Traykor

General characteristics. Structure:

Active agent: фенофибрат (micronized) 145 mg

Excipients: sucrose — 145 mg; sodium lauryl sulfate — 10,2 mg; lactoses monohydrate — 132 mg; кросповидон — 75,5 mg; MKTs — 84,28 mg; silicon dioxide colloid — 1,72 mg; a gipromelloza — 29 mg; sodium docusate — 2,9 mg; magnesium stearate — 0,9 mg 
 
Cover (Opadry® OY-B-28920): 25,1 mg (polyvinyl alcohol — 11,43 mg; titanium dioxide — 8,03 mg; talc — 5,02 mg; lecithin soy — 0,5 mg; gum xanthane — 0,12 mg).

Active agent: фенофибрат 160 mg

Excipients: sodium lauryl sulfate — 5,6 mg; lactoses monohydrate — 138,4 mg; povidone — 160 mg; кросповидон — 96 mg; MKTs — 115 mg; silicon dioxide colloid — 12,6 mg; the sodium stearylfumarating — 6,4 mg  

Cover (Opadry® OY-B-28920): 28 mg (polyvinyl alcohol — 12,75 mg; titanium dioxide — 8,96 mg; talc — 5,6 mg; lecithin soy — 0,56 mg; gum xanthane — 0,13 mg).

Pharmacological properties:

Pharmacodynamics. Fenofibrat is derivative fibroyevy acid which ability to change the maintenance of lipids in a human body, is mediated by activation of PPARα. Activating PPARα receptors (the alpha receptors activated by a proliferator of peroxisomas), фенофибрат strengthens a lipolysis and removal from plasma of atherogenous lipoproteins with the high content of triglycerides by activation of lipoproteinlipase and reduction of synthesis of apolipoprotein CIII. Activation of PPARα also leads to strengthening of synthesis of AI and AII apolipoproteins.
The effects of a fenofibrat described above on lipoproteins lead to reduction of maintenance of LPNP and LPONP fraction to which number apolipoprotein B, and to increase in maintenance of LPVP fraction to which number AI and AII apolipoproteins belong belongs.
Besides, due to correction of disturbances of synthesis and a catabolism of LPONP, фенофибрат increases clearance of LPNP and reduces contents dense and the small particle size LPNP which increase is observed at patients with an atherogenous phenotype of lipids (frequent disturbance at patients with risk of an ischemic heart disease).
During clinical trials it was noted that use of a fenofibrat reduces the level of the general cholesterol by 20–25% and triglycerides for 40–55% at increase in level of LPVP-cholesterol for 10–30%. At patients with a hypercholesterolemia at whom the level of LPNP-cholesterol decreases by 20–35% use of a fenofibrat led to decrease in ratios: "the general cholesterol / ЛПВП-холестерин", "LPNP-holesterin/LPVP-holesterin" and "Apo In / Apo of AI", being markers of atherogenous risk.
Considering influence of a fenofibrat on the LPNP-cholesterol level and triglycerides, use of drug is effective at patients with the hypercholesterolemia which both is followed, and which is not followed by a gipertriglitseridemiya including a secondary giperlipoproteinemiya, for example at a diabetes mellitus of type 2.
During treatment fenofibraty can decrease considerably and even completely to disappear extravasated deposits of cholesterol (tendinous and tuberous xanthomas).
At the patients with the increased level of fibrinogen who received treatment fenofibraty considerable decrease in this indicator as well as at patients with the increased Lp (a) level is noted. Other markers of an inflammation, such as S-reactive protein, also decrease at treatment fenofibraty.
For patients with a dislipidemiya and a hyperuricemia the additional benefit consists in the uricosuric effect of a fenofibrat leading to decrease in concentration of uric acid approximately by 25%.
During clinical trial and in experiments on animals it was shown what фенофибрат reduces the aggregation of thrombocytes caused by adenosinediphosphate, arachidonic acid and Epinephrinum.

