Pharmacy No. 84. Delivery of medicines to your home and office.

Medicines

my basket

Apteka84.kz is an online pharmacy that offers its customers medicines, medicinal and decorative cosmetics, dietary supplements, vitamins, baby food, intimate products for adults, medical equipment and thousands of other medical and cosmetic products at low prices. All data presented on the Apteka84.kz website is for informational purposes only and is not a substitute for professional medical care. Apteka84.kz strongly recommends that you carefully read the instructions for use contained in each package of medicines and other products. If you currently have any symptoms of the disease, you should seek help from a doctor. You should always tell your doctor or pharmacist about all the medicines you take. If you feel you need further help, please consult your local pharmacist or contact our GP online or by telephone.

Instructions for use ORSOTEN

Suction

Studies involving normal weight and obese volunteers showed that the extent of orlistat absorption was minimal. 8 hours after oral administration, the concentration of unchanged orlistat in the blood plasma was practically undetectable (less than 5 ng/ml). After administration in therapeutic doses, detection of unchanged orlistat occurred only in rare cases, and its concentrations were extremely low (<10 ng/ml or 0.02 mmol). There are no signs of accumulation, which confirms minimal absorption of the drug.

Distribution

Vd cannot be determined because drug absorption is minimal and there is no detectable systemic pharmacokinetics. In vitro, orlistat is more than 99% bound to plasma proteins (mainly lipoproteins and albumin). Orlistat can penetrate red blood cells in minimal quantities.

Metabolism

Based on animal studies, orlistat is metabolized primarily in the intestinal wall. Based on a study involving obese patients, it was established that from the minimum fraction of the drug dose that undergoes systemic absorption, 2 main metabolites - M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with a cleaved N-formylleucine residue) - account for approximately 42% of the total plasma concentrations.

M1 and M3 have an open beta-lactone ring and extremely weak lipase inhibitory activity (1000 and 2500 times weaker than orlistat, respectively).

Given this low inhibitory activity and low plasma concentrations after therapeutic doses (average 26 ng/ml and 108 ng/ml, respectively), these metabolites are considered pharmacologically inactive.

Removal

Studies involving normal weight and obese patients have shown that the main route of elimination of unabsorbed drug is excretion in the feces. About 97% of the administered dose of the drug was excreted in the feces, of which 87% was orlistat in unchanged form.

The cumulative excretion through the kidneys of all substances structurally related to orlistat is less than 2% of the dose taken. The time for complete elimination of the drug from the body (with feces and urine) is 3-5 days. The ratio of excretion routes in volunteers with normal body weight and obesity turned out to be the same. Orlistat, M1 and M3 can be excreted in the bile.

Orsoten 120 mg 21 pcs. capsules

pharmachologic effect

Inhibiting gastrointestinal lipases.

Composition and release form Orsoten 120 mg 21 pcs. capsules

Capsules - 1 capsule:

active substance: orsoten semi-finished granules - 225.6 mg (in terms of the active substance orlistat - 120 mg);
excipients: MCC;
capsule: body (titanium dioxide (E171), hypromellose); cap (titanium dioxide (E171), hypromellose).

Capsules 120 mg. 7 caps. in blister packs made of combined material OPA/aluminum/PVC and aluminum foil or 21 capsules. in blister packs made of combined PVC/PVDC material and aluminum foil.

3, 6 or 12 blister packs (7 caps each) or 1, 2 or 4 blister packs (21 caps each) are placed in a cardboard pack.

Description of the dosage form

Hypromellose capsules.

The cap and body of the capsule are white to white with a yellowish tint.

The contents of the capsules are microgranules or a mixture of powder and microgranules of white or almost white color. The presence of compacted agglomerates that easily crumble when pressed is allowed.

Directions for use and doses

Inside.

Long-term therapy of obese or overweight patients with risk factors associated with obesity, in combination with a moderately hypocaloric diet. In adults and children over 12 years of age, the recommended dose of orlistat is 1 caps. 120 mg with each main meal (immediately before, during, or no later than 1 hour after a meal).

In combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and/or insulin) and/or a moderately hypocaloric diet in patients with type 2 diabetes mellitus who are overweight or obese. In adults, the recommended dose of orlistat is 1 capsule. 120 mg with each main meal (immediately before, during, or no later than 1 hour after a meal).

