Listata, 120 mg 90 pcs

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

The inactivated enzyme loses its ability to break down food fats that come in the form of triglycerides into absorbable free fatty acids and monoglycerides. Since unchecked triglycerides are not absorbed, the resulting decrease in the intake of calories into the body leads to a decrease in body weight. This way the therapeutic action of the drug is carried out without absorption into the systemic blood flow.

Based on the results of fecal fat content, the action of orlistat starts 24-48 hours after taking it. After discontinuation of orlistat, fecal fat content in 48-72 h usually returns to pre-therapy levels.

Clinical effectiveness

Patients taking orlistat have greater weight loss compared to patients on diet therapy. Weight loss begins within the first 2 weeks of starting treatment and continues for 6 to 12 months, even in patients with a negative response to diet therapy.

A statistically significant improvement in the profile of metabolic risk factors associated with obesity is observed over 2 years. In addition, there is a significant decrease in body fat compared to placebo administration. Orlistat is effective in preventing weight gain again. Re-gain of weight, not more than 25% of the lost weight, is observed in about half of patients, and in the other half of patients re-gain of weight is not observed, or even a further decrease in weight is noted.

The patients with overweight or obesity and type 2 diabetes mellitus taking orlistat for 6-12 months have greater weight loss than patients receiving diet therapy alone. The weight loss is mainly due to a decrease in body fat. During 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 concentration, and a decrease in insulin resistance.

The use of orlistat for 4 years significantly reduces the risk of developing type 2 diabetes (by about 37% compared to placebo). The degree of risk reduction is even greater in patients with baseline impaired glucose tolerance (approximately 45%).

The maintenance of body weight at new levels is observed throughout the duration of drug use.

The use of orlistat for 1 year in obese adolescents showed decreases in body mass index (BMI), fat mass, and waist and hip circumference compared to the placebo group. Also, patients treated with orlistat had a significant decrease in dAP compared to the placebo group.

Pharmacokinetics

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

In general, unchanged orlistat has only rarely been detected in plasma after therapeutic doses, with very low concentrations (less than 10 ng/ml or 0.02 µmol). There were no signs of cumulation, confirming that absorption of orlistat was minimal.

Distribution. V_d cannot be determined because orlistat is very poorly absorbed. In vivo orlistat is more than 99% bound to plasma proteins (mainly lipoproteins and albumin). In minimal amounts orlistat can penetrate into erythrocytes.

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

The M1 and M3 molecules have an open β-lactone ring and are extremely weak inhibitors of lipase (weaker than orlistat by 1000 and 2500 times, respectively). Given this low inhibitory activity and low plasma concentrations (average 26 and 108 ng/ml, respectively) after therapeutic doses, these metabolites are considered pharmacologically inactive.

Elimination. In persons of normal and excess body weight, the major route of excretion is excretion of unabsorbed orlistat through the intestine. About 97% of the administered dose is excreted through the intestine, and 83% of it is excreted as unchanged orlistat. The total renal excretion of all substances structurally related to orlistat is less than 2% of the administered dose. The time to complete excretion of orlistat from the body (through the intestine and the kidneys) is 3-5 days. The ratio of orlistat excretion routes in normal and overweight volunteers was similar. Both orlistat and M1 and M3 metabolites can be excreted with bile.

Particular patient groups

Children. 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. Daily excretion of fat with feces is 27% of the intake with food during orlistat therapy.

Indications

Active ingredient

Composition

Active ingredient:

orlistat 120 mg;

Associates:

sodium lauryl sulfate, 12 mg;

acacia gum, 210 mg;

ludiflash (mannitol – 84-92%, crosspovidone – 4-6%, polyvinyl acetate – 3.5-6%, povidone – 0.25-0.6%) – 580 mg;

Copovidone – 20 mg;

Crospovidone – 50 mg;

Magnesium stearate – 8 mg;

Film coating:

Opadray II blue (85F205040) (polyvinyl alcohol – 40%, titanium dioxide – 22.48%, macrogol 3350 – 20.2%, talc – 14.8%, aluminum blue varnish – 2.28%, iron oxide yellow dye – 0.24%) – 34 mg;

Silver Opadray (63F97546) (polyvinyl alcohol – 47.03%, talc – 27%, macrogol 3350 – 13.27%, pearlescent pigment – 10%, polysorbate 80 – 2.7%) – 6 mg.

How to take, the dosage

Ingestion with water.

