Ксеналтен® Ly

General characteristics. Structure:

Active ingredient: 120 mg of an orlistat in 1 capsule.

Excipients: cellulose microcrystallic, sodium carboxymethylstarch (sodium of starch glikolit), sodium lauryl sulfate, povidone.

Gelatinous solid capsules: the case and a lid of the capsule - titanium dioxide, dye blue patent, gelatin.

Pharmacological properties:

Pharmacodynamics. Orlistat is the specific and reversible inhibitor of gastrointestinal lipases possessing long action. Forms a covalent bond with

the active serinovy site of gastric and pancreatic lipases in a gleam of a stomach and small intestine. The inactivated enzyme loses ability to split the food fats arriving in the form of triglycerides (TG). Not split TG are not soaked up, and arising thereof reduction of receipt of calories in an organism leads to a body degrowth. Thus, therapeutic effect of drug is carried out without absorption in a system blood stream.

But to results of content of fat to Calais, action of an orlistat begins in 24-48 hours after reception. After drug withdrawal the content of fat in 48-72 hours usually is returned to Calais to the level taking place prior to therapy.

Orlistat is effective in respect of long control of body weight (decrease and maintenance of body weight, prevention of a repeated increase of body weight) at patients with the excess body weight or obesity. Treatment orlistaty leads to improvement of a profile of the risk factors and diseases accompanying obesity including a hypercholesterolemia, a diabetes mellitus 2 types, disturbance of tolerance to glucose, a giperinsulinemiya, arterial hypertension, and to reduction of amount of visceral fat.

Patients with obesity. In clinical trials at the patients accepting орлистат big loss of body weight in comparison with the patients who are on a dietotherapy was observed. Decrease in body weight began within the first 2 weeks after an initiation of treatment and continued from 6 to 12 months even at patients with the negative answer to a dietotherapy. For 2 years statistically significant improvement of a profile of the metabolic risk factors accompanying obesity was observed. Besides, in comparison with reception of placebo considerable reduction of amount of fat in an organism was noted. Orlistat is effective concerning prevention of a repeated increase of body weight. A repeated set of body weight, no more than 25% of lost, was observed approximately at a half of patients, and at a half of these patients of repeated set of body weight was not observed or even its further decrease was noted.

Patients with obesity and a diabetes mellitus 2 types. In clinical trials lasting from 6 months till 1 year at patients with the excess body weight or obesity and a diabetes mellitus 2 types accepting орлистат big loss of body weight in comparison with the patients undergoing treatment only a dietotherapy was observed. Loss of body weight happened generally due to reduction of amount of fat in an organism. It should be noted that prior to the research, despite reception of hypoglycemic means, at patients insufficient control of a glycemia was often noted. However when performing therapy orlistaty also clinically significant improvement of control of a glycemia was observed statistically. Besides, against the background of therapy orlistaty decrease in doses of hypoglycemic means, concentration of insulin, and also insulin resistance reduction was observed.

Reduction of risk of development of a diabetes mellitus 2 types at patients with obesity. In 4-year-old clinical trial it was shown what орлистат considerably reduces risk of development of a diabetes mellitus 2 types (approximately for 37% in comparison with placebo). Extent of reduction of risk was even more considerable at patients with initial disturbance of tolerance to glucose (approximately for 45%). In group of therapy orlistaty more considerable loss of body weight in comparison with group of placebo was noted. Maintenance of body weight at the new level was observed during the entire period of a research. Moreover, in comparison with placebo at the patients receiving therapy orlistaty considerable improvement of a profile of metabolic risk factors was observed.

Pubertal obesity. In clinical trials lasting 1 year at teenagers with obesity, at reception of an orlistat reduction of the body weight index (BWI), fatty weight, and also a circle of a waist and hips in comparison with group of placebo was observed. Also at the patients receiving therapy orlistaty considerable decrease in diastolic arterial pressure in comparison with group of placebo was noted.

Pharmacokinetics. Absorption. Absorption of an orlistat is minimum. After reception of therapeutic doses of an orlistat it was possible to reveal not changed орлистат in plasma only in rare instances, at the same time its concentration were extremely small (<10 ng/ml). Signs of cumulation were absent that confirms that absorption of an orlistat is minimum.

