Orlistat

General characteristics. Structure:

Active ingredient: 120 mg of an orlistat in 1 capsule.

Excipients: cellulose microcrystallic, sodium carboxymethylstarch (sodium of starch glikolit), sodium lauryl sulfate, povidone, talc.

Gelatinous solid capsules (titanium dioxide, gelatin, dye blue patent). 

Pharmacological properties:

Pharmacodynamics. Specific inhibitor of gastrointestinal lipases. Forms a covalent bond with the active serinovy site of gastric and pancreatic lipases in a gleam of a stomach and small intestine. The inactivated enzyme loses ability to split the food fats arriving in the form of triglycerides (TG). Not split TG are not soaked up, and arising thereof reduction of receipt of calories in an organism leads to a body degrowth. Increases concentration of fat in fecal masses in 24-48 h after reception. Provides effective control of body weight, reduction of depot of fat.

Manifestation of activity does not require system absorption of an orlistat, in the recommended therapeutic dose (120 mg 3 times a day) it approximately for 30% inhibits absorption of the fats arriving with food.

Pharmacokinetics. Absorption - low; by 8 h after intake not changed орлистат in plasma is not defined (concentration lower than 5 ng/ml).

System exposure of an orlistat is minimum. After intake of 360 mg it is radioactive a marked 14C-orlistat the radioactivity peak in plasma was reached approximately in 8 h; concentration of not changed orlistat was close to a definition limit (less than 5 ng/ml). In the therapeutic researches including the monitoring of samples of plasma of patients which is not changed орлистат was defined in plasma sporadic, and its concentration were low (less than 10 ng/ml), without accumulation signs that it will be coordinated with the minimum absorption of drug.

In vitro орлистат more than for 99% contacts proteins of plasma, generally lipoproteins and albumine. Orlistat minimum gets into erythrocytes. Also the M3 is metabolized mainly in a GIT wall with formation pharmacological of inactive metabolites of M1 (the hydrolyzed four-membered lactonic ring) (M1 with the chipped-off N-formylleucine rest).

In a research at the patients with obesity accepting inside 14C-orlistat on 2 metabolite, about 42% of the general radioactivity of plasma were necessary to M1 and M3. M1 and M3 have an open beta and lactonic ring and show extremely weak inhibiting activity concerning lipases (in comparison with orlistaty more weakly in 1000 and 2500 times respectively). Considering low activity and low concentration of metabolites in plasma (about 26 ng/ml and 108 ng/ml for M1 and M3 respectively in 2-4 h after reception of an orlistat in therapeutic doses), these metabolites are considered pharmacological as insignificant.

The main metabolite of M1 has short T1/2 (about 3 h), the second metabolite is removed more slowly (T1/2 is 13,5 h). At patients with obesity of Css of a metabolite of M1 (but not M3) increases in proportion to a dose of an orlistat. After a single dose in 360 mg of a 14C-orlistat patients with normal body weight and having obesity, allocation of not soaked up orlistat through intestines was the main way of removal. Orlistat and his metabolites of M1 and M3 are also exposed to excretion with bile. About 97% of entered are radioactive marked substance 83% - in not changed look were removed with excrements, including.

Cumulative renal excretion of the general radioactivity at reception of 360 mg of a 14C-orlistat made less than 2%. Time of full elimination with excrements and urine - 3-5 days. Removal of an orlistat was similar at patients with normal body weight and with obesity. On the basis of limited data, T1/2 of the absorbed orlistat fluctuates within 1-2 h.

Indications to use:

- treatment of obesity, including reduction and maintenance of body weight, in combination with a hypocaloric diet;

- reduction of risk of a repeated increase of body weight after its initial decrease.

Orlistat is shown to patients with obesity at the body weight index (BWI) of ≥30 kg/sq.m or ≥28 kg/sq.m with other risk factors (a diabetes mellitus, arterial hypertension, a dislipidemiya).

(Calculation of IMT: IMT = M/P2, where M - body weight, kg; P - growth, l).

Route of administration and doses:

Inside, 120 mg (1 капс.) 3 times a day during each meal or not later than in 1 h after food (if food does not contain fat, then reception can be missed).

Features of use:

Pregnancy and lactation. Orlistat it is contraindicated to apply during pregnancy due to the lack of the reliable clinical data confirming safety of its use.

It is not established whether gets орлистат into breast milk in this connection drug use Orlistat during breastfeeding is not recommended.

During treatment it is necessary to keep to the balanced, low-calorie diet containing no more than 30% of a kalorazh in the form of fats and enriched with fruit and vegetables.

Before purpose of an orlistat it is necessary to exclude the organic reason of obesity, for example a hypothyroidism.

The probability of development of by-effects from a GIT increases at high content in food of fats (more than 30% of daily caloric content). Daily reception of fats, carbohydrates and proteins has to be distributed between three main meals.

As орлистат reduces absorption of some fat-soluble vitamins, for ensuring their adequate receipt in an organism patients have to accept the polyvitaminic drugs containing fat-soluble vitamins. Besides, the content of vitamin D and beta carotene at patients with obesity can be lower, than at the people who do not have obesity.

Polyvitamins should be taken for 2 h to or in 2 h after reception of an orlistat, for example before going to bed. At the patients who were not receiving preventively vitamin supplements at two and more consecutive visits to the doctor for first and second treatments orlistaty lowering of the level of vitamins B to plasma was recorded.

As absorption of vitamin K at reception of an orlistat can decrease, at the patients receiving орлистат against the background of long constant reception of warfarin it is necessary to control blood coagulation parameters.

Reception of an orlistat in the doses exceeding 120 mg 3 times a day does not provide additional effect.

