Orlistat Canon - instructions for use, dose, side effects, contraindications

active substance: orlistat, substance-pellets 50% 240 mg, including: orlistat 120 mg,starch corn pellets 64.5 mg, macrogol (polyethylene glycol 6000) 4.13 mg, sodium lauryl sulfate 9.38 mg, povidone (Kollidon 30) 36.79 mg, polysorbate 80 (Tween 80) 2.06 mg, talc 3, 14 mg;

hard gelatin capsule number 1 76 mg, including: body - titanium dioxide 0.9244 mg, gelatin 45.2956 mg, cap - titanium dioxide 0.3971 mg, gelatin 29.1077 mg, dye quinoline yellow 0.2739 mg, dye sunset yellow 0.0013 mg.

Description:Hard gelatin capsules No. 1, white body, yellow lid. The contents of capsules are spherical granules with no visible defects of white or almost white color.

Pharmacotherapeutic group:Inhibitor of gastrointestinal tract lipases

ATX: & nbsp

A.08.A.B.01 Orlistat

Pharmacodynamics:Orlistat - a powerful, specific and reversible inhibitor of long-acting gastrointestinal lipases. It acts in the lumen of the stomach and small intestine, forming a covalent bond with the active serine portion of the gastric and pancreatic lipases. The inactivated enzyme is not able to break down the food fats that come in the form of triglycerides, to absorbed free fatty acids and monoglycerides. Undivided triglycerides are not absorbed, due to which, the intake of calories in the body decreases,which leads to a decrease in body weight. The therapeutic effect of the drug is carried out without absorption into the systemic bloodstream. Increases the concentration of fat in the stool after 24-48 hours after ingestion. Provides effective control of body weight, reduction of fat depot. After the drug is withdrawn, the fat content in the stool after 48-72 hours usually returns to the level that occurred before the start of therapy.

Efficiency.

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. Redrawing the body mass, not more than 25% of the lost,was observed in about half of the patients, and half of these patients did not observe recurrence of body weight or even noted its 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, 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 mellitus (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 a clinical study of 1 year duration in adolescents with obesity, with orlistat, a decrease in the body mass index was observed compared to the placebo group, where there was even an increase in the body mass index. In addition, patients of the orlistat group had a decrease in fat mass, as well as 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 is low. After 8 hours after ingestion of the therapeutic dose, the unchanged orlistat in blood plasma is practically not determined (concentration <5 ng / ml). Signs of cumulation are absent, which is consistent with the minimum absorption of the drug.

Distribution

The volume of distribution can not be established, since orlistat is practically not absorbed and does not have established systemic pharmacokinetics. Orlistat more than 99% associated with blood plasma proteins in vitro (mainly with lipoproteins and albumin). Orlistat in minimal amounts can penetrate into the red blood cells.

Metabolism

Metabolism of orlistat occurs mainly in the intestinal wall with the formation of pharmacologically inactive metabolites: M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with the cleaved residue of M-formylleucine). M1 and M3 molecules have an open beta-lactone ring and extremely weakly inhibit lipase (respectively, 1000 and 2500 times weaker than orlistat). Given such low inhibitory activity and low plasma concentrations (an average of 26 ng / ml and 108 ng / ml), respectively, after taking therapeutic doses, these metabolites are considered pharmacologically inactive.

Excretion

The main way of excretion through the intestine is about 97% of the dose, 83% of which is unchanged orlistat. Total excretion by the kidneys of all metabolites of orlistat is <2% of the accepted dose of orlistat. The time of complete excretion (through the intestines and kidneys) is 3-5 days. The ratio of pathways for orlistat in individuals with normal body weight and obesity was similar. Orlistat and metabolites can also be excreted with bile.

Pharmacokinetics of special groups of patients

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. Daily excretion of fat with feces is 27% of the intake with food with orlistat and 7% with placebo.

Indications:

- Long-term therapy of obese patients (body mass index ≥ 30 kg / m2) or overweight patients (body mass index> 28 kg / m2), including those associated with obesity risk factors, combined with a moderately hypocaloric diet.

