Orlixen 120 - instructions for use, dose, side effects, contraindications

Auxiliary substances of the substance-pellet: cellulose microcrystalline - 98.64 mg, sodium carboxymethyl starch - 10.08 mg, sodium lauryl sulfate - 6.24 mg, povidone - K30 - 5.04 mg.

Hard gelatin capsules № 0

Capsule body composition: dye blue patented - 0.2786%, titanium dioxide 2.0%, gelatin up to 100%.

Composition of cap capsule: dye blue patented - 0.2786%, titanium dioxide 2.0%, gelatin up to 100%.

Description:

Hard gelatin capsules number 0. The capsule body and capsule are blue, opaque.

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

Pharmacotherapeutic group:Lipase GIT inhibitor

ATX: & nbsp

A.08.A.B.01 Orlistat

Pharmacodynamics:

The active substance of the drug Orlixen 120 - orlistat - is a potent, specific and reversible inhibitor of gastrointestinal lipases, which has a prolonged action. Its therapeutic effect is carried out in the lumen of the stomach and small intestine and consists in the formation of a covalent bond with the active serine portion of the gastric and pancreatic lipases. The inactivated enzyme loses its ability to break down the food fats that come in the form of triglycerides, to sucking free fatty acids and monoglycerides.Since uncleaved triglycerides are not absorbed, the resulting decrease in the intake of calories into the body leads to a decrease in body weight. Thus, the therapeutic effect of orlistat is carried out without absorption into the systemic bloodstream.

Judging by the results of the fat content in the feces, the effect of orlistat begins 24-48 hours after ingestion. After cancellation of orlistat, the fat content in the stool after 48-72 h 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. 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, a decrease in the dose of hypoglycemic agents, insulin concentration, and a decrease in insulin resistance were observed.

Reducing the risk of developing type 2 diabetes in obese patients in a four-year clinical trial showed 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.

Obesity in puberty children

In a 1-year clinical trial in adolescents with obesity, orlistat, a decrease in the body mass index (BMI) was observed compared with the placebo group, where there was even an increase in BMI. In addition, patients in the orlistat group had a reduction in fat mass, as well as waist and hip circumference 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

In volunteers with normal body weight and obesity, the systemic effect of orlistat is minimal. After a single oral intake of the drug in a dose of 360 mg unchanged orlistat in plasma is not determined, which means that its concentrations are below 5 ng / ml. In general, after taking therapeutic doses, identify unchanged orlistat In plasma it was possible only in rare cases, while its concentrations were extremely small (<10 ng / ml or 0.02 μmol). Signs of cumulation are absent, which confirms that the absorption of orlistat is minimal.

Distribution

The volume of distribution can not be determined, because orlistat is practically not absorbed and does not have established systemic pharmacokinetics. In vitro orlistat more than 99% associated with blood plasma proteins (mainly with lipoproteins and albumin). In minimum quantities orlistat can penetrate into erythrocytes.

Metabolism

Judging from the data obtained in the experiment on animals, the metabolism of orlistat occurs mainly in the intestinal wall.In a study in obese individuals found that approximately 42% of the minimum fraction of orlistat that undergoes systemic absorption accounts for two major metabolites - M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with a split residue N-formleleucine). Molecules M1 and M3 have an open β-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

Studies in individuals with normal and overweight showed that the main way to eliminate unsweetened orlistat is to withdraw through the intestine - about 97% of the dose taken, with 83% in the form of unchanged orlistat.

The cumulative excretion of all substances structurally related to orlistat by the kidneys is less than 2% of the dose taken. Time until the complete excretion of orlistat from the body (through the intestine and kidneys) is 3-5 days. The ratio of pathways for orlistat in volunteers with normal and overweight is the same.

Pharmacokinetics in special clinical groups

Concentrations of orlistat and its metabolites (M1 and M3) in blood plasma in children do not differ from those in adults when comparing identical doses of the drug. Daily removal of fat through the intestine is 27% of the intake with food when using orlistat and 7% - with a placebo.

Indications:

Long-term therapy of patients with obesity (BMI ≥30 kg / m²) or patients with excessive body weight (BMI> 28 kg / m²), who are associated with obesity risk factors, in combination with a moderately hypocaloric diet.

