Listata, 120 mg 80 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 formation of covalent bonding with the active serine site of gastric and pancreatic lipases.

Inactivated enzyme in this case loses the ability to break down food fats coming in the form of triglycerides into absorbable free fatty acids and monoglycerides.

Since unrepaired triglycerides are not absorbed, the resulting decrease in caloric intake 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 blood flow. Judging by the results of fecal fat content, the action of orlistat begins 24-48 hours after intake. After discontinuation of orlistat the content of fat in feces in 48-72 hours usually returns to the level before the beginning of therapy.

Clinical efficacy. Patients taking orlistat show greater weight loss compared to patients on diet therapy.

The 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 reduction in body fat compared to placebo administration. Orlistat is effective in preventing weight gain again.

Re-gain of body weight, no more than 25% of that lost, is observed in about half of the patients, and half of these patients have no re-gain of body weight or even further weight loss is noted.

Overweight or obese patients with type 2 diabetes mellitus taking orlistat for 6 months to 1 year have greater weight loss compared with patients receiving diet therapy alone.

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, as well as a decrease in insulin resistance.

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

Maintenance of body weight at a new level is observed during the entire period of the drug administration. When orlistat is used for 1 year in adolescents with obesity the decrease of BMI, fat mass as well as waist and hip circumference is observed as compared to the placebo group.

Also, patients treated with orlistat showed a significant decrease in diastolic BP compared to the placebo group.

Indications

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, including having obesity-associated risk factors, 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 excess body weight or obesity.

Active ingredient

Orlistat

How to take, the dosage

Orally 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 obesity-associated risk factors, in combination with moderately low-calorie diet.

Adults and children over 12 years old.

The recommended dose of the drug Listat is 1 tablet (120 mg) with each main meal (with a meal or no 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 type 2 with excessive body weight or obesity.

Adults.

Recommended dosage of the drug Listat 1 tablet (120 mg) with each main meal (with a meal or not later than 1 hour after a meal). If the meal is skipped or if the food does not contain fat, the drug Listat can 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 three main meals.

The increase of the dosage of the drug Lystata over the recommended one (120 mg three times per day) doesn’t lead to the increase of its therapeutic effect. Efficacy and safety of the drug 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 values when concomitant therapy with warfarin or other indirect anticoagulants. When concomitant use with orlistat it was noted decrease of 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 going to bed. A decrease in plasma concentrations of cyclosporine has been observed while concomitant administration of orlistat and cyclosporine, therefore it is recommended to determine plasma concentrations of cyclosporine more frequently while concomitant administration of cyclosporine and orlistat.

A decrease in systemic exposure to amiodarone and desethylamiodarone (by 25-30%) has been observed when taking oral amiodarone 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 decrease the therapeutic effect of amiodarone (no studies have been conducted). Concomitant administration of orlistat and acarbose should be avoided due to the lack of data of pharmacokinetic studies.

Convulsions have been observed when taking orlistat concomitantly with antiepileptic drugs.

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

The drug Listata is effective in terms of long-term body weight control (weight reduction and maintenance, prevention of weight gain again).

Lystata treatment improves the profile of risk factors and diseases accompanying obesity, including hypercholesterolemia, type 2 diabetes, impaired glucose tolerance, hyperinsulinemia, arterial hypertension, and a decrease in 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.

Vitamin A, D, E, K and beta-carotene concentrations in the majority of patients 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 likelihood of adverse gastrointestinal reactions may increase if the drug Lystata is taken against a diet rich in fats (e.g., 2000 kcal/d, of which more than 30% in the form of fat, which equals about 67 g of fat).

If Listat is taken with a diet very rich in fat, the likelihood of gastrointestinal reactions increases. In patients with type 2 diabetes mellitus, 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 (e.g., sulfonylurea derivatives).

Effect on the ability to drive vehicles and mechanisms.

Listat 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 exercise caution when driving vehicles and mechanisms due to the possible development of hypoglycemia accompanied by dizziness and visual impairment.

