Listata tablets p / o 120mg, No. 80

long-term therapy of obese patients with a BMI of at least 30 kg / m2 or overweight patients with a BMI of at least 28 kg / m2, incl. having risk factors associated with obesity, in combination with a moderately hypocaloric diet;

in combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and / or insulin) and / or a moderately hypocaloric diet in patients with type 2 diabetes mellitus who are overweight or obese.

Inside with water.

Treatment of obese patients with a BMI of at least 30 kg / m2 or overweight patients with a BMI of at least 28 kg / m2, incl. having risk factors associated with obesity, in combination with a moderately hypocaloric diet: for adults and children over 12 years of age - the recommended dose of Listat is 1 table. (120 mg) with each main meal (with meals or no later than 1 hour after meals).

In combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and / or insulin) and / or a moderately hypocaloric diet in patients with type 2 diabetes mellitus with overweight or obesity: for adults - the recommended dose of Listat is 1 table. (120 mg) with each main meal (with meals or no later than 1 hour after meals).

If the meal is skipped or the food does not contain fat, then you can also skip taking Listat.

Listat should be taken in conjunction with a balanced, moderately hypocaloric diet containing no more than 30% of calories as fat. The daily intake of fats, carbohydrates and proteins should be split between 3 main meals.

An increase in the dose of Listata over the recommended dose (120 mg 3 times a day) does not lead to an increase in its therapeutic effect.

Special patient groups

The efficacy and safety of Listata in patients with impaired liver and / or kidney function, as well as in elderly patients and children under 12 years of age have not been studied.

1 film-coated tablet contains:

Tablet core composition :

Active substance: orlistat - 120.0 mg;

Excipients: sodium lauryl sulfate - 12.0 mg; acacia gum - 210.0 mg; mannitol - 580.0 mg; copovidone - 20.0 mg; crospovidone - 50.0 mg; magnesium stearate - 8.0 mg.

Tablet shell composition :

Opadrai II blue (85F205040) - 34.0 mg (polyvinyl alcohol - 40.0%, titanium dioxide - 22.48%, macrogol 3350 - 20.20%, talc - 14.80%, aluminum blue varnish - 2.28 %, iron dye yellow oxide - 0.24%).

Opadry silver (63F97546) - 6.0 mg (polyvinyl alcohol - 47.03%, talc - 27.00%, macrogol 3350 - 13.27%, pearlescent pigment - 10.00%, polysorbate-80 - 2.70% ).

hypersensitivity to orlistat or any other components of the drug;

chronic malabsorption syndrome;

pregnancy;

breastfeeding period;

children under 12 years old.

Trade name of the drug

Listata

International non-proprietary name

Orlistat

Dosage form

film-coated tablets

Composition

1 film-coated tablet contains:

Tablet core composition :

Active substance: orlistat - 120.0 mg;

Excipients: sodium lauryl sulfate - 12.0 mg; acacia gum - 210.0 mg; mannitol - 580.0 mg; copovidone - 20.0 mg; crospovidone - 50.0 mg; magnesium stearate - 8.0 mg.

Tablet shell composition :

Opadrai II blue (85F205040) - 34.0 mg (polyvinyl alcohol - 40.0%, titanium dioxide - 22.48%, macrogol 3350 - 20.20%, talc - 14.80%, aluminum blue varnish - 2.28 %, iron dye yellow oxide - 0.24%).

Opadry silver (63F97546) - 6.0 mg (polyvinyl alcohol - 47.03%, talc - 27.00%, macrogol 3350 - 13.27%, pearlescent pigment - 10.00%, polysorbate-80 - 2.70% ).

Description

Tablets are oval, biconvex in shape, film-coated blue with a pearlescent effect, with a line on one side and the symbol f on the other. On the cross section - the core is white or almost white.

Pharmacotherapeutic group

Gastrointestinal lipase inhibitor

ATX code

A08AB01

Pharmacodynamics:

Orlistat is a potent, long-acting, specific and reversible inhibitor of gastrointestinal lipases. Its therapeutic effect is carried out in the lumen of the stomach and small intestine and consists in the formation of a covalent bond with the active serine site of gastric and pancreatic lipases.

At the same time, the inactivated enzyme loses the ability to break down food fats in the form of triglycerides into absorbed free fatty acids and monoglycerides. Since the undigested triglycerides are not absorbed, the resulting decrease in caloric intake in the body leads to a decrease in body weight. Thus, the therapeutic effect of the drug is carried out without absorption into the systemic circulation.

Judging by the results of the fat content in the feces, the effect of orlistat begins 24-48 hours after ingestion. After the abolition of orlistat, the fat content in the feces after 48-72 hours usually returns to the level that took place before the start of therapy.