- In complex therapy with hypoglycemic drugs (metformin, sulfonylureas and / or insulin derivatives) and / or a moderately low-calorie diet for patients with type 2 diabetes mellitus with overweight or obesity.

Contraindications:Hypersensitivity to orlistat or any other components of the drug; syndrome of chronic malabsorption; cholestasis; pregnancy; the period of breastfeeding; children under 12 years.

Pregnancy and lactation:

Preclinical studies did not reveal a teratogenic and embryotoxic effect of orlistat. However, due to the lack of clinical data on the use in pregnant women, the drug Orlistat Canon is contraindicated in pregnancy.

Due to the fact that there are no data on the penetration of orlistat into breast milk, the use of orlistat during breastfeeding is contraindicated.

Dosing and Administration:

Inside, washing with water, with each main meal, with food or not later than an hour after eating. If food intake is missed or food is fat-free, Orlistat can also be taken.

Long-term therapy of obese patients or patients with excessive body weight, including those associated with obesity risk factors, combined with a moderately hypocaloric diet:

in adults and children over 12 years of age the recommended dose of orlistat is one capsule of 120 mg.

In combination with hypoglycemic drugs (metformin, derivatives sulfonylureas and / or insulin) 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 one capsule of 120 mg. The dose of Orlistat Canon, which exceeds 120 mg 3 times a day, does not enhance its therapeutic effect.

If, after 12 weeks of taking the drug, a decrease in body weight does not occur (no more than 5% of the original body weight), the patient should consult a physician to determine whether further use is advisable.

The efficacy and safety of orlistat 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.

Side effects:

Adverse events with orlistat were noted mainly from the gastrointestinal tract (GIT) and were caused by an increase in the amount of fat in the feces. With prolonged therapy with orlistat, the incidence of adverse events decreases.

The following side effects are given in accordance with the WHO classification of the incidence of side effects:

Often - ≥ 1/10 appointments (> 10%)

often from ≥1 / 100 to <1/10 of appointments (> 1% and <10%)

infrequently - from ≥1 / 1000 to <1/100 of prescriptions (> 0.1% and <1%)

rarely from ≥1 / 10000 to <1/1000 assignments (> 0.01% and <0.1%)

very rarely - <1/10000 prescriptions (<0.01%)

frequency is not known - according to available data, it is not possible to establish the frequency of occurrence.

Disturbances from the nervous system

Often: headache.

Disorders of the psyche

Often: anxiety.

Disorders from the gastrointestinal tract

Often: pain / discomfort in the abdomen, oily discharge from the rectum, flatulence and the release of gases with a certain amount of detachable, imperative desires for defecation, steatorrhea, loose stool, increased frequency of defecation.

Often: a soft chair; pain or discomfort in the rectum, fecal incontinence, bloating, damage to teeth and gums.

Disturbances from the respiratory system

Often: infection of the upper respiratory tract, influenza.

Often: infections of the lower respiratory tract.

Disorders from the kidneys and urinary tract.

Often: urinary tract infections.

Violations of the genitals and mammary gland

Often: dysmenorrhea.

Disorders from the metabolism and nutrition.

Often: hypoglycemia (in patients with type 2 diabetes mellitus).

General disorders and disorders at the site of administration

Often: weakness.

Postmarketing observations

Violations of the blood and lymphatic system

Frequency not known: a decrease in prothrombin, an increase in INR (the international normalized ratio). These side effects were observed with the simultaneous use of orlistat and anticoagulants.

Disorders from the gastrointestinal tract

Rarely: increased activity of "liver" transaminases, alkaline phosphatase.

Frequency not known: rectal bleeding, diverticulitis, pancreatitis.

Disturbances from the liver and bile ducts

Rarely: increased activity of transaminases, hepatitis (a causal relationship with reception orlistat or pathophysiological mechanisms of development are not established).

Frequency not known: cholelithiasis.

Disorders from the rut and subcutaneous tissues

Rarely: bullous rash.

Disturbances from the musculoskeletal and connective tissues

Frequency not known: convulsions (were observed with simultaneous reception with antiepileptic drugs).

Disorders from the kidneys and urinary tract

Frequency not known: oxalate nephropathy.

Allergic reactions

Rarely: skin itching, rash, hives, angioedema, bronchospasm, anaphylaxis. 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 with 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.

