Xenalten - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 98.64 mg, carboxymethyl starch sodium (sodium starch glycolate) 10.08 mg, sodium lauryl sulfate 6.24 mg, povidone 5.04 mg;

Capsules, hard gelatin

body and cap capsule - titanium dioxide 2%, dye blue patented 0.0158%, gelatin - up to 100%].

Description:

Hard gelatin capsules No. 1 with a body and a lid of a blue color.

The contents of the capsules are pellets of white or almost white color.

Pharmacotherapeutic group:Inhibitor of gastrointestinal tract lipases

ATX: & nbsp

A.08.A.B.01 Orlistat

Pharmacodynamics:

Orlistat is a specific and reversible inhibitor of gastrointestinal lipases, which has a prolonged action. Forms a covalent bond with the active serine region of the gastric and pancreatic lipases in the lumen of the stomach and small intestine. The inactivated enzyme loses the ability to break down food fats that come in the form of triglycerides (TG). Undivided TG is not absorbed, and the consequent 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.

But the results of the fat content in the feces, the action of orlistat begins within 24-48 hours after ingestion.After the drug is abolished, the fat content in the stool after 48-72 hours usually returns to the level that occurs before the start of therapy.

Orlistat is effective in terms of long-term control of body weight (reduction and maintenance of body weight, prevention of repeated weight gain) in patients with excessive body weight or obesity. Treatment with orlistat 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.

Patients with obesity. In clinical trials in patients taking orlistat, there was a large loss of body weight compared with patients on diet therapy. The decrease in body weight began already within the first 2 weeks after the beginning of treatment and lasted from 6 to 12 months even in patients with a negative response to diet therapy. For 2 years, there was a statistically significant improvement in the profile of metabolic risk factors associated with obesity.In addition, compared to taking placebo, there was 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, no more than 25% of the lost weight, was observed in about half of the patients, and half of these patients did not observe repeated weight gain or even further decrease.

Patients with obesity and type 2 diabetes mellitus. In clinical studies lasting from 6 months to 1 year in patients with overweight or obesity and type 2 diabetes mellitus orlistat, there was a large loss of body weight in comparison with patients treated only with diet therapy. The loss of body weight occurred mainly due to a decrease in the amount of fat in the body. It should be noted that before the study, despite the use of hypoglycemic agents, patients often had insufficient glycemic control. However, during the treatment with orlistat, a statistically and clinically significant improvement in glycemic control was observed.In addition, against the background of orlistat therapy, there was a decrease in doses of hypoglycemic agents, insulin concentrations, and a decrease in insulin resistance.

Reducing the risk of developing type 2 diabetes in obese patients. In a 4-year clinical trial, it was shown that orlistat significantly reduces the risk of developing type 2 diabetes (by about 37% compared with placebo). The degree of risk reduction was even more significant in patients with initial impairment of glucose tolerance (approximately 45%). In the treatment group, orlistat, there was a greater loss of body weight compared to the placebo group. Maintenance of body weight at a new level was observed throughout the study period. Moreover, compared with placebo in patients receiving orlistat therapy, there was a significant improvement in the profile of metabolic risk factors.

Pubertal obesity. In clinical studies of 1 year duration in adolescents with obesity, when taking orlistat, there was a decrease in body mass index (BMI), fat mass, and waist and hip circumference as compared to the placebo group.Also, patients who received orlistat therapy had a significant reduction in diastolic blood pressure compared with the placebo group.

Pharmacokinetics:

Suction. Absorption of orlistat is minimal. After taking therapeutic doses of orlistat, identify unchanged orlistat In plasma it was possible only in rare cases, and its concentrations were extremely small (<10 ng / ml). Signs of cumulation were absent, which confirms that orlistat absorption is minimal.

Distribution. The volume of distribution can not be determined, because orlistat very poorly absorbed. In vitro orlistat more than 99% associated with plasma proteins, mainly with lipoproteins and albumin. Orlistat in a minimum amount of penetrates into the red blood cells.

Metabolism. Orlistat is metabolized mainly in the intestinal wall with the formation of pharmacologically inactive metabolites M1 (hydrolyzed four-membered lactone ring) and M3 (M1 with the cleaved residue of N-formylleucine). In a study in obese patients, it was found that these two main metabolites accounted for about 42% of that minimal orlistat fraction that undergoes systemic absorption.

Excretion. The main way of elimination is the removal of non-sucking orlistat through the intestine. About 97% of the dose of orlistat was withdrawn through the intestine, 83% in the form of unchanged orlistat.

The total excretion of all metabolites by the kidneys is less than 2% of the dose taken. Orlistat and its metabolites M1 and M3 also undergo excretion through the intestine. The time to complete excretion (by the kidneys and through the intestine) is 3-5 days. The excretion of orlistat was similar in patients with normal body weight and with obesity. Pharmacokinetics in specific patient groups

Plasma concentrations of orlistat and its metabolites (M1 and M3) in children do not differ from those in adults when comparing identical doses of the drug. The daily excretion of fat through the intestine is 27% of the intake with food during orlistat therapy and 7% - when taking placebo.