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

Contraindications:

- Hypersensitivity to orlistat or any of the components of the drug;

- syndrome of chronic malabsorption;

- cholestasis;

- period of pregnancy and breastfeeding;

- children under 12 years.

Carefully:

Simultaneous use with cyclosporine, warfarin or other oral anticoagulants, age to 18 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, orlistat contraindicated in pregnancy.

Since it is not known whether the orlistat in breast milk, its use is contraindicated in the period of breastfeeding.

Dosing and Administration:

Long-term therapy of patients with obesity or overweight patients, 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 Orlixen 120 is one 120 mg capsule with each main meal (during meals or not later than 1 hour after eating), with water.

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:

in adults The recommended dose of Orlixen 120 is one 120 mg capsule with each main meal (during meals or not later than 1 hour after eating), with water.

If food intake is missed or if the food does not contain fat, then the drug intake can also be skipped.

Orixen 120 should be taken in combination with a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fats. The succinic intake of fats, carbohydrates and proteins must be divided into three main methods.

An increase in the dose of the drug over the recommended dose (120 mg 3 times a day) does not lead to an increase in its therapeutic effect.

Use in special patient groups

The efficacy and safety of orlistat in patients with impaired hepatic and / or renal function, as well as in patients of elderly and children (under 12 years of age) have not been studied.

Side effects:

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

Infectious and parasitic diseases: Often - flu.

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

Disorders of the psyche: often - anxiety.

Impaired nervous system: Often - headache.

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

Disorders from the gastrointestinal tract: very often - oily discharge from the rectum, the withdrawal of gases with a certain amount of detachable, mandatory urges for defecation, steatorrhoea, frequent bowel movements, loose stools, flatulence, pain and 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 and discomfort in the rectum, fecal incontinence, tooth damage, gum lesion.

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

Violations of the genitals and mammary gland: often - irregular menstruation.

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

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 four-year clinical study, the overall safety profile did not differ from that obtained in one- and two-year studies. The overall incidence of adverse events from the gastrointestinal tract decreased annually during the four-year period of orlistat administration.

Postmarketing surveillance

The undesirable phenomena listed below were detected with spontaneous post-registration messages, the frequency is unknown.

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

Disorders from the gastrointestinal tract: rectal bleeding, diverticulitis, pancreatitis.

Disturbances from the liver and bile ducts: cholelithiasis, cases of liver damage leading to its transplantation or lethal outcome.

Disturbances from the skin and subcutaneous tissues: Bullous rash.

Disorders from the kidneys and urinary tract: hyperoxaluria; oxalate nephropathy, which can sometimes lead to the development of renal failure.

Laboratory data: very rarely - increased activity of transaminases and alkaline phosphatase; decreased prothrombin; an increase in the international normalized relationship (INR) with simultaneous use with anticoagulants.

Overdose:

In clinical studies in individuals with normal body weight and obesity, taking orlistat once in a dose of 800 mg or repeated taking orlistat 400 mg 3 times a day for 15 days was not accompanied by the development of significant adverse events. In addition, in patients with obesity, orlistat at a dose of 240 mg 3 times a day for 6 months was not accompanied by a significant increase in the incidence of adverse events.

In cases of overdose orlistat reported either the absence of adverse effects or adverse events did not differ from those observed when receiving oristata in therapeutic doses.

In case of significant overdosing recommended observation of the patient within 24 hours. According to preclinical and clinical studies, systemic effects associated with orlistat lipazingibiruyuschimi properties must be rapidly reversible.

Interaction:

There were no interaction with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, phentermine, pravastatin, nifedipine GITS (gastro-intestinal therapeutic system) and nifedipine slow release, sibutramine or ethanol (based on the studies of interactions between drugs ).

At the same time taking orlistat and warfarin or other oral anticoagulants may experience a decrease in the concentration of prothrombin time and INR increase, resulting in a change of haemostatic parameters, so you need to monitor the performance of INR during concomitant treatment with warfarin or other oral anticoagulants.

At simultaneous reception with orlistatom there was a decrease in absorption of fat-soluble vitamins D, E and beta-carotene. If recommended multivitamins, they should be taken at least 2 hours after taking the drug or before bedtime.

With the simultaneous administration of orlistat and cyclosporine, a decrease in the concentration of cyclosporine in the blood plasma was noted, therefore, when cyclosporine and orlistat are taken simultaneously, a more frequent determination of the concentration of cyclosporine in the blood plasma is recommended.

