 isozymes:

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

The tablets should be swallowed whole, without chewing, at the same time with food intake.

Adults:
One tablet once a day. Patients taking one 200 mg fenofibrate capsule can switch to one Fenofibrate Canon 145 mg tablet without further dose adjustment. The maximum daily dose is 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 adhered to before starting treatment with Fenofibrate Canon.

Overdose cases 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.

Before starting treatment with Fenofibrate Canon, appropriate treatment should be carried out 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 assessed 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 advisability of prescribing 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 the hyperlipidemia is of a primary or secondary nature. In such cases, the increase in lipid levels can be caused by the intake of estrogens.

Liver function: When taking fenofibrate and other drugs that lower lipid concentrations, an increase in the activity of "hepatic" transaminases has been described in some patients. 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 concentrations of transaminases during treatment require attention, and if the concentration of ALT and ACT is more than 3 times higher than the upper limit of the norm, they stop taking the drug.

Pancreatitis: Cases of pancreatitis have been described during treatment with fenofibrate. Possible causes of pancreatitis in these cases were: insufficient drug efficacy in patients with severe hypertriglyceridemia, direct drug exposure, as well as secondary events associated with the presence of stones or the formation of sediment in the gallbladder, accompanied by obstruction of the common bile duct.

Muscle: Muscle toxicity has been reported with fenofibrate and other lipid-lowering drugs, including very rare cases of rhabdomyolysis. The incidence of this disorder is increased in the case of hypoalbuminemia and a history of renal failure. The possibility of this complication increases in cases of hypoalbuminemia and renal failure.

A 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 creatinine phosphokinase (CPK) activity (more than 5 times compared to the upper limit of the norm). In these cases, treatment with fenofibrate should be discontinued.

The risk of developing rhabdomyolysis may increase in patients with a predisposition to myopathy and / or rhabdomyolysis, including age over 70 years, a history of hereditary muscle diseases, impaired renal function, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit outweighs the possible risk of developing rhabdomyolysis. When taking the drug Fenofibrate Canon simultaneously 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 starting treatment. In this regard, the joint appointment of the drug Fenofibrate Canon and statutes is permissible only if the patient has severe mixed dyslipidemia and high cardiovascular risk,

Renal function: When using the drug Fenofibrate Canon as monotherapy or in combination with statins, patients have a reversible increase in serum creatinine concentration. The increase in creatinine concentration, in general, was stable over time with no signs of further increase in serum creatinine concentration with prolonged therapy, with a tendency to return to initial values ​​after discontinuation of treatment. The clinical significance of these observations has not been established. In patients with renal insufficiency, it is recommended to monitor renal function while taking Fenofibrate Canon. Monitoring of renal function should be carried out in patients at risk of developing renal failure, namely in elderly patients and patients with diabetes mellitus. Treatment should be canceled if the creatinine concentration increases> 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 termination.

Influence on the ability to drive a car and other mechanisms:

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