Listata 120 mg, 40 film-coated tablets
Registration Certificate Holder
IZVARINO PHARMA (Russia)
Dosage form
Medicine - Listata
Description
Film-coated tablets
blue with a mother-of-pearl effect, oval, biconvex, with a mark on one side and the symbol “f” on the other; on a cross section, the core is white or almost white.
1 tab.
orlistat 120 mg
Excipients
: sodium lauryl sulfate - 12 mg, acacia gum - 210 mg, mannitol - 580 mg, crospovidone - 50 mg, magnesium stearate - 8 mg.
Shell composition:
opadry II blue (85F205040) - 34 mg, incl. polyvinyl alcohol - 40%, titanium dioxide - 22.48%, macrogol 3350 - 20.20%, talc - 14.8%, blue aluminum varnish - 2.28%, yellow iron oxide dye - 0.24%; opadry silver (63F97546) - 6 mg, incl. polyvinyl alcohol - 47.03%, talc - 27%, macrogol 3350 - 13.27%, pearlescent pigment - 10%, polysorbate-80 - 2.7%.
10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (6) — cardboard packs. 10 pieces. — contour cell packaging (9) — cardboard packs.
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, 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.
Contraindications for use
- hypersensitivity sensitivity to orlistat or any other components of the drug;
- chronic malabsorption syndrome;
- cholestasis;
- pregnancy, breastfeeding period;
- children's age up to 12 years.
pharmachologic effect
Pharmacodynamics
Orlistat is a potent, specific and reversible inhibitor of gastrointestinal lipases with a long-lasting effect. Its therapeutic effect occurs in the lumen of the stomach and small intestine and consists of the formation of a covalent bond with the active serine site of gastric and pancreatic lipases.
The inactivated enzyme then loses the ability to break down food fats, which come in the form of triglycerides, into absorbable free fatty acids and monoglycerides. Since unsplit 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 circulation.
Based on fecal fat results, the effects of orlistat begin 24 to 48 hours after dosing. After discontinuation of orlistat, fecal fat content usually returns to pre-therapy levels within 48-72 hours.
Clinical effectiveness
Patients taking orlistat experience greater weight loss compared to patients on diet therapy. Body weight loss begins within the first 2 weeks after the start of treatment and continues from 6 to 12 months, even in patients with a negative response to diet therapy. Over the course of 2 years, there was a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, compared to placebo, there was a significant reduction in body fat. Orlistat is effective in preventing weight gain. Re-gain of body weight, no more than 25% of lost, is observed in approximately half of the patients, and in half of these patients, re-gain of body weight is not observed or even a further decrease is observed.
Overweight or obese patients with type 2 diabetes mellitus treated with orlistat for 6 months to 1 year experienced greater weight loss compared with patients receiving dietary therapy alone. Weight loss occurs mainly due to a decrease in the amount of fat in the body. With orlistat therapy, a statistically and clinically significant improvement in glycemic control is observed. In addition, during therapy 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 mellitus is significantly reduced (by approximately 37% compared to placebo). The degree of risk reduction is even greater in patients with baseline impaired glucose tolerance (approximately 45%).
Maintaining body weight at a new level is observed throughout the entire period of use of the drug.
When orlistat was used for 1 year in obese adolescents, there was a decrease in BMI, a decrease in fat mass, and a decrease in waist and hip circumference compared to the placebo group. Also, patients treated with orlistat showed a significant decrease in diastolic blood pressure compared to the placebo group.
Drug interactions
There were no interactions of orlistat with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine GITS (gastrointestinal therapeutic system) and nifedipine slow release, sibutramine or ethanol (on based on drug interaction studies). However, it is necessary to monitor INR values during simultaneous therapy with warfarin or other indirect anticoagulants.
When taken simultaneously with orlistat, a decrease in the absorption of vitamins D, E and beta-carotene was observed. If multivitamins are recommended, they should be taken at least 2 hours after taking orlistat or at bedtime.
When taking orlistat and cyclosporine together, a decrease in the concentration of cyclosporine in the blood plasma was observed, therefore, more frequent determination of the concentration of cyclosporine in the blood plasma is recommended when taking cyclosporine and orlistat simultaneously.
When amiodarone was taken orally during orlistat therapy, a decrease in the systemic exposure of amiodarone and desethylamiodarone was observed (by 25-30%), however, due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is not clear. Adding orlistat to long-term amiodarone therapy may result in a decrease in the therapeutic effect of amiodarone (no studies have been conducted).
Concomitant use of orlistat and acarbose should be avoided due to the lack of pharmacokinetic study data.
Cases of seizures have been observed when taking orlistat and antiepileptic drugs simultaneously. A cause-and-effect relationship between the development of seizures and orlistat therapy has not been established. However, patients should be monitored for possible changes in seizure frequency and/or severity.
Dosage regimen
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 low-calorie diet
Adults and children over 12 years old
The recommended dose of Listata is 1 tablet. (120 mg) with each main meal (during meals or no later than 1 hour after meals).
In combination with hypoglycemic drugs (metformin, sulfonylureas 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 (during meals or no later than 1 hour after meals).
If a meal is skipped or if the meal does not contain fat, then Listata can also be skipped.
Listata should be taken in combination 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 must be distributed between 3 main meals.