Distribution. The volume of distribution cannot be determined as орлистат it is very badly soaked up. In vitro орлистат more than for 99% contacts proteins of plasma, generally lipoproteins and albumine. Orlistat in the minimum quantity gets into erythrocytes.

Metabolism. Orlistat is metabolized mainly in an intestines wall with formation pharmacological of inactive metabolites of M1 (the hydrolyzed four-membered lactonic ring) and M3 (M1 with the chipped-off formylleucine N-rest). In a research at patients with obesity it is established that about 42% of that minimum fraction of an orlistat which is exposed to system absorption are the share of these two main metabolites.

Removal. The main way of removal is removal of not soaked up orlistat through intestines. Through intestines about 97% of the accepted dose of an orlistat, at the same time 83% - in the form of not changed orlistat were removed.

Total removal by kidneys of all metabolites makes less than 2% of the accepted dose. Orlistat and his metabolites of M1 and M3 are also exposed to removal through intestines. Time before full removal (kidneys and through intestines) makes 3-5 days. Removal of an orlistat was similar at patients with normal body weight and with obesity. Pharmacokinetics at special groups of patients

Plasma concentration of an orlistat and its metabolites (M1 and M3) at children do not differ from those at adults when comparing identical doses of drug. Daily excretion of fat through intestines makes 27% of reception with food at therapy of orlistaty and 7% - at placebo reception.

Indications to use:

Long therapy of patients with obesity (IMT> of 30 kg/sq.m) or patients with the excess body weight (IMT> of 28 kg/sq.m), including having the risk factors associated with obesity, in combination with it is moderated by a hypocaloric diet.

In a combination with hypoglycemic drugs (Metforminum, derivatives of sulphonylurea and/or insulin) or moderately hypocaloric diet at patients with a diabetes mellitus 2 types with the excess body weight or obesity.

Route of administration and doses:

Inside, with each main meal (during food or not later than in 1 hour after food), washing down with water. If meal is missed or if food does not contain fat, then administration of drug KSENALTEN LOGO can also be missed.

Drug KSENALTEN LOGO should be accepted in a combination to the balanced, moderately hypocaloric diet containing no more than 30% of a kalorazh in the form of fats. Daily consumption of fats, carbohydrates and proteins needs to be distributed on three main meals.

Long therapy of patients with obesity (IMT> of 30 kg/sq.m) or patients with the excess body weight (IMT> of 28 kg/sq.m), including having the risk factors associated with obesity, in combination with it is moderated by a hypocaloric diet: at adults and children 12 years the recommended dose of an orlistat are more senior makes 120 mg (1 capsule) 3 times a day with each main reception beggars or not later than in 1 hour after food.

In a combination with ginoglikemichesky drugs or moderately hypocaloric diet at patients with a diabetes mellitus 2 types from a log hut the exact body weight or obesity: at adults the recommended dose of an orlistat makes 120 mg (1 capsule) 3 times a day with each main reception write or not later than in 1 hour after food.

Increase in a dose of an orlistat over recommended (120 mg 3 times a day) does not lead to strengthening of its therapeutic effect.

Efficiency and safety of drug KSENALTEN LOGO at patients with an abnormal liver function and/or kidneys, and also at patients of advanced and children's age (12 years are younger) were not investigated.

Features of use:

Pregnancy and period of breastfeeding. Children's age up to 12 years. With care: Simultaneous use with cyclosporine, Amiodaronum, antiepileptic drugs, sodium left thyroxine, warfarin or other peroral aptikoagulyanta, age up to 18 years.

Pregnancy and lactation: use of an orlistat is contraindicated during pregnancy due to the lack of the reliable clinical data confirming safety of its use.

Penetration of an orlistat into breast milk was not studied therefore its use is contraindicated during breastfeeding. In need of use of drug during breastfeeding, feeding by a breast should be stopped.

During treatment it is necessary to keep to the balanced, low-calorie diet containing no more than 30% of a kalorazh in the form of fats and enriched with fruit and vegetables.

Daily consumption of fats, carbohydrates and proteins needs to be distributed on three main meals.

The probability of emergence of undesirable reactions from digestive tract increases at use of an orlistat with the food containing a large amount of fats (more than 30% of daily caloric content). In clinical trials during 4 years of therapy orlistaty remained with most of patients of concentration of vitamins A, D, E, K and beta carotene normal. It is possible to apply polyvitamins to ensuring adequate intake of mineral substances and vitamins.