Clinical efficacy

In patients taking orlistat, there is a greater loss of body weight compared to patients on diet therapy. Weight loss begins within the first 2 weeks after the start of treatment and lasts from 6 to 12 months, even in patients with a negative response to diet therapy. For 2 years, there has been a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, there was a significant decrease in body fat compared to taking a placebo. Orlistat is effective in preventing re-weight gain. Re-gaining of body weight no more than 25% of the lost one is observed in about half of the patients, and in half of these patients re-gaining of body weight is not observed or even its further decrease is observed.

Patients with overweight or obesity and type 2 diabetes who take orlistat for 6 months to 1 year have a greater loss of body weight compared to patients receiving diet therapy alone. Weight loss occurs mainly due to a decrease in the amount of body fat. With orlistat therapy, a statistically and clinically significant improvement in glycemic control is observed. In addition, against the background of therapy with orlistat, there is a decrease in the dose of hypoglycemic agents in the concentration of insulin, as well as a decrease in insulin resistance.

When using orlistat for 4 years, the risk of developing type 2 diabetes is significantly reduced (by about 37% compared with placebo). The degree of risk reduction is even greater in patients with underlying impaired glucose tolerance (approximately 45%).

Maintaining body weight at a new level is observed throughout the entire period of drug use.

When using orlistat for 1 year in adolescents with obesity, there is a decrease in body mass index, a decrease in fat mass, as well as waist and hip circumference, compared with the placebo group. Also, patients treated with orlistat showed a significant decrease in diastolic blood pressure compared with the placebo group.

Pharmacokinetics:

Suction. In volunteers with normal body weight and obesity, the systemic exposure to orlistat is minimal. After a single oral dose of 360 mg, unchanged orlistat in blood plasma is not determined, which means that its concentrations are below the limit of quantitative determination (less than 5 ng / ml).

In general, after taking therapeutic doses, it was possible to detect unchanged orlistat in blood plasma only in rare cases, while its concentrations were extremely low (less than 10 ng / ml or 002 ?mol). There are no signs of cumulation, which confirms that the absorption of orlistat is minimal.

Distribution. The volume of distribution cannot be determined because orlistat is very poorly absorbed. In vitro, more than 99% of orlistat binds to blood plasma proteins (mainly lipoproteins and albumin). In minimal amounts, orlistat can penetrate into erythrocytes.

Metabolism. Orlistat is metabolized mainly in the intestinal wall. In obese patients, approximately 42% of the minimal fraction of orlistat that undergoes systemic absorption is accounted for by two main metabolites - M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with a cleaved N-formylleucine residue).

Molecules M1 and M3 have an open b-lactone ring and inhibit lipase extremely weakly (1000 and 2500 times weaker than orlistat, respectively).

Given such a low inhibitory activity and low plasma concentrations (on average 26 ng / ml and 108 ng / ml, respectively), after taking therapeutic doses, these metabolites are considered pharmacologically inactive.

Excretion. In persons with normal and overweight, the main route of elimination is the elimination of not absorbed orlistat through the intestines. About 97% of the dose taken is excreted through the intestines, with 83% in the form of unchanged orlistat.

The cumulative renal excretion of all substances structurally related to orlistat is less than 2% of the dose taken. The time to complete elimination of orlistat from the body (through the intestines and kidneys) is 3-5 days. The ratio of the routes of elimination of orlistat in volunteers with normal and overweight was the same. Both orlistat and metabolites M1 and M3 can be excreted in the bile.

Pharmacokinetics in special clinical groups

Plasma concentrations of orlistat and its metabolites (M1 and M3) in children do not differ from those in adults when comparing the same doses of orlistat. The daily excretion of fat with feces is 27% of the intake with food during orlistat therapy.

Indications:

Long-term therapy of obese patients with a body mass index (BMI) of at least 30 kg / m2 or overweight patients with a BMI of at least 28 kg / m2, including those with risk factors associated with obesity in combination with a moderately hypocaloric diet.

In combination with hypoglycemic drugs (metformin sulfonylurea derivatives and / or insulin) and / or a moderately hypocaloric diet in patients with type 2 diabetes mellitus with overweight or obesity.

Contraindications:

Hypersensitivity to orlistat or any other components of the drug; chronic malabsorption syndrome; cholestasis; pregnancy during breastfeeding; children under 12 years of age.

Pregnancy and lactation:

In studies of reproductive toxicity in animals, the teratogenic and embryotoxic effect of orlistat was not observed. In the absence of a teratogenic effect in animals, a similar effect is not expected in humans. Since there are no clinical data on the use of orlistat during pregnancy, the use of Listat in pregnant women is contraindicated.

Due to the fact that there are no data on the release of orlistat in breast milk, the use of Listat during breastfeeding is contraindicated.

Method of administration and dosage:

Inside with water.

