Listat - instructions for use, doses, side effects, contraindications

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.

Composition of the tablet shell:

Fall Light II blue (85F205040) - 34,0 mg (polyvinyl alcohol 40.0%, titanium dioxide 22.48%, macrogol 3350-20.20%, talc 14.80%, lacquer aluminum blue - 2.28%, iron oxide coloring yellow - 0.24%).

Fall 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:

The tablets are oval, biconvex, covered with a film shell of blue color with pearlescent effect, with a risk on one side and a symbol "f" - with another. On the cross section - the core is white or almost white.

Pharmacotherapeutic group:Lipase GIT inhibitor

ATX: & nbsp

A.08.A.B.01 Orlistat

Pharmacodynamics:

Orlistat - a powerful, specific and reversible inhibitor of gastrointestinal lipases, which has a long-lasting effect. 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 portion of the gastric and pancreatic lipases.

The inactivated enzyme loses its ability to break down the food fats that come in the form of triglycerides, to sucking free fatty acids and monoglycerides.Since uncleaved triglycerides are not absorbed, the resulting decrease in the intake of calories into the body leads to a decrease in body weight. Thus, the therapeutic effect of the drug is carried out without absorption into the systemic bloodstream.

Judging by the results of fat content in feces, the action of orlistat begins 24-48 hours after ingestion. After cancellation of orlistat, the fat content in the stool after 48-72 hours usually returns to the level that occurred before the start of therapy.

Clinical efficacy

In patients receiving orlistat, there is a large loss of body weight compared with patients on diet therapy. The decrease in body weight begins already within the first 2 weeks after the beginning of treatment and lasts from 6 to 12 months even in patients with a negative response to diet therapy. For 2 years, a statistically significant improvement in the profile of metabolic risk factors associated with obesity has been observed. In addition, compared to taking placebo, there is a significant decrease in the amount of fat in the body. Orlistat It is effective in preventing repeated weight gain.A re-set of body weight, not more than 25% of the lost weight, is observed in about half of the patients, and half of these patients do not recur, or even notice a further decrease in body weight.

In patients with overweight or obesity and type 2 diabetes mellitus, orlistat for 6 months to 1 year, there is a large loss of body weight in comparison with patients receiving only diet therapy. The loss of body weight occurs mainly due to a decrease in the amount of fat in the body. When conducting orlistat therapy, a statistically and clinically significant improvement in glycemic control is observed. In addition, against the background of orlistat therapy, there is a decrease in the dose of hypoglycemic agents, insulin concentrations, and a decrease in insulin resistance.

When orlistat is used for 4 years, the risk of developing type 2 diabetes mellitus is reduced significantly (by about 37% compared with placebo). The degree of risk reduction is even more significant in patients with initial impairment of glucose tolerance (approximately 45%).

Maintenance of body weight at a new level is observed during the entire period of application of the drug.

In the application of orlistat for 1 year in adolescents with obesity, there is a decrease in body mass index, a reduction in fat mass, and waist and hip circumference as compared with the placebo group. Also, patients who received orlistat therapy had a significant reduction in diastolic blood pressure compared to the placebo group.

Pharmacokinetics:

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

In general, after taking therapeutic doses, identify unchanged orlistat in blood plasma was possible only in rare cases, while its concentrations were extremely small (less than 10 ng / ml or 0.02 μmol). Signs of cumulation are absent, which confirms that the absorption of orlistat is minimal.

Distribution. The volume of distribution can not be determined, because orlistat very poorly absorbed. In vitro orlistat more than 99% associated with blood plasma proteins (mainly with lipoproteins and albumin). In minimum quantities orlistat can penetrate into erythrocytes.

Metabolism. Metabolism of orlistat occurs mainly in the wall of the intestine. In obese patients, approximately 42% of the minimum fraction of orlistat that undergoes systemic absorption is accounted for by two major metabolites - M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with a split residue N-formleleucine).

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

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

Excretion. In individuals with normal and excessive body weight, the main way of excretion is the removal of not absorbed orlistat through the intestine. About 97% of the dose is taken out through the intestine, 83% in the form of unchanged orlistat.