As decrease in body weight usually is followed by improvement of indicators of carbohydrate metabolism, patients with a diabetes mellitus 2 types have to consult with the doctor if necessary to correct a dose of hypoglycemic drugs.

Decrease in body weight at treatment can be followed by a lowering of arterial pressure and concentration of cholesterol. The patients accepting drugs for treatment of arterial hypertension and a hypercholesterolemia have to consult with the doctor if necessary to correct doses of the above-stated drugs.

Though interaction between orlistaty and oral contraceptives was not observed, орлистат can reduce indirectly a biodostuppost of peroralpy contraceptives that can lead to development of undesirable pregnancy. It is recommended to use additional types of contraception in case of development of acute diarrhea.

Simultaneous use of an orlistat with Amiodaronum, antiepileptic drugs, sodium left thyroxine, warfarin or other peroral anticoagulants perhaps only after consultation with the doctor (see the section "Interaction with Other Medicines").

Use of an orlistat along with cyclosporine or acarbose is not recommended and demands consultation with the doctor.

To patients with diseases of kidneys, before reception of an orlistat it is necessary to consult with the doctor as development of a giperoksalaturiya and nephropathy is possible.

Patients should stop reception of an orlistat and to see a doctor in case of such symptoms as icteric coloring of a sclera or skin, darkening of urine and loss of appetite.

Influence on ability to manage vehicles and mechanisms. Orlistat does not exert impact on ability to manage vehicles and to perform the work requiring special attention and speed of psychomotor reactions. Patients 2 types applying орлистат in a combination with hypoglycemic drugs have to be careful with a diabetes mellitus at control of vehicles and mechanisms in connection with possible development of the hypoglycemia which is followed by dizziness, a vision disorder.

Side effects:

Undesirable reactions at use of an orlistat arose mainly from digestive tract and were caused by pharmacological action of the orlistat interfering absorption of fats of food.

Frequency of emergence of undesirable reactions is presented as follows: very often (> 1/10 cases), it is frequent (> 1/100 and <1/10 cases), infrequently (> 1/1000 and <1/100 cases), is rare (> 1/10000 and <1/1000 cases) and is very rare (<1/10000 cases).

Disturbances from digestive tract: very often - oily allocations from a rectum, a passage of flatus with a quantity separated, imperative desires on defecation, a steatorrhea, defecation increase, a liquid chair, a meteorism, pains or discomfort in a stomach.

As a rule, the specified undesirable reactions are slight and tranzitorny, arise in the first three months. Frequency of these undesirable reactions increases at increase in content of fat in food. Patients should be informed on possibility of the specified undesirable reactions and to train how to eliminate them by the best observance of a diet, especially concerning amount of the fat which is contained in it.

Often - abdominal distention, a "soft" chair, pains or discomfort in a rectum, an incontience a calla, damage of teeth, damage of gums.

Disturbances from a nervous system: very often - headaches.

Disturbances from respiratory system, bodies of a thorax and a mediastinum: very often - upper respiratory tract infections; often - lower respiratory tract infections.

Disturbances from kidneys and urinary tract: often - infections of urinary tract.

Disturbances from immune system: seldom - hypersensitivity reactions (an itch, urticaria, rash, a Quincke's disease, a bronchospasm, an anaphylaxis).

Disturbances from skin and hypodermic fabrics: very seldom - violent rash. Disturbances from a liver and biliary tract: very seldom - hepatitis (relationship of cause and effect is not established with reception of an orlistat).

Disturbances from generative organs and a mammary gland: often - a dysmenorrhea. Laboratory and tool data: very seldom - increase in activity of transaminases and an alkaline phosphatase.

Disturbances from a metabolism and food: very often - a hypoglycemia (patients with a diabetes mellitus have 2 types).

Disturbances of mentality: often - alarm.

Infectious and parasitic diseases: very often - flu.

The general frustration and disturbances in an injection site: often - weakness.

Also in the post-marketing period cases of spasms (are registered at simultaneous use with antiepileptic drugs), decrease in a prothrombin, increase in MNO (at simultaneous use with anticoagulants), rectal bleeding, a diverticulitis, pancreatitis, a cholelithiasis and an oxalic nephropathy (frequency of emergence is unknown).