Treatment of obese patients with a BMI of at least 30 kg / m2 or overweight patients with a BMI of at least 28 kg / m2, including those with risk factors associated with obesity in combination with a moderately low-calorie diet

Adults and children over 12 years old

The recommended dose of Listata is 1 tablet (120 mg) with each main meal (with meals or no later than 1 hour after meals).

In combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and / or insulin) and / or a moderately hypocaloric diet in patients with type 2 diabetes mellitus who are overweight or obese

Adults

The recommended dose of Listata is 1 tablet (120 mg) with each main meal (with meals or no later than 1 hour after meals).

If a meal is skipped or if the food does not contain fat, then Listat can also be skipped.

Listat should be taken in combination with a balanced, moderately hypocaloric diet containing no more than 30% calories in the form of fats. The daily intake of fat, carbohydrates and proteins must be distributed between 3 main meals.

An increase in the dose of Listata over the recommended dose (120 mg 3 times a day) does not lead to an increase in its therapeutic effect.

The efficacy and safety of Listata in patients with impaired liver and / or kidney function, as well as in elderly patients and children under 12 years of age have not been studied.

Side effects:

Clinical trial data

Side effects of the drug are systematized in relation to each of the organ systems, depending on the frequency of occurrence, using the following classification: very often (more than 1/10); often (more than 1/100 less than 1/10); infrequently (more than 1/1000 less than 1/100); rarely (more than 1/10000 less than 1/1000); very rarely including single messages (less than 1/10000).

Adverse reactions when using orlistat arose mainly from the gastrointestinal tract (GIT) and were due to the pharmacological effect of orlistat, which prevents the absorption of food fats. Very often, such phenomena as oily discharge from the rectum, gas discharge with some discharge, urge to defecate, steatorrhea, increased frequency of defecation, loose stools, flatulence, pain or discomfort in the abdomen, were noted. Their frequency increases with increasing fat content in food. Patients should be informed about the possibility of adverse reactions from the gastrointestinal tract and taught how to eliminate them by following the diet, especially in relation to the amount of fat contained in it.Eating a low-fat diet reduces the likelihood of gastrointestinal side effects and thus helps patients control and regulate their fat intake.

As a rule, these side reactions are mild and transient. They occur in the early stages of treatment (in the first 3 months), and most patients had no more than one episode of such reactions.

When treating with orlistat, the following adverse events from the gastrointestinal tract often occur: 'soft' stools pain or discomfort in the rectum fecal incontinence bloating of the abdomen tooth damage gum disease.

Were also noted very often: headache upper respiratory tract infection; influenza; often: lower respiratory tract infections urinary tract infections dysmenorrhea anxiety weakness.

In patients with type 2 diabetes mellitus, the nature and frequency of adverse events were comparable to those in persons without diabetes mellitus, overweight and obese.

The only new side effects in patients with type 2 diabetes mellitus were hypoglycemic conditions with a frequency of more than 2% and an incidence of at least 1% compared with placebo (which could result from improved compensation for carbohydrate metabolism) and often bloating.

In a 4-year clinical study, the overall safety profile did not differ from that obtained in 1- and 2-year studies. At the same time, the overall incidence of adverse events from the gastrointestinal tract decreased annually over the 4-year period of taking the drug.

Post-marketing surveillance

Rare cases of allergic reactions are described, the main clinical manifestations of which were skin rash itching urticaria angioedema bronchospasm and anaphylaxis.

Described are very rare cases of bullous rash of increased activity of transaminases and alkaline phosphatase, as well as some possibly serious cases of hepatitis (a causal relationship with taking orlistat or pathophysiological mechanisms of development have not been established).

With the simultaneous use of orlistat with indirect anticoagulants, cases of a decrease in prothrombin, an increase in the values ??of the international normalized ratio (INR) and unbalanced anticoagulant therapy, which led to a change in hemostatic parameters, were recorded.

Cases of rectal bleeding, diverticulitis, pancreatitis, cholelithiasis and oxalate nephropathy have been reported (incidence not known).

With the simultaneous administration of orlistat and antiepileptic drugs, cases of seizures have been observed (see the section 'Interaction with other drugs').

Overdose:

In persons with normal body weight and obese patients, taking single doses of 800 mg or multiple administration of orlistat 400 mg 3 times a day for 15 days was not accompanied by the appearance of significant adverse events. In addition, obese patients have experience of using orlistat 240 mg 3 times a day for 6 months, which was not accompanied by a significant increase in the frequency of adverse events.

In cases of overdose of orlistat, either the absence of adverse events was reported or the adverse events did not differ from those observed when taking orlistat in therapeutic doses.

In case of severe overdose of orlistat, it is recommended to observe the patient for 24 hours. According to studies in humans and animals, any systemic effects that could be associated with the lipase-inhibiting properties of orlistat should be quickly reversible.