Indications:

Long-term therapy for obese patients (BMI ≥30 kg / m²) or patients with overweight (BMI ≥28 kg / m²), including those associated with obesity risk factors, combined with a moderate hypocaloric diet. In combination with hypoglycemic drugs (metformin, sulfonylureas and / or insulin derivatives) or a moderately hypocaloric diet in patients with type 2 diabetes mellitus with overweight or obesity.

Contraindications:

Hypersensitivity to orlistat or other components of the drug.

Syndrome of chronic malabsorption.

Cholestasis.

Violation of liver function, impaired renal function (efficacy and safety not studied).

Simultaneous use with acarbose is not recommended.

Pregnancy and the period of breastfeeding.

Children under 12 years.

Carefully:

Simultaneous use with cyclosporine, amiodarone, antiepileptic drugs, levothyroxine sodium, warfarin or other oral aptycoagulants, age to 18 years.

Pregnancy and lactation:

The use of orlistat is contraindicated during pregnancy due to the lack of reliable clinical data confirming the safety of its use.

The penetration of orlistat into breast milk has not been studied, so its use is contraindicated during breastfeeding. If you need to use the drug during breastfeeding, breastfeeding should be discontinued.

Dosing and Administration:

Inside, with each main meal (during meals or no later than 1 hour after eating), with water.

If food intake is missed or if the food does not contain fat, Xenalten® can also be taken.

The drug Xenalten® 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 divided into three main meals.

Long-term therapy for obese patients (BMI ≥30 kg /m²) or patients with an overweight (BMI ≥28 kg /m²), including those who had associated with obesity risk factors, combined with a moderately hypocaloric diet:

in adults and children over 12 years, the recommended dose of orlistat is 120 mg (1 capsule) 3 times a day with each main meal or at least 1 hour after meals.

In combination with hypoglycemic drugs or moderately hypocaloric diet in patients with type 2 diabetes mellitus with excessive body weight or obesity:

In adults, the recommended dose of orlistat is 120 mg (1 capsule) 3 times a day with each major intake of the food or no later than 1 hour after eating.Increasing the dose of orlistat over the recommended (120 mg 3 times a day) does not lead to an increase in its therapeutic effect.

The efficacy and safety of Xenalten® in patients with impaired liver and / or kidney function, as well as in elderly and children (under 12 years) have not been studied.

Side effects:

Undesirable reactions in the use of orlistat mainly arose from the gastrointestinal tract and were due to the pharmacological action of orlistat, which prevents the absorption of food fats.

The frequency of undesired reactions is as follows: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥1 / 10000 and <1/1000 cases) and very rarely (<1/10000 cases).

Disorders from the gastrointestinal tract: Very often - oily discharge from the rectum, discharge of gas with a certain amount of discharge, urgency to defecate, steatorrhea, increased frequency of bowel movements, diarrhea, flatulence, pain or discomfort in the abdomen.

As a rule, these undesirable reactions are mild and transient, occur in the first three months. The frequency of these unwanted reactions increases with increasing fat content in the diet.Patients should be informed about the possibility of occurrence of these undesirable reactions and teach how to eliminate them by better adherence to the diet, especially regarding the amount of fat contained in it.

Often - bloating, "soft" stool, pain or discomfort in the rectum, fecal incontinence, tooth damage, gum lesion.

Disturbances from the nervous system: very often - headaches.

Disturbances from the respiratory system, chest and mediastinal organs: very often - infections of the upper respiratory tract; often - infection of the lower respiratory tract.

Disorders from the kidneys and urinary tract: often - urinary tract infections.

Immune system disorders: rarely - hypersensitivity reactions (itching, urticaria, rash, angioedema, bronchospasm, anaphylaxis).

Disturbances from the skin and subcutaneous tissues: very rarely - bullous rash. Disorders from the liver and bile ducts: very rarely - hepatitis (cause-and-effect relationship with orlistat reception is not established).

Violations of the genitals and mammary gland: often - dysmenorrhea.Laboratory and instrumental data: very rarely - increased activity of transaminases and alkaline phosphatase.

Disorders from the metabolism and nutrition: very often - hypoglycemia (in patients with type 2 diabetes mellitus).

Disorders of the psyche: often - an alarm.

Infectious and parasitic diseases: very often - the flu.

General disorders and disorders at the site of administration: often - weakness.

Cases of seizures (with simultaneous use with antiepileptic drugs), a decrease in prothrombin, an increase in INR (with simultaneous use with anticoagulants), rectal bleeding, diverticulitis, pancreatitis, cholelithiasis and oxalate nephropathy have been reported in the postmarketing period (incidence is unknown).

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> 2% and incidence> 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.

If any of the unwanted reactions listed in the manual is aggravated, or if you notice other undesirable reactions not listed in the instructions, inform the doctor about it.