If the concomitant use of an orlistat with cyclosporine cannot be avoided, continuous monitoring of content of cyclosporine in plasma is necessary.

At some patients against the background of an orlistat the maintenance of oxalates in urine can increase. As well as for other drugs for a body degrowth, some groups of patients (for example with nervous anorexia or bulimia) have a probability of abuse orlistaty.

Induction orlistaty losses of body weight can be combined with improvement of metabolic control of a diabetes mellitus that will demand reduction of doses of peroral hypoglycemic means (derivative sulphonylurea, Metforminum) or insulin. If If after 12 weeks of therapy by drug Orlistat decrease in body weight made less than 5% of initial, consultation of the doctor is necessary for the solution of a question of need of continuation of treatment orlistaty.

Treatment should not continue more than 2 years.

Orlistat is not intended for use in children's practice.

Influence on ability to manage vehicles and mechanisms. Does not exert impact on ability to control of vehicles and to service of moving mechanisms.

Side effects:

Frequency of the side reactions given below was defined according to the following: very often (> 1/10); often (> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages.

From a GIT: very often - oily allocations from a rectum, release of gases with a quantity separated, imperative desires on defecation, a steatorrhea, defecation increase, a liquid chair, a meteorism, pains or discomfort in a stomach.

As a rule, the specified side reactions are slight and tranzitorny, arise at early stages of treatment (in the first 3 months). Frequency of these undesirable reactions increases at increase in content of fat in food. Patients should be informed on possibility of the specified side reactions and to train how to eliminate them by the best observance of a diet, especially concerning amount of the fat which is contained in it. Often - a soft chair, pains or discomfort in a rectum, an incontience a calla, abdominal distention, damage of teeth, damage of gums.

From respiratory system, bodies of a thorax and a mediastinum: very often - upper respiratory tract infections, it is frequent - lower respiratory tract infections.

From immune system: seldom - an itch, urticaria, rash, a Quincke's disease, a bronchospasm, an anaphylaxis.

From a nervous system: very often - headaches.

From a liver and biliary tract: very seldom - increase in activity of transaminases and ShchF, hepatitis.

From kidneys and urinary tract: often - infections of urinary tract.

Others: very often - flu; often - a dysmenorrhea, alarm, weakness.

If any of the side effects specified in the instruction are aggravated or any other side effects which are not specified in the instruction are noticed, it is necessary to report about it to the doctor.

Interaction with other medicines:

Orlistat does not influence pharmacokinetics of the ethanol, digoxin (appointed in a single dose) and Phenytoinum (appointed in a single dose of 300 mg), bioavailability of nifedipine (a tablet of the prolonged release). Ethanol does not influence a pharmacodynamics (excretion of fats with a stake) and system exposure of an orlistat.

At simultaneous use of an orlistat and cyclosporine the level of the last in plasma goes down (орлистат and cyclosporine should not be accepted at the same time; for reduction of probability of medicinal interaction cyclosporine should be taken for 2 h to or in 2 h after reception of an orlistat).

At simultaneous use of warfarin or other indirect anticoagulants with orlistaty the level of a prothrombin can decrease and change value of an indicator of MNO therefore control of MNO is necessary. Orlistat reduces absorption of the beta carotene which is contained in nutritional supplements by 30% and inhibits vitamin E absorption (in the form of acetate tocopherol) approximately for 60%.

Increases bioavailability and hypolipidemic effect of a pravastatin, increasing its concentration in plasma for 30%.

At a concomitant use with orlistaty absorption of vitamins A, D, E and K decreases. If polyvitamins are recommended, it is necessary to accept them not less than in 2 h after administration of drug Orlistat or before going to bed.

Decrease in body weight can improve a metabolism at patients with a diabetes mellitus owing to what it is necessary to reduce a dose of peroral hypoglycemic HP.

Simultaneous use with acarbose due to the lack of data on pharmacokinetic interactions is not recommended. At simultaneous use with orlistaty reduction of level of Amiodaronum in plasma after a single dose is noted. Simultaneous use of an orlistat and Amiodaronum is possible only according to the recommendation of the doctor.

Orlistat can reduce indirectly bioavailability of oral contraceptives that can lead to development of undesirable pregnancy. It is recommended to use additional types of contraception in case of development of acute diarrhea.

Clinically significant interactions with digoxin, amitriptyline, Phenytoinum, fluoxetine, sibutraminy, atorvastatiny, pravastatiny, lozartany, Glibenclamidum, oral contraceptives, nifedipine, furosemide, captopril, atenololy and ethanol are noted.

Contraindications:

- hypersensitivity to an orlistat or other components of drug;

- sprue;

- cholestasia;

- a concomitant use with cyclosporine;

- pregnancy and feeding by a breast;

- age up to 18 years.

With care: existence of a hyperoxaluria in the anamnesis, nephrolithiasis (calcic oxalic stones).

Overdose:

Cases of overdose are not described. The single dose of 800 mg of an orlistat or its multiple dose in a dose to 400 mg 3 times a day within 15 days by people with normal body weight and with obesity was not followed by significant by-effects.

If the considerable overdose of an orlistat is revealed, it is necessary to watch a condition of the patient during 24 h. According to researches animals and the person, have to have quickly reversible the system effects connected with lipazoingibiruyushchy properties of an orlistat.

Storage conditions:

In the dry place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Capsules of 120 mg. Packaging: on 7 or 21 капс. in a blister strip packaging from the film of PVC and printing aluminum foil varnished. On 1, 2, 3, 4, 6, 12 blister strip packagings are placed in a pack from a cardboard.