Pharmacokinetics. Трайкор® 145 mg of a tablet, film coated, contain 145 mg of the micronized fenofibrat in the form of nanoparticles.
Initial фенофибрат in plasma it is not found. The main plasma metabolite is fenofibroyevy acid.
Cmax in a blood plasma is reached in 2–4 h after intake. At prolonged use concentration of drug in plasma remains stable, irrespective of specific features of the patient.
Unlike the previous dosage forms of a fenofibrat, the maximum concentration in a blood plasma and the systemic effect of a fenofibrat in the form of nanoparticles does not depend on meal. Therefore Трайкор® 145 mg can be accepted irrespective of meal at any time.
Fenofibroyevy acid strongly contacts plasma albumine (more than 99%).
T1/2 of fenofibroyevy acid is about 20 h.
After use inside фенофибрат it is quickly hydrolyzed by esterases. In plasma only the main active metabolite of a fenofibrat — fenofibroyevy acid is found. Fenofibrat is not substrate for CYP3A4. Does not take part in microsomal metabolism.
It is removed mainly with urine in the form of fenofibroyevy acid and a conjugate of a glucuronide. Within 6 days фенофибрат it is removed almost completely. The general clearance of fenofibroyevy acid defined at elderly patients does not change.
Drug does not kumulirutsya after a single dose and at prolonged use.
At a hemodialysis it is not removed.
Трайкор® 160 mg of a tablet, film coated, have higher bioavailability in comparison with earlier dosage forms of a fenofibrat.
Initial фенофибрат in plasma it is not found. The main plasma metabolite is fenofibroyevy acid.
Cmax in a blood plasma is reached in 4–5 h after intake. At prolonged use concentration of drug in plasma remains stable. Absorption of a fenofibrat amplifies at a concomitant use with food.
Fenofibroyevy acid strongly contacts plasma albumine (more than 99%).
T1/2 of fenofibroyevy acid is about 20 h.
In plasma only the main metabolite of a fenofibrat — fenofibroyevy acid is found. It is removed mainly with urine in the form of fenofibroyevy acid and a conjugate of a glucuronide. Within 6 days фенофибрат it is removed almost completely. The general clearance of fenofibroyevy acid defined at elderly patients does not change.
Drug does not kumulirutsya after a single dose and at prolonged use.
At a hemodialysis it is not removed.

Indications to use:

the hypercholesterolemia and gipertriglitseridemiya isolated or mixed (a dislipidemiya the type IIa, IIb, III, IV, V) (the tab. of 145 mg) and (a dislipidemiya the type IIa, IIb, III, IV, V) (the tab. of 160 mg) at patients for whom the diet or other non-drug medical actions (for example decrease in body weight or increase in physical activity) were inefficient, especially with the risk factors connected with a dislipidemiya, such as arterial hypertension and smoking;

secondary giperlipoproteinemiya when the giperlipoproteinemiya remains despite effective treatment of a basic disease (for example a dislipidemiya at a diabetes mellitus).

At drug Traykor® use patients should adhere to a diet to which they kept prior to treatment.

Route of administration and doses:

Inside, swallowing entirely, not chewing, washing down with a glass of water, at any time, irrespective of meal (the tab. of 145 mg) and along with meal (the tab. of 160 mg).

The adult, according to 1 tab. of 1 times a day. The patients accepting on 1 капс. Lipantila 200 M or according to 1 tab. of Трайкора® 160 mg/days, can pass to reception 1 tab. of Трайкора® 145 mg without additional correction of a dose. The patients accepting on 1 капс. Lipantila 200 M a day, can pass to reception 1 tab. of Трайкора® 160 mg without additional correction of a dose.

To elderly patients: it is recommended to accept a standard dose for adults (according to 1 tab. Трайкора® 1 of times a day).

Patients with a renal failure need a dose decline (see the section "Special Instructions").

Use of drug for patients with diseases of a liver is not studied.

Drug it is necessary to accept a long time, at the same time continuing to keep to a diet to which the patient adhered prior to treatment of Traykorom®. Efficiency of treatment by drug has to be estimated by the doctor periodically.

Efficiency of therapy should be estimated on the maintenance of lipids (the general cholesterol, LPNP, triglycerides) in blood serum. In the absence of therapeutic effect after several months of therapy (as a rule, after 3 months) it is necessary to consider expediency of purpose of the accompanying or alternative therapy.

Features of use:

Before starting treatment of Traykorom®, it is necessary to carry out the corresponding treatment for elimination of the reason of a secondary hypercholesterolemia, for example at such states and diseases as an uncontrollable diabetes mellitus of type 2, a hypothyroidism, a nephrotic syndrome, a disproteinemia, obstructive diseases of a liver, an effect of medicamentous therapy, alcoholism.