Overdose:

In individuals with normal body weight and obese patients, taking single doses of 800 mg or repeatedly taking the drug 400 mg 3 times daily for 15 days 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 with orlistat, either the absence of undesirable events was reported, or the undesirable events did not differ from those observed when taking the drug in therapeutic doses.

In cases of severe overdose, it is recommended to observe the patient within 24 hours. According to studies in humans and animals, any systemic effects that could be associated with lipase inhibitory properties of orlistat should be rapidly reversible.

Interaction:

With the simultaneous use of orlistat and cyclosporine, a decrease in the concentration of cyclosporine in the blood plasma is possible, and therefore it is necessary to monitor the content of cyclosporine in the blood plasma.

With oral administration of amiodarone during therapy with orlistat, the systemic exposure of amiodarone and desethylamiodarone decreased by 25-30%, but due to the complicated pharmacokinetics of amiodarone, the clinical significance of this phenomenon is not clear.With the simultaneous use of orlistat with amiodarone, clinical monitoring and monitoring of ECG is recommended.

The drug interaction of orlistat with warfarin was not revealed, however, with the simultaneous administration of orlistat and warfarin or other anticoagulants, a decrease in the prothrombin concentration and an increase in INR may occur, which leads to a change in the haemostatic parameters.

Orlistat can reduce the absorption of fat-soluble vitamins A, D, E, K and beta-carotene. If the reception of multivitamins is indicated, they should be taken no earlier than 2 hours after taking orlistat or before bedtime.

Orlistat may reduce the absorption of antiepileptic drugs, which can lead to seizures.

Given the lack of studies of pharmacokinetic interaction, the co-administration of orlistat and acarbose should be avoided.

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

When taking with sodium levothyroxine concurrently, in connection with a decrease in absorption of inorganic iodine and / or levothyroxine sodium, hypothyroidism and / or a decrease in the control of hypothyroidism may develop.

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

Special instructions:

The drug Orlistat Canon is used for long-term monitoring of body weight (weight loss, maintaining it at an appropriate level and preventing the repeated addition of body weight).

Treatment with Orlistat Canon 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.

When used in combination with such hypoglycemic drugs as metformin, sulfonylureas and / or insulin derivatives in patients with type 2 diabetes mellitus with an overweight (body mass index (BMI) ≥ 28 kg / m²) or obesity (BMI ≥ 30 kg / m²), Orlistat Canon in combination with a moderately hypocaloric diet provides an additional improvement in the compensation of carbohydrate metabolism.

By reducing body weight against the background of taking Orlistat Canon, it is possible to improve carbohydrate metabolism in patients with type 2 diabetes, which can reduce the dose of hypoglycemic drugs.

In clinical studies in most patients, concentrations of vitamins A, D, E, K and betakaren for four years orlistat therapy remained within the norm. To ensure adequate supply of all nutrients, you can assign multivitamins.

The patient should be on a balanced moderately low-calorie diet. Diet and exercise are an important component of the program to reduce body weight. It is recommended to begin the diet program and physical exercises before the beginning of therapy with the drug. During the use of the drug, the patient should receive a moderately hypocaloric diet with a balanced nutrient content, in which approximately 30% is fat. Daily intake of fat should be distributed among the three main meals. It is recommended that food be rich in fruits and vegetables. The program of diet and exercise should be continued after,as the use of the drug will be discontinued.

A diet low in fat reduces the likelihood of developing unwanted effects from the gastrointestinal tract.

If symptoms such as weakness, fatigue, fever, jaundice and darkening of the urine occur, you should consult your doctor to rule out liver damage.

Effect on the ability to drive transp. cf. and fur:There was no adverse effect of Orlistat Canon on the ability to drive vehicles and mechanisms. 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:

By 7, 10 or 14 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 3, 6, 9, 12 contour cell packs of 7 or 10 capsules or 3, 6 contour packs of 14 capsules together with the instructions for use are placed in a pack of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002507

Date of registration:17.06.2014

Expiration Date:17.06.2019

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp11.06.2017

Illustrated instructions

Instructions

Orlistat Canon (Orlistat-Canon)