Contraindications

Hypersensitivity to orlistat or any other drug components; chronic malabsorption syndrome; cholestasis; pregnancy, breast-feeding; children under 12 years of age.

Side effects

Data from clinical studies.

Side effects of the drug are systematized in relation to each of the organ systems according to the frequency of occurrence, using the following classification: very frequently (more than 1/10); frequently (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); rarely (more than 1/10 000, less than 1/1000); very rarely, including single reports (less than 1/10 000).

Adverse reactions when using orlistat occurred primarily on the gastrointestinal side and were due to the pharmacological action of orlistat, which interferes with the absorption of food fats.

Very often such phenomena as oily discharge from the rectum, discharge of gases with some discharge, urgent defecation urges, steatorrhea, increased frequency of defecation, liquid stools, flatulence, pain or discomfort in the abdomen were observed.

Their frequency increases with an increase in the fat content of food. Patients should be informed about the possibility of gastrointestinal adverse reactions and educated on how to manage them by following the diet, especially with regard to the amount of fat in it.

The use of a low-fat diet reduces the likelihood of gastrointestinal adverse events and thereby helps patients control and manage their fat intake.Generally, these adverse reactions are mild and transient.

They occur in the early stages of treatment (in the first 3 months), with most patients having no more than one episode of such reactions. The following gastrointestinal adverse events frequently occur during treatment with orlistat: “soft” stools, pain or discomfort in the rectum, fecal incontinence, abdominal bloating, dental lesions, gum lesions.

Headache, upper respiratory tract infections, influenza; lower respiratory tract infections, urinary tract infections, dysmenorrhea, anxiety, weakness were also noted very frequently. In patients with type 2 diabetes the nature and frequency of adverse events were comparable to those in those without diabetes mellitus with excessive body weight and obesity.

The only new adverse events in patients with type 2 diabetes were hypoglycemic conditions, occurring with a frequency of more than 2% and an incidence of at least 1% compared with placebo (which may have resulted from improved carbohydrate metabolism compensation), and frequent abdominal bloating.

In the 4-year clinical trial, the overall safety profile did not differ from that obtained in the 1- and 2-year studies. The overall incidence of GI adverse events decreased annually over the 4-year period of the drug.

Post-marketing surveillance. Rare cases of allergic reactions were described, the main clinical manifestations of which were skin rash, pruritus, urticaria, angioedema, bronchospasm and anaphylaxis.

Very rare cases of bullous rash, increased transaminase and alkaline phosphatase activity, as well as isolated, possibly serious, cases of hepatitis development (causal relationship with orlistat intake or pathophysiological mechanisms of development have not been established) were described.

Cases of decreased prothrombin, increased international normalized ratio (INR) values and unbalanced anticoagulant therapy have been reported during concomitant use of orlistat with indirect acting anticoagulants which resulted in changes in hemostatic parameters.

Cases of rectal bleeding, diverticulitis, pancreatitis, cholelithiasis and oxalate nephropathy have been reported (incidence not known). When concomitant use of orlistat and antiepileptic drugs there have been cases of seizures (see section “Interaction with other medicinal products”).

Overdose

In subjects with normal body weight and obese patients, administration of a single dose of 800 mg or multiple doses of orlistat 400 mg 3 times daily for 15 days was not accompanied by significant adverse events.

In addition, obese patients have experience of using orlistat at 240 mg 3 times/day for 6 months, which was not accompanied by a significant increase in the incidence of adverse events.

In cases of orlistat overdose, either no adverse events were reported or the adverse events did not differ from those observed when taking orlistat at therapeutic doses. In case of severe orlistat overdose it is recommended to observe the patient for 24 hours.

According to studies in humans and animals, any systemic effects that could be attributed to the lipase-inhibitory properties of orlistat should be reversed quickly.

Similarities

Xenical, Orsotene, Orsotene Slim, Listata, Listata Mini, Orlistat