Efficiency of therapy should be estimated on the maintenance of lipids (the general cholesterol, LPNP, triglycerides) in blood serum. In the absence of therapeutic effect after several months of therapy (as a rule after 3 months) it is necessary to consider expediency of purpose of the accompanying or alternative therapy.

It is necessary to find out from the patients with a lipidemia accepting the estrogen or hormonal contraceptives containing estrogen whether the lipidemia has primary or secondary nature. In such cases increase in level of lipids can be caused by reception of estrogen.

Function of a liver: at reception of Traykora® and other drugs reducing concentration of lipids at some patients increase in level of hepatic transaminases is described. In most cases such increase was temporary, insignificant and asymptomatic. Within the first 12 months of treatment it is recommended to control the level of transaminases (ALT, nuclear heating plant) every 3 month. Patients at whom against the background of treatment concentration of transaminases increased require attention, and in case of increase in concentration of ALT and nuclear heating plant more than by 3 times in comparison with the upper bound of norm, stop administration of drug.

Pancreatitis: cases of development of pancreatitis during treatment of Traykorom® were described. The possible reasons of pancreatitis in these cases were: insufficient efficiency of drug at patients with a heavy gipertriglitseridemiya, direct influence of drug, and also the secondary phenomena connected with existence of the stones or formation of a deposit in a gall bladder which are followed by impassability of the general bilious channel.

Muscles: at reception of Traykora® and other drugs reducing concentration of lipids cases of toxic influence on muscular tissue, including very exceptional cases of a rabdomioliz are described. Frequency of such disturbance increases in case of a hypoalbuminemia and a renal failure in the anamnesis. Possibility of this complication increases in cases of a hypoalbuminemia and a renal failure.

Toxic influence on muscular tissue can be suspected on the basis of complaints of the patient to weakness, a diffusion mialgiya, a miositis, muscular spasms and spasms and/or the expressed increase in activity of a kreatinfosfokinaza (more than by 5 times in comparison with the upper bound of norm). In these cases treatment of Traykorom® needs to be stopped.

The risk of development of a rabdomioliz can increase at patients with predisposition to a myopathy and/or a rabdomioliz, including age 70 years, the burdened anamnesis on hereditary muscular diseases, a renal failure, a hypothyroidism, an alcohol abuse are more senior. Such patients should appoint drug only if the expected advantage exceeds possible risk of development of a rabdomioliz.

At reception of Traykora® along with inhibitors of GMG-KOA-reduktazy or other fibrata the risk of serious toxic impact on muscle fibers, especially, increases if the patient prior to treatment had a disease of muscles. In this regard joint purpose of Traykora® and statine is admissible only in the presence at the patient of the heavy mixed dislipidemiya and high cardiovascular risk, in the absence of a disease of muscles in the anamnesis and in the conditions of the fixed control directed to identification of signs of development of toxic influence on muscular tissue.

Renal function: in case of increase in concentration of creatinine treatment more than 50% higher than the upper bound of norm should be suspended. In the first 3 months of treatment it is recommended to define concentration of creatinine.

At use of drug influence on ability to driving by the car and to control of mechanisms was not noted.

Side effects:

Frequency of the side reactions given below was defined as follows: very often (≥1/10), it is frequent (> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages.

From a GIT: often — an abdominal pain, nausea, vomiting, diarrhea and a meteorism of moderate weight; sometimes — pancreatitis cases.

From a liver: often — moderate increase in concentration of serumal transaminases; sometimes — formation of gallstones; very seldom — hepatitis episodes. At emergence of symptoms of hepatitis (jaundice, an itch) it is necessary to conduct laboratory researches and, in case of confirmation of hepatitis, to cancel фенофибрат. (See. "Special instructions").

From skeletal and muscular system and connecting fabric: seldom — a diffusion mialgiya, a miositis, muscular spasms and weakness; very seldom — рабдомиолиз (an acute necrosis of skeletal muscles).

Vascular disorders: sometimes — a venous thromboembolism (a pulmonary embolism, a deep vein thrombosis).

From circulatory and lymphatic system: seldom — increase in a hemoglobin content and leukocytes.