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. Adding orlistat to prolonged therapy with amiodarone may lead to a decrease in the therapeutic effect of amiodarone (no studies have been performed).

It is necessary to avoid the simultaneous administration of orlistat and acarbose due to the lack of pharmacokinetic data.

With the simultaneous administration of orlistat and antiepileptic drugs, cases of seizures developed.Causal relationship between the development of seizures and orlistat therapy is not established. Nevertheless, patients should be monitored for possible changes in the frequency and / or severity of the seizure syndrome.

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 have been cases of a decrease in the effectiveness of antiretroviral drugs for the treatment of HIV (human immunodeficiency virus), antidepressants and antipsychotics (including lithium preparations) that coincide with the onset of orlistat in previously compensated patients.

Special instructions:

Orlixen 120 should be discontinued if, after 12 weeks of therapy, body weight decreased by less than 5% compared to the initial body weight.

Clinical studies have revealed less weight loss in patients with type 2 diabetes who are receiving orlistat, in comparison with patients without diabetes mellitus, receiving orlistat.

The drug Orlixen 120 is effective in terms of long-term control of body weight (weight loss, maintaining it at an appropriate level and preventing repeated body weight gain).

Treatment with the drug 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 with excess body weight (BMI) ≥28 kg / m²) or obesity (BMI ≥ 30 kg / m²), the drug in combination with a moderately hypocaloric diet provides an additional improvement in the compensation of carbohydrate metabolism.

In clinical studies, in most patients, concentrations of vitamins A, D, E, K and beta-carotene during 4 years of 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 hypocaloric diet containing no more than 30% of calories in the form of fats. We recommend eating rich in fruits and vegetables. Daily intake of fats, carbohydrates and proteins must be divided into 3 main methods. The likelihood of adverse reactions from the gastrointestinal tract may increase if the drug is taken amid a diet rich in fats (for example, 2000 kcal / day, of which more than 30% is fat, which is about 67 g of fat).

In patients with type 2 diabetes mellitus, a decrease in body weight when treated with the drug is accompanied by an improvement in the compensation of carbohydrate metabolism, which may or may require a reduction in the dose of hypoglycemic drugs (eg, sulfonylurea derivatives).

When orlistat was used, cases of rectal bleeding were observed. If severe and / or persistent bleeding symptoms occur, additional testing is necessary.

It is necessary to monitor coagulation parameters (for example, MNO) with concomitant therapy with oral anticoagulants.

If severe diarrhea develops with orlistat, women who use oral contraceptives need to take additional contraceptive measures.

When Orlistat was used, rare cases of development of hypothyroidism and / or violation of its control were noted. The mechanism of development of this phenomenon is unknown, but it can be caused by a decrease in absorption of iodized salt and / or levothyroxine sodium.

Orlistat has the potential to reduce the absorption of antiretroviral drugs to treat HIV and to reduce the effectiveness of antiretroviral therapy. Before starting orlistat therapy, you should carefully evaluate the benefit / risk ratio in such patients.

When using orlistat, the development of oxalate nephropathy is possible, which can sometimes lead to the development of renal failure. An increased risk is noted in patients with chronic renal failure and / or dehydration.

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

No adverse effect of orlistat on the ability to drive vehicles and mechanisms has been identified.

Form release / dosage:

Capsules, 120 mg.

Packaging:

For 5, 10 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30, 40, 50, 100 or 120 capsules in cans of polyethylene terephthalate for medicinal products sealed with caps screwed on with first opening control or with a "push-turn" system made of polypropylene or polyethylene or polypropylene cans for drugs sealed with lids stretched with the control of the first opening of polyethylene or cans of polypropylene for drugs, sealed with lids pulled with the control of the first opening of high-pressure polyethylene.

One bank or 1, 2, 3, 4, 5, 6, 8, 9, 10 or 16 contour mesh packages together with the instruction for use are placed in a cardboard package.

It is allowed to bundle 2 or 3 cardboard packages (packs) into a group package (shipping container) from cardboard for consumer packaging.

Storage conditions:

In the dark 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003787

Date of registration:17.08.2016

Expiration Date:17.08.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp11.06.2017

Illustrated instructions

Instructions

Orlixen 120 (Orlixen 120)