Composition, form of production and packaging
Capsules number 1 with a body and a lid of blue color of white or almost white color; the contents of the capsules are granules.
Orlistat 120 mg
Excipients: microcrystalline cellulose 59.6 mg, carboxymethyl starch sodium (sodium krahamal glycolate) 38.0 mg, sodium lauryl sulfate 10.0 mg, povidone 10.0 mg, talc 2.4 mg.
Capsules hard gelatinous (titanium dioxide, gelatin, dye blue patented). The average weight of the contents of the capsule is 240 mg.
7 pcs. - Packings contour mesh (1) - packs cardboard.
7 pcs. - packings contour mesh (2) - packs cardboard.
7 pcs. - Packings contour mesh (3) - packs cardboard.
7 pcs. - packings contour mesh (6) - packs cardboard.
7 pcs. - Packings contour mesh (12) - packs cardboard.
21 pcs. - Packings contour mesh (1) - packs cardboard.
21 pcs. - packings contour mesh (2) - packs cardboard.
21 pcs. - Packings contour mesh (3) - packs cardboard.
21 pcs. - packings contour mesh (6) - packs cardboard.
21 pcs. - Packings contour mesh (12) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Specific inhibitor of gastrointestinal lipases. 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. Increases the concentration of fat in the stool after 24-48 hours after ingestion. Provides effective control of body weight, reduction of fat depot.
For the manifestation of activity, no systemic absorption of orlistat is required, at a recommended therapeutic dose (120 mg 3 times / day), it inhibits approximately 30% absorption of incoming fat from food.
Absorption is low; 8 hours after ingestion, unchanged orlistat in plasma is not detected (concentration below 5 ng / ml).
The systemic exposure of orlistat is minimal. After ingestion of 360 mg radioactively labeled 14 C-orlistat, the radioactivity peak in the plasma was reached after about 8 hours; the concentration of unchanged orlistat was close to the detection limit (less than 5ng / ml). In therapeutic studies involving monitoring of plasma samples of patients, unchanged orlistat was detected sporadically in plasma and its concentrations were low (less than 10 ng / ml), with no evidence of accumulation, consistent with minimal absorption of the drug.
In vitro, orlistat more than 99% binds to plasma proteins, mainly lipoproteins and albumin. Orlistat minimally penetrates into the red blood cells. Metabolized mainly in the wall of the gastrointestinal tract (GIT) with the formation of pharmacologically inactive metabolites Ml (hydrolyzed four-membered lactone ring) and M3 (M1 with the cleaved N-formylleucine residue). In a study in obese patients who ingested 14 C-orlistat, two metabolites, Ml and M3, accounted for about 42% of the total radioactivity of the plasma. Ml and M3 have an open beta-lactone ring and show extremely weak inhibitory activity against lipases (compared with orlistat weaker 1000 and 2500 times, respectively). Considering the low activity and low concentration of metabolites in plasma (about 26 ng / ml and 108 ng / ml for Ml and MZ respectively 2-4 hours after taking orlistat at therapeutic doses), these metabolites are considered pharmacologically insignificant. The main metabolite Ml has a short half-life (T 1/2) (about 3 h), the second metabolite is slower (T 1/2 - 13.5 h). In obese patients, the equilibrium concentration (Css) of the metabolite Ml (but not M3) increases in proportion to the dose of orlistat. After a single oral intake of 360 mg of 14 C-orlistat by patients with normal body weight and obese, excretion of unsweetened orlistat through the intestine was the main route of excretion. Orlistat and its metabolites Ml and M3 also undergo excretion with bile. About 97% of the radiolabeled substance introduced was excreted with feces, incl. 83% - unchanged.
The total renal excretion of total radioactivity when taking 360 mg of 14 C-orlistat was less than 2%. The time of complete elimination with feces and urine is 3-5 days. The excretion of orlistat was similar in patients with normal body weight and with obesity. Based on the limited data, T 1/2 of the absorbed orlistat fluctuates within 1-2 hours.
Treatment of obesity, incl. reduction and maintenance of body weight, in combination with a hypocaloric diet.
Orlistat is also indicated to reduce the risk of repeated weight gain after its initial decline.
Orlistat is indicated in obese patients with a body mass index (BMI)> 30 kg / m 2 or> 28 kg / m 2 in the presence of other risk factors (diabetes, hypertension, dyslipidemia).
(Calculation of BMI: BMI = M / P 2 , where M - body weight, kg, P - height, m)
Inside, 120 mg (1 capsule) 3 times / day during each meal or not later than 1 hour after a meal (if the food does not contain fat, then you can skip reception).
The incidence of adverse reactions listed below was determined as follows: very often> 1/10; often> 1/100, <1/10; sometimes> 1/1000, <1/100; rarely> 1/10 000, <1/1000; very rarely <1/10 000, including individual messages.
On the part of the gastrointestinal tract: very often - oily discharges from the rectum, the release of gases with a certain amount of detachable, mandatory urges for defecation, steatorrhoea, frequent bowel movements, loose stools, flatulence, pain or discomfort in the abdomen. As a rule, these adverse reactions are mild and transient, occur at early stages of treatment (in the first 3 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 adverse reactions and teach how to eliminate them by better adherence to the diet, especially regarding the amount of fat contained in it. Often - a soft stool, pain or discomfort in the rectum, fecal incontinence, bloating, dental damage, gum disease.
On the part of the respiratory system, chest and mediastinum: very often - infections of the upper respiratory tract; often - infection of the lower respiratory tract.
From the immune system: rarely - itching, urticaria, rash, angioedema, bronchospasm, anaphylaxis.
