Orlistat - instructions for use, doses, side effects, contraindications

Orlistat	- 120 mg
Auxiliary substances:
[microcrystalline cellulose,	- 59.6 mg
carboxymethyl starch sodium (sodium starch glycolate),	- 38 mg
sodium lauryl sulfate,	- 10 mg
povidone,	- 10 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

Description:

Capsules №1 with a case and a lid of blue color.

Contents of capsules: granules of white or almost white color.

Pharmacotherapeutic group:Lipase GIT inhibitor

ATX: & nbsp

A.08.A.B.01 Orlistat

Pharmacodynamics:

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 a day), it inhibits about 30% the intake of fat from the diet by about 30%.

Pharmacokinetics:

Absorption is low; 8 hours after ingestion unchanged orlistat in plasma is not determined (concentration below 5 ng / ml).

The systemic exposure of orlistat is minimal. After ingestion of 360 mg radioactively labeled ¹⁴C-orlistat peak of radioactivity in plasma was reached after about 8 hours; the concentration of unchanged orlistat was close to the detection limit (less than 5 ng / ml). In therapeutic studies, including monitoring of plasma samples of patients, unchanged orlistat was determined sporadically in the 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% associated with plasma proteins, mainly with lipoproteins and albumin. Orlistat minimally penetrates into the red blood cells. Metabolized mainly in the gastrointestinal wall with the formation of pharmacologically inactive metabolites M1 (hydrolyzed four-membered lactone ring) and M3 (M1 with the cleaved N-formylleucine residue). In a study in obese patients receiving 14C-orlistat, 2 metabolites, M1 and M3, accounted for about 42% of the total radioactivity of the plasma. M1 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).Given the low activity and low concentration of metabolites in plasma (about 26 ng / ml and 108 ng / ml for M1 and M3 respectively 2-4 hours after taking orlistat at therapeutic doses), these metabolites are considered pharmacologically insignificant. The main metabolite M1 has a short T1 / 2 (about 3 hours), the second metabolite is displayed more slowly (T1 / 2 - 13.5 hours). In patients with obesity, Css metabolite M1 (but not M3) increases in proportion to the dose of orlistat. After a single oral intake of 360 mg of 14C-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 M1 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 14C-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 limited data, T1 / 2 of absorbed orlistat fluctuates within 1-2 hours.

Indications:

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

- Reducing the risk of repeated weight gain after its initial decline.

Orlistat is indicated in obese patients with a body mass index (BMI) ≥30 kg / m2 or ≥28 kg / m2 in the presence of other risk factors (diabetes, hypertension, dyslipidemia). (Calculation of BMI: BMI = M / P2, where M - body weight, kg, P - height, m)

Contraindications:

- hypersensitivity to orlistat or other components of the drug;

- malabsorption syndrome;

- cholestasis;

- simultaneous administration with cyclosporine;

- Pregnancy and lactation;

- age to 18 years.

Carefully:

The presence of hyperoxaluria in history, nephrolithiasis (calcium oxalate stones).

Pregnancy and lactation:Orlistat it 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 the orlistat in breast milk, in connection with which the use of the drug Orlistat in the period of breastfeeding is not recommended.

Dosing and Administration:

Inside, 120 mg (1 caps.) 3 times a day during each meal or no later than 1 hour after a meal (if the food does not contain fat, then you can skip the reception).

Side effects:

The incidence of adverse reactions listed below was determined according to the following: very often (> 1/10); often (> 1/100, <1/10); sometimes (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), 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, imperative 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 in the 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 lesion.

On the part of the respiratory system, chest and mediastinal organs: very often - infections of the upper respiratory tract, often - infections 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 indicated in the instruction are aggravated or any other side effects not indicated in the instructions are noted, you should inform the doctor about it.

Overdose:

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 a 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 detected, the patient should be monitored for 24 hours. According to studies in animals and humans, systemic effects associated with lipase inhibitory properties of orlistat should be rapidly reversible.

Interaction:

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 simultaneous application of orlistat and cyclosporine, the plasma level in the plasma decreases (orlistat and ciclosporin should not be taken simultaneously; to reduce the likelihood of drug interactions ciclosporin should be taken 2 hours before or 2 hours after taking orlistat).

With the simultaneous use of warfarin or other indirect anticoagulants with orlistatom, the level of prothrombin can decrease and the value of the INR index may change, therefore, INR 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 about 60%.

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

At simultaneous reception with orlistatom the absorption of vitamins A, D, E and K is reduced. If recommended multivitamins, they should be taken at least 2 hours after taking the drug Orlistat or before bedtime.

Reducing body weight can improve metabolism in diabetic patients, so 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, losartan, glibenclamide, oral contraceptives, nifedipine, furosemide, captopril, atenolol and ethanol were not noted.

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.

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. Because the orlistat reduces the absorption of some fat-soluble vitamins, to ensure their adequate intake into the body, patients should take multivitamin preparations containing fat-soluble vitamins. 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. 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.Since absorption of vitamin K with orlistat may decrease, in patients receiving orlistat on the background of long-term continuous intake of warfarin, blood coagulation parameters should be monitored.

The intake of orlistat at doses exceeding 120 mg 3 times a 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 some patients, the content of oxalate in urine may increase with orlistat. As with other medications to reduce body weight, in some patient groups (for example, with anorexia nervosa or bulimia), there is a possibility of abuse of orlistat.

Orlistat's induction of weight loss may 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 derivatives) or insulin. If, after 12 weeks of therapy with the drug Orlistat a decrease in body weight was less than 5% of the original, it is necessary to consult a doctor to decide whether to continue treatment with orlistat.
Treatment should not last more than 2 years.

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

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

Does not affect the ability to drive vehicles and service moving machinery.

Form release / dosage:Capsules 120 mg.

Packaging:By 7 or 21 caps. in a planar cell box made of PVC film and foil of aluminum printed lacquered.

By 1, 2, 3, 4, 6, 12 contour mesh packages are placed in a pack of cardboard.

Storage conditions:In dry, dark place at a temperature of not more than 25 ^aboutFROM.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001275

Date of registration:24.11.2011

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

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp20.11.2015

Illustrated instructions

Instructions

Orlistat (Orlistat)