Increasing the dose of Listat above the recommended dose (120 mg 3 times a day) does not increase its therapeutic effect.
The effectiveness 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.
Overdose
In individuals with normal body weight and obese patients, single doses of 800 mg or repeated doses of orlistat 400 mg 3 times a day for 15 days were not accompanied by the occurrence of significant adverse events. In addition, obese patients have experience using 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 orlistat overdose, either no adverse events were 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 inhibitory properties of orlistat should be quickly reversible.
Side effect
Clinical trial data
Side effects of the drug are systematized in relation to each organ system 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); uncommon (more than 1/1000, less than 1/100); rare (more than 1/10,000, less than 1/1000); very rare, including isolated messages (less than 1/10,000). Adverse reactions when using orlistat occurred mainly from the gastrointestinal tract and were due to the pharmacological effect of orlistat, which interferes with the absorption of dietary fats. Very often, phenomena such as oily discharge from the rectum, the release of gases with some discharge, an imperative urge to defecate, steatorrhea, increased frequency of bowel movements, loose stools, flatulence, pain or discomfort in the abdomen were noted. Their frequency increases with increasing fat content in food. Patients should be informed of the possibility of gastrointestinal adverse reactions and taught how to manage them with diet, especially in relation to the amount of fat it contains. Adopting a low-fat diet reduces the likelihood of gastrointestinal side effects and thereby helps patients control and regulate their fat intake.
As a rule, these adverse 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, dental damage, gum damage. Also noted very often were headaches, upper respiratory tract infections, and flu; 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 overweight and obese individuals without diabetes mellitus. The only new adverse events in patients with type 2 diabetes were hypoglycemic conditions, occurring at an incidence greater than 2% and an incidence of at least 1% compared with placebo (which may have resulted from improved carbohydrate compensation), and frequently, abdominal bloating.
In the 4-year clinical study, the overall safety profile did not differ from that obtained in the 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 have been described, 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 isolated, possibly serious cases of hepatitis have been described (a cause-and-effect relationship with taking orlistat or pathophysiological mechanisms of development have not been established).
With the simultaneous use of orlistat with indirect anticoagulants, cases of decreased prothrombin, increased international normalized ratio (INR) values, and unbalanced anticoagulant therapy have been reported, which led to changes in hemostatic parameters.
Cases of rectal bleeding, diverticulitis, pancreatitis, cholelithiasis and oxalate nephropathy have been reported (incidence unknown).
Cases of seizures have been observed when taking orlistat and antiepileptic drugs simultaneously (see section “Interaction with other drugs”).
special instructions
Listata is effective in long-term weight control (weight loss and maintenance, prevention of weight gain). Treatment with Listata leads to an improvement in the profile of risk factors and diseases associated with obesity, including hypercholesterolemia, type 2 diabetes mellitus, impaired glucose tolerance, hyperinsulinemia, arterial hypertension, and a decrease in the amount of visceral fat.
When used in combination with hypoglycemic drugs such as metformin, sulfonylureas and/or insulin in patients with type 2 diabetes mellitus who are overweight (BMI at least 28 kg/m2) or obese (BMI at least 30 kg/m2), Listata in combination with a moderately hypocaloric diet further improves the compensation of carbohydrate metabolism.
In clinical studies, the majority of patients had concentrations of vitamins A, D, E, K and beta-carotene within the normal range during 4 years of orlistat therapy. To ensure adequate intake of all minerals, multivitamins can be taken.
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 must be divided into three main meals. The likelihood of adverse reactions from the gastrointestinal tract may increase if Listata is taken on a diet rich in fat (for example, 2000 kcal/day, of which more than 30% in the form of fat, which equals approximately 67 g of fat). If Listata is taken with a meal very rich in fat, the likelihood of gastrointestinal reactions increases.
In patients with type 2 diabetes mellitus, weight loss during treatment with Listata is accompanied by improved compensation of carbohydrate metabolism, which may allow or require a reduction in the dose of hypoglycemic drugs (for example, sulfonylurea derivatives).
Effect on the ability to drive vehicles and machinery
Listata does not affect the ability to drive vehicles and machinery. Patients with type 2 diabetes mellitus using Listata in combination with hypoglycemic drugs should be careful when driving vehicles and machinery due to the possible development of hypoglycemia, accompanied by dizziness and blurred vision.
Storage conditions
The drug should be stored in a place protected from light and out of reach of children at a temperature not exceeding 25°C.
Best before date
Shelf life: 2 years.
Do not use after the expiration date.
Use during pregnancy and breastfeeding
Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.
In animal reproductive toxicity studies, no teratogenic or embryotoxic effects of orlistat were 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 excretion of orlistat in breast milk, the use of Listata during breastfeeding is contraindicated.
Use for renal impairment
Efficacy and safety of Listata in patients with impaired renal function.
Use for liver dysfunction
Efficacy and safety of Listata in patients with impaired liver function.
Use in elderly patients
Efficacy and safety of Listata in elderly patients
have not been studied.
Use in children
Restrictions for children - With caution.
The use of the drug is contraindicated in children under 12 years of age.
Terms of sale
The drug is available with a prescription.
Contacts for inquiries
IZVARINO PHARMA LLC (Russia)
142750 Moscow, Izvarino village, territory of VNTsMDL, building 1 Tel./fax, 232-56-54