From the nervous system: very often - headaches.
From the liver and bile ducts: very rarely - increased activity of transaminases and alkaline phosphatase, hepatitis.
From the side of the kidneys and urinary tract: often - urinary tract infections.
Other: very often - influenza; often - dysmenorrhea, anxiety, weakness.
If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform your doctor.
- hypersensitivity to orlistat or other components of the drug;
- malabsorption syndrome;
- simultaneous administration with cyclosporine;
- age to 18 years.
With caution in the presence of hyperoxaluria in the anamnesis, nephrolithiasis (calcium oxalate stones).
PREGNANCY AND LACTATION
Orlistat is contraindicated to be used during pregnancy due to the lack of reliable clinical data confirming the safety of its use.
It is not established whether orlistat penetrates into breast milk, and therefore the use of Xenalten during breast-feeding is not recommended.
APPLICATION FOR CHILDREN
Xenalten is not intended for use in children's practice.
During the treatment it is necessary to observe a balanced, low-calorie diet containing no more than 30% of calories in the form of fats and enriched with fruits and vegetables (optional addition of multivitamins to compensate for reduced absorption of fat-soluble vitamins).
Before the appointment of orlistat should be deleted organic cause of obesity, for example hypothyroidism.
The likelihood of side effects from the gastrointestinal tract increases with a high content of fat in the diet (more than 30% of daily calories). Daily intake of fats, carbohydrates and proteins should be distributed among the three main meals. Since orlistat reduces the absorption of some fat-soluble vitamins, patients must take multivitamin preparations containing fat-soluble vitamins to ensure their adequate intake. In addition, the content of vitamin D and beta-carotene in obese patients may be lower than in people who are not obese. Multivitamins should be taken 2 hours before or 2 hours after taking orlistat, for example, before going to bed. The intake of orlistat in doses exceeding 120 mg 3 times / day does not provide an additional effect.
If simultaneous intake of orlistat with cyclosporine is not possible, continuous monitoring of cyclosporin content in plasma is necessary.
In patients who did not receive prophylactic vitamin supplements, with two or more consecutive visits to the doctor during the first and second years of treatment with orlistat, a decrease in the level of vitamins in plasma was recorded.
In some patients, the content of oxalate in urine may increase with orlistat.
As with other drugs to reduce body weight, in some groups of patients (for example, with anorexia nervosa or bulimia), there is a possibility of abuse of orlistat.
Since the absorption of vitamin K can be reduced when taking orlistat, patients who receive orlistat with long-term continuous use of warfarin should monitor the parameters of blood clotting.
Orlistat's induction of weight loss can be combined with an improvement in the metabolic control of diabetes mellitus, which will require a reduction in the doses of oral hypoglycemic agents (sulfonylureas, metformin, etc.) or insulin.
If, after 12 weeks of therapy with Xenalten, a decrease in body weight is less than 5% of the original, a doctor's consultation is needed to decide whether to continue treatment with orlistat.
Treatment should not last more than 2 years.
Xenalten is not intended for use in children's practice.
Impact on the ability to drive vehicles and manage mechanisms
Does not affect the ability to drive vehicles and service moving machinery.
Cases of overdose are not described.
A single dose of 800 mg of orlistat or its repeated administration in a dose of up to 400 mg 3 times / day for 15 days by people with normal body weight and with obesity was not accompanied by significant side effects.
If a significant overdose of orlistat is found, the patient should be monitored for 24 hours. According to animal and human studies, systemic effects associated with the lipaspptive properties of orlistat should be rapidly reversible.
Orlistat does not affect the pharmacokinetics of ethanol, digoxin (prescribed in a single dose) and phenytoin (prescribed in a single dose of 300 mg), on the bioavailability of nifedipine (sustained-release tablets). Ethanol does not affect pharmacodynamics (excretion of fats with feces) and systemic exposure of orlistat.
With the simultaneous use of orlistat and cyclosporin, the plasma level decreases in the plasma (orlistat and cyclosporine should not be taken at the same time, to reduce the likelihood of drug interaction, cyclosporine should be taken 2 hours before or 2 hours after taking orlistat).
With the simultaneous use of warfarin or other indirect anticoagulants with orlistat, the level of prothrombin can decrease and the value of the indicator of the international normalized ratio (MHO) may change, therefore MHO control is necessary.
Orlistat reduces the absorption of beta-carotene contained in food additives by 30% and inhibits the absorption of vitamin E (in the form of tocopherol acetate) by approximately 60%.
Increases the bioavailability and hypolipidemic effect of pravastatin, increasing its concentration in plasma by 30%.
At simultaneous reception with orlistatom absorption of vitamins A, D, E and K decreases. If multivitamins are recommended, they should be taken no less than 2 hours after taking Xenalten or before bedtime.
Decreased body weight can improve metabolism in diabetic patients, and as a result, it is necessary to reduce the dose of oral hypoglycemic drugs.
It is not recommended simultaneous use with acarbose due to the lack of data on pharmacokinetic interactions.
With simultaneous use with orlistatom a decrease in the level of amiodarone in the plasma after a single dose. Simultaneous use of orlistat and amiodarone is possible only on the advice of a doctor.
Orlistat may indirectly reduce the 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.
Clinically significant interactions with digoxin, amitriptyline, phenytoin, fluoxetine, sibutramine, atorvastatin, pravastatin, nifedipine, losartan, glibenclamide, furosemide, captopril, atenolol, and ethanol were not noted.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light and out of reach of children at a temperature of no higher than 25 В° C.
Shelf life - 2 years. Do not use after the expiry date printed on the package.