Patients with a diabetes mellitus have 2 types character and frequency of the undesirable phenomena were comparable to those at persons without sugar diabeg with the excess body weight and obesity. The only new by-effects at patients with a diabetes mellitus 2 types were the hypoglycemic states arising with a frequency> 2% and incidence> in 1% but to comparison with placebo (which could result from improvement of compensation of carbohydrate metabolism), and is frequent - abdominal distention.

In 4-year-old clinical trial the general profile of safety did not differ from that, received in 1-and 2-year researches. At the same time the general frequency of emergence of the undesirable phenomena from digestive tract annually decreased throughout the 4-year period of administration of drug.

If any of the undesirable reactions specified in the instruction are aggravated, or you noticed other undesirable reactions which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

At a concomitant use of an orlistat and cyclosporine decrease in concentration of cyclosporine in a blood plasma therefore more frequent definition of concentration of cyclosporine in a blood plasma at a concomitant use of an orlistat and cyclosporine is recommended was noted. In case of simultaneous use of an orlistat and cyclosporine continuous monitoring of concentration of cyclosporine in a blood plasma as decrease in its plasma concentration is possible is necessary.

Simultaneous use of an orlistat and acarbose, due to the lack of data on pharmacokinetic interactions is not recommended.

At simultaneous use of an orlistat and anticoagulants cases of decrease in a prothrombin, increase in values of the international normalized relation (INR) and unbalanced therapy are registered by anticoagulants that led to change of haemo static parameters. Therefore at simultaneous use of warfarin or other indirect anticoagulants with orlistaty control of indicators of MNO is necessary.

At a concomitant use with orlistaty absorption of fat-soluble vitamins A, D, E and K decreases. If polyvitamins are recommended, it is necessary to accept them not less than in 2 h after reception of an orlistat or before going to bed.

At simultaneous use of Amiodaronum with orlistaty decrease in system exposure of Amiodaronum and dezetilamiodaron, however in connection with difficult pharmacokinetics of Amiodaronum was noted, the clinical importance of this phenomenon is not clear. At simultaneous use of an orlistat with Amiodaronum clinical observation of the patient and monitoring of the electrocardiogram is recommended.

At simultaneous use of an orlistat and antiepileptic drugs cases of development of spasms were observed. Relationship of cause and effect between development of spasms and therapy orlistaty is not established. Nevertheless, it is necessary to monitorirovat a condition of patients regarding possible changes in frequency and/or weight of a convulsive syndrome.

At simultaneous use of an orlistat with left thyroxine of sodium the hypothyroidism and/or decrease in control of a hypothyroidism can develop that can be connected with reduction of absorption of inorganic iodine and/or left thyroxine of sodium.

Interaction of an orlistat with amitriptyline, atorvastatiny is not revealed. guanyl guanidines, digoxin, fibrata, fluoxetine, lozartany, Phenytoinum, oral contraceptives, phentermine, pravastatiny, nifedipine, sibutraminy and ethanol.

In some cases орлистат can reduce in the indirect way bioavailability of oral contraceptives. In case of diarrhea use of an additional method of contraception is recommended.

Contraindications:

Hypersensitivity to an orlistat or other components of drug.

Syndrome of chronic malabsorption.

Cholestasia.

Abnormal liver function, renal failure (efficiency and safety are not studied).

Simultaneous use with acarbose is not recommended.

Overdose:

The single dose in 800 mg of an orlistat or at its use in a dose to 400 mg three times a day within 15 days by people with normal body weight and with obesity was not followed by the significant undesirable phenomena. Besides, patients with obesity have an experience of use of an orlistat on 240 mg 3 times a day within 6 months that was not followed by reliable increase in frequency of the undesirable phenomena.

In cases of overdose of an orlistat it was reported or about lack of the undesirable phenomena, or the undesirable phenomena did not differ from those. which are observed at use of drug in therapeutic doses.

In case of overdose it is necessary to see a doctor. At the expressed overdose of an orlistat, it is necessary to watch a condition of the patient during 24 h. According to researches at the person and animals, any system effects which can be connected with lipazoingibiruyushchy properties of an orlistat have to be quickly reversible.

Storage conditions:

In the dry place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Capsules of 120 mg. Packaging: on 7 or 21 capsule in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 4 blister strip packagings together with the application instruction in a pack from a cardboard.