Listata, 120 mg 20 pcs.

Pharmacodynamics

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

Inactivated enzyme thereby loses the ability to break down food fats coming in the form of triglycerides, into absorbed 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. Thus, the therapeutic action of the drug is carried out without absorption into the systemic blood flow.

Judging by the results of fecal fat content the action of orlistat starts 24-48 hours after intake. After discontinuation of orlistat, fecal fat content in 48-72 h usually returns to pre-therapy levels.

Clinical efficacy

Patients taking orlistat show 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. Over 2 years, there is a statistically significant improvement in the profile of metabolic risk factors associated with obesity. 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 body weight, not more than 25% of the lost weight, is observed in about half of the patients, and in half of these patients re-gain of body weight is not observed or even further weight loss is noted.

In patients with overweight or obesity and type 2 diabetes, taking orlistat for 6 months to 1 year, there is greater weight loss compared to 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 treatment with orlistat there is a decrease in the dose of hypoglycemic agents, insulin concentration, 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 to placebo). The degree of risk reduction is even more significant in patients with initial impaired glucose tolerance (approximately by 45%).

Maintenance of body weight at the new level is observed during the whole period of the drug use.

When orlistat was used for 1 year in adolescents with obesity, a decrease in BMI, fat mass, as well as waist and hip circumference was observed compared to the placebo group. Also, patients treated with orlistat showed a significant decrease in diastolic BP compared to the placebo group.

Pharmacokinetics
Absorption

In volunteers with normal body weight and obesity, the 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, after therapeutic doses unchanged orlistat was detected in plasma only in rare cases, and its concentrations were extremely low (less than 10 ng/ml or 0.02 μmol). There are no signs of cumulation, which confirms that absorption of orlistat is minimal.

Distribution

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

Metabolism

Metabolism of orlistat is carried out 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 major metabolites, M1 (a four-member hydrolyzed lactone ring) and M3 (M1 with a detached N-formylleucine residue).

M1 and M3 molecules have an open b-lactone ring and inhibit very weakly lipase (1000 and 2500 times weaker than orlistat, correspondingly).

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

Excretion

In persons with normal and excess body weight, the major route of excretion is the excretion of unabsorbed orlistat through the intestine. About 97% of the administered dose is excreted through the intestine, with 83% 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 its metabolites M1 and M3 can be excreted with 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. Daily excretion of fat with feces is 27% of intake with food during orlistat therapy.

Indications

Obesity, Wrong Diet, Overeating – long-term therapy in obese patients with BMI at least 30 kg/m2 or in overweight patients with BMI at least 28 kg/m2, including Having obesity-associated risk factors, in combination with moderately hypocaloric diet;

– in combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and/or insulin) and/or moderately hypocaloric diet in patients with type 2 diabetes with excessive body weight or obesity.

Active ingredient

Orlistat

How to take, the dosage

Oral with water.

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

Adults and children over 12 years

Recommended dose of the preparation Listat – 1 tablet (120 mg) with each main meal (during food or not later than 1 hour after a meal).

In combination with hypoglycemic agents (metformin, sulfonylurea derivatives and/or insulin) and/or moderately hypocaloric diet in patients with diabetes mellitus type 2 with excessive body weight or obesity

Adults

The recommended dose of the drug Listat 1 tablet. (120 mg) with each main meal (during the meal or not later than 1 hour after the meal).

If the meal is skipped or if the food contains no fat, the drug Listat 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 fat. The daily intake of fats, carbohydrates and proteins should be distributed between the three main meals.

The increase in the dose of the preparation Listata over the recommended one (120 mg 3 times per day) does not lead to the increase of its therapeutic effect.

Efficacy and safety of Listat in patients with hepatic and/or renal dysfunction as well as in elderly patients and children under 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 was found, nifedipine GITS (gastrointestinal therapeutic system) and slow-release nifedipine, sibutramine, or ethanol (based on studies of drug-drug interactions). However it is necessary to monitor INR value in concurrent therapy with warfarin or other anticoagulants of indirect action.

A decrease of absorption of vitamins D, E and beta-carotene was noted while concurrent use with orlistat. If multivitamins are recommended, they should be taken at least 2 hours after taking orlistat or before sleep.

In concomitant use of orlistat and cyclosporine a decrease of cyclosporine plasma concentration was noted, therefore it is recommended to determine cyclosporine plasma concentration more frequently in concomitant use of cyclosporine and orlistat.

A decrease in systemic exposure to amiodarone and desethylamiodarone (by 25-30%) has been observed with oral amiodarone administration during therapy with orlistat, but due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is unclear. Adding orlistat to long-term therapy with amiodarone may result in a reduction of the therapeutic effect of amiodarone (no studies have been conducted).

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

Convulsions have been observed when taking orlistat and antiepileptic drugs simultaneously. The causal relationship between the development of seizures and orlistat therapy has not been established. Nevertheless, patients should be monitored for possible changes in the frequency and/or severity of seizures.

Special Instructions

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

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

The concentrations of vitamins A, D, E, K and beta-carotene during 4 years of therapy with Orlistat remained within the normal range. 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 divided into three main meals. The possibility of gastrointestinal side effects may increase if the drug Listata is taken against a diet rich in fats (for example, 2000 kcal/day, of which more than 30% is fat, which equals about 67 g of fat). If the drug Listat is taken with a diet very rich in fat, the likelihood of gastrointestinal reactions increases.

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

Influence on the ability to drive vehicles and mechanisms

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

Contraindications

– Hypersensitivity to orlistat or any other drug components;
– Chronic malabsorption syndrome;
– Cholestasis;
– Pregnancy, breastfeeding;
– Childhood under 12 years.

Side effects

Data from clinical trials