Interaction:

No interaction of orlistat with amitriptyline atorvastatin biguanides digoxin fibrates fluoxetine losartan phenytoin oral contraceptives phentermine pravastatin warfarin nifedipine GITS (gastrointestinal therapeutic system) and nifedipine with slow release between drugs However, it is necessary to monitor INR values ??while concomitant therapy with warfarin or other indirect anticoagulants.

ѕри одновременном приеме с орлистатом отмечалось уменьшение всасывани¤ витаминов D ? и бета-каротина. ?сли рекомендованы поливитамины их следует принимать не менее чем через 2 ч после приема орлистата или перед сном.

ѕри одновременном приеме орлистата и циклоспорина отмечалось снижение концентрации циклоспорина в плазме крови поэтому рекомендуетс¤ более частое определение концентрации циклоспорина в плазме крови при одновременном приеме циклоспорина и орлистата.

ѕри приеме внутрь амиодарона во врем¤ терапии орлистатом отмечалось снижение системной экспозиции амиодарона и дезэтиламиодарона (на 25- 30%) однако в св¤зи со сложной фармакокинетикой амиодарона клиническа¤ значимость этого ¤влени¤ не ¤сна. ?обавление орлистата к длительной терапии амиодароном возможно приведет к снижению терапевтического эффекта амиодарона (исследований не проводилось).

—ледует избегать одновременного приема орлистата и акарбозы из-за отсутстви¤ данных фармакокинетических исследований.

ѕри одновременном приеме орлистата и противоэпилептических препаратов наблюдались случаи развити¤ судорог. ѕричинно-следственна¤ св¤зь между развитием судорог и терапией орлистатом не установлена. “ем не менее следует мониторировать состо¤ние пациентов на предмет возможных изменений частоты и/или т¤жести судорожного синдрома.

ќсобые указани¤:

ѕрепарат Ћистата эффективен в плане длительного контрол¤ массы тела (снижение массы тела и ее поддержание предотвращение повторной прибавки массы тела). Ћечение препаратом Ћистата приводит к улучшению профил¤ факторов риска и заболеваний сопутствующих ожирению включа¤ гиперхолестеринемию сахарный диабет 2 типа нарушение толерантности к глюкозе гиперинсулинемию артериальную гипертензию и к уменьшению количества висцерального жира.

ѕри применении в комбинации с такими гипогликемическими препаратами как метформин производные сульфонилмочевины и/или инсулин у пациентов с сахарным диабетом 2 типа с избыточной массой тела (»ћ“ не менее 28 кг/м2 ) или ожирением (»ћ“ не менее 30 кг/м2) препарат Ћистата в сочетании с умеренно гипокалорийной диетой способствует дополнительному улучшению компенсации углеводного обмена.

¬ клинических исследовани¤х у большинства пациентов концентрации витаминов A D ?   и бета-каротина в ходе четырех лет терапии орлистатом оставались в пределах нормы. ?л¤ обеспечени¤ адекватного поступлени¤ всех минеральных веществ можно примен¤ть поливитамины.

ѕациент должен получать сбалансированную умеренно гипокалорийную диету содержащую не более 30% калоража в виде жиров. –екомендуетс¤ питание богатое фруктами и овощами. —уточное потребление жиров углеводов и белков необходимо распредел¤ть на три основных приема. ¬еро¤тность побочных реакций со стороны ? “ может увеличиватьс¤ если препарат Ћистата принимают на фоне питани¤ богатого жирами (например 2000 ккал/сут из них более 30% в виде жиров что равн¤етс¤ примерно 67 г жира). ?сли препарат Ћистата принимают с пищей очень богатой жиром веро¤тность желудочно-кишечных реакций увеличиваетс¤.

” пациентов с сахарным диабетом 2 типа уменьшение массы тела при лечении препаратом Ћистата сопровождаетс¤ улучшением компенсации углеводного обмена что может позволить или потребовать снижени¤ дозы гипогликемических препаратов (например производных сульфонилмочевины).

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

ѕрепарат Ћистата не вли¤ет на способность управл¤ть транспортными средствами и механизмами. ѕациенты с сахарным диабетом 2 типа примен¤ющие препарат Ћистата в комбинации с гипогликемическими препаратами должны соблюдать осторожность при управлении транспортными средствами и механизмами в св¤зи с возможным развитием гипогликемии сопровождающейс¤ головокружением нарушением зрени¤.

‘орма выпуска/дозировка:

“аблетки покрытые пленочной оболочкой 120 мг.

”паковка:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and printed aluminum foil varnished.

1 2 3 6 or 9 blisters, together with instructions for medical use, are placed in a box made of cardboard.

Storage conditions:

In a dark place at a temperature not exceeding 25 ? C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Vacation conditions

On prescription