Overdose:

A single oral intake of 800 mg of orlistat or when administered at a dose of up to 400 mg three times daily for 15 days by people with normal body weight and with obesity was not accompanied by 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 overdose of orlistat, either the absence of undesirable events was reported, or the undesirable events did not differ from those. which are observed when the drug is used in therapeutic doses.

In case of overdose, see a doctor. In severe overdose of orlistat, the patient should be monitored for 24 hours. According to studies in humans and animals, any systemic effects that can be associated with lipase inhibitory properties of orlistat must be quickly reversible.

Interaction:

With the simultaneous administration of orlistat and cyclosporine, there was a decrease in the concentration of cyclosporine in the blood plasma, so a more frequent determination of the concentration of cyclosporine in the blood plasma is recommended while taking orlistat and cyclosporine. In the case of simultaneous application of orlistat and cyclosporine, a continuous monitoring of the concentration of cyclosporine in the blood plasma is necessary, since a decrease in its plasma concentration is possible.

It is not recommended simultaneous application of orlistat and acarbose, due to the lack of data on pharmacokinetic interactions.

With the simultaneous use of orlistat and anticoagulants, there have been cases of a decrease in prothrombin, an increase in the values of the international normalized ratio (INR) and unbalanced anticoagulant therapy, which led to a change in the haemostatic parameters.Therefore, with the simultaneous use of warfarin or other indirect anticoagulants with orlistat, monitoring of INR indicators is necessary.

With the simultaneous reception with orlistatom reduces the absorption of fat-soluble vitamins A, D, E and K. If recommended multivitamins, they should be taken no less than 2 hours after taking orlistat or before bedtime.

With the simultaneous use of amiodarone and orlistat, the systemic exposure of amiodarone and desethylamiodarone decreased, but due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is unclear. With the simultaneous use of orlistat with amiodarone, clinical observation of the patient and monitoring of the electrocardiogram are recommended.

With the simultaneous use of orlistat and antiepileptic drugs, there have been cases of seizures. Causal relationship between the development of seizures and orlistat therapy is not established. However, patients should be monitored for possible changes in the frequency and / or severity of the convulsive syndrome.

With the simultaneous use of orlistat with levothyroxine sodium hypothyroidism and / or a decrease in the control of hypothyroidism may develop,which may be due to a decrease in absorption of inorganic iodine and / or levothyroxine sodium.

There was no interaction of orlistat with amitriptyline, atorvastatin. biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, nifedipine, sibutramine and ethanol.

In some cases orlistat can indirectly reduce the bioavailability of oral contraceptives. In the case of diarrhea, the use of an additional method of contraception is recommended.

Special instructions:

During the treatment period, a balanced, low-calorie diet containing no more than 30% of calories in the form of fats and enriched with fruits and vegetables should be observed.

The daily intake of fats, carbohydrates and proteins must be divided into three main meals.

The likelihood of adverse reactions from the gastrointestinal tract increases when orlistat is used with food containing a large amount of fat (more than 30% of the daily calorific value). In clinical studies in most patients, concentrations of vitamins A, D, E, K and beta-carotene during 4 years of orlistat therapy remained normal. To ensure adequate intake of minerals and vitamins, multivitamins.

Since weight loss is usually accompanied by an improvement in carbohydrate metabolism, patients with type 2 diabetes should consult a physician to adjust the dose of hypoglycemic drugs if necessary.

Decreased body weight during treatment can be accompanied by a decrease in blood pressure and cholesterol concentration. Patients taking drugs for the treatment of hypertension and hypercholesterolemia should consult a physician to adjust the doses of the above drugs if necessary.

Although there was no interaction between orlistat and oral contraceptives, orlistat can indirectly reduce bioavailability of oral contraceptives, which can lead to the development of unwanted pregnancies. It is recommended to use additional types of contraception in case of acute diarrhea.

Simultaneous use of orlistat with amiodarone, antiepileptic drugs,levothyroxine sodium, warfarin, or other oral anticoagulants is possible only after consultation with a physician (see section "Interaction with other drugs").

The use of orlistat simultaneously with cyclosporine or acarbose is not recommended and requires consultation with a physician.

Patients with kidney disease, before taking orlistat should consult with a doctor, as it is possible to develop hyperoxalaturia and nephropathy.

Patients should stop taking orlistat and consult a doctor if symptoms such as icteric staining of the sclera or skin, darkening of the urine and loss of appetite occur.

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

Orlistat does not affect the ability to drive vehicles and perform work that requires increased attention and speed of psychomotor reactions. Patients with type 2 diabetes mellitus who use orlistat 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:

Capsules 120 mg.

Packaging:

For 7 or 21 capsules in a contour cell box made of a polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 4 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003057

Date of registration:25.06.2015 / 10.11.2015

Expiration Date:25.06.2020

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp05.02.2018

Illustrated instructions

Instructions

Xenalten® (Kcenalten®)