The 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 patients with obesity-related risk factors in combination with a moderately nutrient-poor diet: 1 tablet (120 mg) with each main meal (with a meal or at least 1 hour after a meal) is recommended for adults and children older than 12 years.

In combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and/or insulin) and/or a moderately hypocaloric diet in patients with type 2 diabetes with excessive body weight or obesity: Adults – recommended dose of Listat is 1 tablet (120 mg) with each main meal (at meal or within 1 hour after meal).

If a meal is skipped or the food does not contain fat, Lystat may also be skipped.

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

Extending the dose of Listat above the recommended dose (120 mg 3 times daily) does not increase its therapeutic effect.

Efficacy and safety of Listat in patients with hepatic and/or renal dysfunction as well as in elderly patients and children less than 12 years old have not been studied.

Interaction

No interaction of orlistat with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine GITS (gastrointestinal therapy system) and slow-release nifedipine, sibutramine or ethanol (based on interactions between drugs) was found. However, it is necessary to monitor MHO values when concomitant therapy with warfarin or other indirect anticoagulants.

When concomitant use with orlistat it was observed a decrease in absorption of vitamins D, E and beta-carotene. If multivitamins are recommended, they should be taken at least 2 hours after taking orlistat or before bedtime.

A decrease in plasma concentrations of cyclosporine has been noted with concomitant administration of orlistat and cyclosporine, so more frequent determination of plasma cyclosporine concentrations is recommended with concomitant administration of cyclosporine and orlistat.

Amiodarone ingestion during therapy with orlistat has been noted to decrease systemic exposure to amiodarone and desethylamiodarone (by 25-30%), but due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is unclear. Adding orlistat to long-term therapy with amiodarone would possibly decrease the therapeutic effect of amiodarone (no studies have been conducted).

The concomitant administration of orlistat and acarbose should be avoided due to the lack of data from pharmacokinetic studies.

Concomitant administration of orlistat and antiepileptic drugs has been observed to cause seizures. A causal relationship between the development of seizures and therapy with orlistat has not been established. Nevertheless, patients should be monitored for possible changes in frequency and/or severity of seizures.

Special Instructions

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

When used in combination with hypoglycemic drugs such as metformin, sulfonylurea derivatives and/or insulin, in patients with type 2 diabetes with excess body weight (BMI at least 28 kg/m2) or obesity (BMI at least 30 kg/m2), Listat in combination with a moderately hypocaloric diet promotes additional improvement of carbohydrate metabolism compensation.

In clinical studies in most patients, concentrations of vitamins A, D, E, K and beta-carotene remained within normal limits during four years of therapy with orlistat. Multivitamins may be used to ensure adequate intake of all minerals.

The patient should receive a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fat. A diet rich in fruits and vegetables is recommended. The daily intake of fats, carbohydrates and proteins should be distributed into three main meals.

The chance of adverse gastrointestinal reactions may increase if Listat is taken against a fatty diet (e.g., 2000 kcal/day, of which more than 30% is fat, which is about 67 g fat). If Listat is taken with a very high-fat diet, the chance of gastrointestinal reactions increases.

In patients with type 2 diabetes, the reduction in body weight with treatment with Listat is accompanied by improved carbohydrate metabolism compensation, which may allow or require a reduction in the dose of hypoglycemic drugs (such as sulfonylurea derivatives).

Impact on the ability to drive vehicles and operate mechanisms.Listat does not affect the ability to operate vehicles and mechanisms. Patients with type 2 diabetes mellitus who use the drug Listata in combination with hypoglycemic agents must be careful when driving vehicles and operating machinery due to possible development of hypoglycemia accompanied with dizziness and visual disturbances.

Contraindications

Side effects

Gastrointestinal disorders: often – “soft” stool, pain or discomfort in the rectum, fecal incontinence, abdominal bloating, dental lesions, gum lesions.

Other adverse reactions: very common – headache, upper respiratory tract infections, flu; common – lower respiratory tract infections, urinary tract infections, dysmenorrhea, anxiety, weakness.

Pregnancy use

The teratogenic and embryotoxic effects of orlistat have not been observed in animal reproductive toxicity studies. In the absence of teratogenic effects in animals, a similar effect in humans is not expected.

Because there are no clinical data on the use of orlistat during pregnancy, the use of Listat in pregnant women is contraindicated.

Because there are no data on excretion of orlistat with breast milk, use of Listat during breastfeeding is contraindicated.

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