The total renal excretion of all substances structurally associated with orlistat is less than 2% of the dose taken. Time until the complete excretion of orlistat from the body (through the intestine and kidneys) is 3-5 days.The ratio of pathways for orlistat in volunteers with normal and overweight was the same. how orlistat, and metabolites M1 and M3, can be excreted with bile.

Pharmacokinetics in special clinical groups

Concentrations of orlistat and its metabolites (M1 and M3) in the blood plasma in children do not differ from those in adults when comparing identical doses of orlistat. Daily excretion of fat with feces is 27% of intake from food with orlistat therapy.

Indications:

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

In combination with hypoglycemic drugs (metformin, sulfonylureas and / or insulin derivatives) 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; syndrome of chronic malabsorption; cholestasis; pregnancy, the period of breastfeeding; children under 12 years.

Pregnancy and lactation:

In studies of reproductive toxicity in animals, teratogenic and embryotoxic effects of orlistat were not observed. In the absence of a teratogenic effect in animals, a similar effect in humans is not expected. 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 is no data on the isolation of orlistat with breast milk, the use of Listat during breastfeeding is contraindicated.

Dosing and Administration:

Inside, washing down with water.

Treatment of obese patients with a BMI of at least 30 kg / m² or patients with excessive body weight with a BMI of at least 28 kg / m², including those associated with obesity risk factors, combined with a moderately low-calorie diet

Adults and children over 12 years of age

The recommended dose of Lystat is 1 tablet (120 mg) with each main meal (during meals or not later than 1 hour after meals).

Adults

The recommended dose of Lystat is 1 tablet (120 mg) with each main meal (during meals or not later than 1 hour after meals).

If food intake is missed or if the food does not contain fat, then the Listat preparation can also be skipped.

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

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

Efficacy and safety of Listat in patients with impaired liver and / or kidney function, and in elderly patients and children under 12 years not investigated.

Side effects:

Clinical Trials Data

Side effects of the drug are systematized relative 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 with orlistat appeared mainly from the gastrointestinal tract (GIT) and were due to the pharmacological action of orlistat, which prevents the absorption of food fats. Very often, such phenomena as oily discharge from the rectum, the release of gases with a certain amount of discharge, imperative urges for defecation, steatorrhoea, frequent bowel movements, loose stools, flatulence, pain or discomfort in the abdomen were very often noted. Their frequency increases with increasing fat content in food. Patients should be informed of the potential for side effects from the gastrointestinal tract and how to eliminate them by diet, especially regarding the amount of fat contained in it. The use of a low-fat diet reduces the likelihood of side effects on the part of the gastrointestinal tract and thereby helps patients to monitor and regulate the consumption of fats.

As a rule, these adverse reactions are mild and transient. They occur in the early stages of treatment (in the first 3 months), and in most patients there was not more than one episode of such reactions.

When treating orlistatom often the following undesirable phenomena from the gastrointestinal tract: "soft" stool, pain or discomfort in the rectum, fecal incontinence, bloating, dental damage, gum lesion.

They were also noted very often: headache, upper respiratory tract infections, influenza; often: lower respiratory tract infections, urinary tract infections, dysmenorrhea, anxiety, weakness.

In patients with type 2 diabetes mellitus, the nature and incidence of adverse events were comparable to those in people without diabetes mellitus with excessive body weight and obesity.

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

In a 4-year clinical trial, 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 during the 4-year period of drug intake.

Postmarketing surveillance

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

Very rare cases of bullous rash, increased activity of transaminases and alkaline phosphatase, as well as separate, possibly serious, cases of hepatitis development (cause-and-effect relationship with orlistat administration or pathophysiological mechanisms of development have not been established).

With the simultaneous use of orlistat with anticoagulants of indirect effect, cases of a decrease in prothrombin, an increase in the values of the international normalized ratio (INR) and unbalanced therapy with anticoagulants have been registered, which led to a change in the haemostatic parameters.

Reported cases of rectal bleeding, diverticulitis, pancreatitis, cholelithiasis and oxalate nephropathy (incidence is not known).