From a nervous system: seldom — sexual dysfunction, a headache.

From a respiratory organs: very seldom — intersticial pneumopathies.

From skin and a hypodermic fatty tissue: sometimes — rash, an itch, urticaria or reactions of a photosensitivity; seldom — an alopecia; very seldom — the photosensitization which is followed by an erythema, blistering or small knots on the sites of skin subjected to impact of a sunlight or artificial UF-radiation, for example a quartz lamp (in some cases — after months-long use without any complications).

Laboratory researches: sometimes — increase in level of creatinine and urea in serum.

Interaction with other medicines:

Peroral anticoagulants: фенофибрат strengthens effect of peroral anticoagulants and can increase risk of bleedings that it is connected with replacement of anticoagulant from places of linkng with proteins of a blood plasma.

In an initiation of treatment fenofibraty it is recommended to lower a dose of anticoagulants approximately on a third with the subsequent gradual selection of a dose. Selection of a dose is recommended to be carried out under control of the MNO level.

Cyclosporine: several hard cases of reversible decrease in renal function are described during simultaneous treatment fenofibraty and cyclosporine. Therefore it is necessary to control a condition of renal function at such patients and to cancel фенофибрат in case of serious change of laboratory parameters.

Inhibitors of GMG-KOA-reduktazy and other fibrata: at reception of a fenofibrat along with inhibitors of GMG-KOA-reduktazy or other fibrata the risk of serious toxic impact on muscle fibers increases (see the section "Special Instructions").

P450 cytochrome enzymes: researches of microsomes from a liver of the person of in vitro showed that фенофибрат and fenofibroyevy acid are not inhibitors of the following isoenzymes of P450 cytochrome: CYP3A4, CYP2D6, CYP2E1 or CYP1A2. In therapeutic concentration these connections are weak inhibitors of isoenzymes of CYP2C19 and CYP2A6 and weak or moderate CYP2C9 inhibitors.

Contraindications:

- hypersensitivity to a fenofibrat or other HP components;
- a heavy liver failure (including cirrhosis);
- heavy renal failure (creatinine Cl <20ml/mines);
- age up to 18 years;
- existence in the anamnesis of a photosensitization or phototoxicity at treatment of a fibratama or ketoprofen;
- diseases of a gall bladder;
- breastfeeding period;
- an inborn galactosemia, insufficiency of lactase, disturbance of absorption of glucose and a galactose (drug contains lactose);
- an inborn fruktozemiya, insufficiency of invertase-isomaltase (drug contains sucrose) (the tab. of 145 mg);
- allergic reaction to a peanut, peanut butter, soy lecithin or related products in the anamnesis (in connection with risk of development of reaction of hypersensitivity).

With care:
- liver and/or renal failure;
- hypothyroidism;
- the patients abusing alcohol;
- patients of advanced age;
- patients with the burdened anamnesis on hereditary muscular diseases;
- a concomitant use of peroral anticoagulants, GMG-KOA-reduktazy inhibitors (see the section "Interaction").

Use at pregnancy and feeding by a breast
There are not numerous data on use of a fenofibrat by pregnant women. In experiments on animals the teratogenic effect of a fenofibrat was not observed. Embriotoxity was noted at appointment during preclinical tests of doses, toxic for a maternal organism. The potential risk for the person is unknown. Therefore during pregnancy of the tablet Traykor® can be applied only after careful assessment of a ratio of risk and advantage.

Due to the lack of data on safety of use drug is contraindicated to use during breastfeeding.

Overdose:

Cases of overdose are not described. The specific antidote is unknown. At suspicion it is necessary to appoint to overdose symptomatic and, if necessary, the supporting treatment.

The hemodialysis is inefficient.

Storage conditions:

In the dry place, at a temperature not above 25 °C in not opened original packing.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

In the blister of 10 pieces; in a pack of cardboard 1, 2, 3, 5, 9 and 10 blisters; or in the blister of 14 pieces; in a pack of cardboard 2, 6 and 7 blisters; or in the blister of 10 pieces; in a box of cardboard 28 and 30 blisters (for hospitals).

In the blister of 10 pieces; in a pack of cardboard 1, 2, 3, 5, 9 and 10 blisters; or in the blister of 14 pieces; in a pack of cardboard 2, 6 and 7 blisters.