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

Overdose:

In individuals with normal body weight and obese patients, taking single doses of 800 mg or repeated taking orlistat 400 mg 3 times a day for 15 days was not accompanied by the appearance of significant adverse events. In addition, patients with obesity experience the use of orlistat 240 mg 3 times a day for 6 months, which was not accompanied by a significant increase in the incidence of adverse events.

In cases of an overdose of orlistat, either the absence of undesired events was reported, or the undesirable events did not differ from those observed with the administration of orlistat at therapeutic doses.

In case of severe overdose of orlistat it is recommended to observe the patient within 24 hours. According to studies in humans and animals, any systemic effects that could be associated with lipase inhibitory 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, sibutramine or ethanol (based on studies of interactions between drugs). However, it is necessary to monitor the indices of INR with simultaneous therapy with warfarin or other anticoagulants of indirect action.

At a simultaneous intake with orlistatom there was a decrease in the absorption of vitamins D, E and beta-carotene. If recommended multivitamins, they should be taken no less than 2 hours after taking orlistat or before bedtime.

With the simultaneous administration of orlistat and cyclosporine, a decrease in the concentration of cyclosporine in the blood plasma was noted, therefore, a more frequent determination of the concentration of cyclosporine in the blood plasma is recommended while simultaneous administration of cyclosporine and orlistat.

When administered amiodarone during therapy with orlistatom, the systemic exposure of amiodarone and desethylamiodarone decreased by 25-30%, but due to the complicated pharmacokinetics of amiodarone, the clinical significance of this phenomenon is not clear. Adding orlistat to prolonged therapy with amiodarone may lead to a decrease in the therapeutic effect of amiodarone (no studies have been performed).

It is necessary to avoid the simultaneous administration of orlistat and acarbose due to the lack of pharmacokinetic data.

With the simultaneous administration of orlistat and antiepileptic drugs, cases of seizures developed. Causal relationship between the development of seizures and orlistat therapy is not established. Nevertheless, patients should be monitored for possible changes in the frequency and / or severity of the seizure syndrome.

Special instructions:

The drug Listat is effective in terms of long-term control of body weight (weight loss and maintenance, prevention of repeated weight gain). Treatment with Listat leads to an improvement in the profile of risk factors and diseases associated with obesity, including hypercholesterolemia, type 2 diabetes, impaired glucose tolerance, hyperinsulinemia, arterial hypertension, and a reduction in visceral fat.

When used in combination with such hypoglycemic drugs as metformin, sulfonylureas and / or insulin derivatives in patients with type 2 diabetes mellitus with an overweight (BMI no less than 28 kg / m² ) or obesity (BMI no less than 30 kg / m²), the drug Listat in combination with a moderately hypocaloric diet contributes to an additional improvement in the compensation of carbohydrate metabolism.

In clinical studies, in most patients, concentrations of vitamins A, D, E, K and beta-carotene during the four years of orlistat therapy remained within the normal range. To ensure adequate intake of all minerals, multivitamins.

The patient should receive a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fats. We recommend eating rich in fruits and vegetables. The daily intake of fats, carbohydrates and proteins must be divided into three main methods. The likelihood of adverse reactions from the GI tract can increase if the Lystat preparation is taken against a diet rich in fats (for example, 2000 kcal / day, of which more than 30% is fat, which is about 67 g of fat). If the drug Listita is taken with food very rich in fat, the likelihood of gastrointestinal reactions increases.

In patients with type 2 diabetes mellitus, a decrease in body weight when treated with Listat is accompanied by an improvement in the compensation of carbohydrate metabolism,which may allow or require a reduction in the dose of hypoglycemic drugs (eg, sulfonylurea derivatives).

Effect on the ability to drive transp. cf. and fur:

The drug Listat does not affect the ability to drive vehicles and mechanisms. Patients with type 2 diabetes who use Listat in combination with hypoglycemic drugs should be careful in managing vehicles and mechanisms in connection with the possible development of hypoglycemia, accompanied by dizziness, visual impairment.

Form release / dosage:Tablets, film-coated, 120 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 6 or 9 contour mesh packages together with instructions for medical use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002174

Date of registration:06.08.2013 / 11.02.2015

Expiration Date:06.08.2018

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia

Information update date: & nbsp11.04.2018

Illustrated instructions

Instructions

Listat (Listata)