If meals are skipped or the food does not contain fat, Orsoten® can also be skipped.

Orsoten® should be taken in combination with a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fat. The daily intake of fats, carbohydrates and proteins must be divided into 3 main meals.

Increasing the dose of orlistat above the recommended one (120 mg 3 times a day) does not lead to an increase in its therapeutic effect.

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

Pharmacodynamics

The drug Orsoten® is a powerful, specific and reversible inhibitor of gastrointestinal lipases with a long-lasting effect. Its therapeutic effect occurs in the lumen of the stomach and small intestine and consists of the formation of a covalent bond with the active serine site of gastric and pancreatic lipases. The inactivated enzyme then loses the ability to break down food fats, which come in the form of triglycerides, into absorbable free fatty acids and monoglycerides. Since unsplit triglycerides are not absorbed, the resulting decrease in caloric intake into the body leads to a decrease in body weight. Thus, the therapeutic effect of the drug is carried out without absorption into the systemic circulation.

Based on fecal fat results, the effects of orlistat begin 24 to 48 hours after dosing. After discontinuation of orlistat, fecal fat content usually returns to pre-therapy levels within 48–72 hours.

Efficiency

Obese patients. In clinical studies, patients taking orlistat experienced greater weight loss compared to patients on diet therapy. Body weight loss began within the first 2 weeks after the start of treatment and lasted from 6 to 12 months, even in patients with a negative response to diet therapy. Over the course of 2 years, there was a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, compared to placebo, there was a significant reduction in body fat. Orlistat is effective in preventing weight gain. Re-gain of body weight, no more than 25% of what was lost, was observed in approximately half of the patients, and in half of these patients, no re-gain of body weight was observed or even a further decrease was observed.

Obese patients with type 2 diabetes: In clinical studies of 6 months to 1 year, overweight or obese patients with type 2 diabetes treated with orlistat experienced greater weight loss compared with patients treated with diet therapy alone . Body weight loss occurred mainly due to a decrease in the amount of fat in the body. It should be noted that before the start of the study, despite taking hypoglycemic agents, patients often had insufficient glycemic control. However, with orlistat therapy, a statistically and clinically significant improvement in glycemic control was observed. In addition, during orlistat therapy, a decrease in doses of hypoglycemic agents, plasma insulin concentrations, and a decrease in insulin resistance were observed.

Reducing the risk of developing type 2 diabetes in obese patients. In a 4-year clinical trial, orlistat was shown to significantly reduce the risk of developing type 2 diabetes (by approximately 37% compared to placebo). The degree of risk reduction was even greater in patients with baseline impaired glucose tolerance (approximately 45%). There was greater weight loss in the orlistat treatment group compared to the placebo group. Maintaining body weight at a new level was observed throughout the entire study period. Moreover, compared with placebo, patients treated with orlistat showed a significant improvement in their metabolic risk factor profile.

Pubertal obesity. In a 1-year clinical trial in obese adolescents taking orlistat, a decrease in BMI was observed compared with the placebo group, where there was even an increase in BMI. In addition, patients in the orlistat group showed a decrease in fat mass, as well as waist and hip circumferences compared to the placebo group. Also, patients receiving orlistat therapy experienced a significant decrease in dBP compared to the placebo group.

Pharmacokinetics

Suction. In volunteers with normal body weight and obesity, systemic exposure to the drug is minimal. Following a single oral dose of 360 mg orlistat, no unchanged orlistat could be detected in plasma, meaning that its concentrations were below 5 ng/mL. In general, after taking therapeutic doses, it was possible to detect unchanged orlistat in the blood plasma only in rare cases, and its concentrations were extremely low (

Distribution. Vd cannot be determined because Orsoten® is very poorly absorbed. Under in vitro conditions, orlistat is more than 99% bound to plasma proteins (mainly lipoproteins and albumin). In minimal quantities, orlistat can penetrate red blood cells.

Metabolism. Judging by the data obtained in animal experiments, orlistat metabolism occurs mainly in the intestinal wall. In a study in obese individuals, it was found that approximately 42% of the minimal fraction of orlistat that is subject to systemic absorption is accounted for by 2 main metabolites - M1 (four-membered hydrolyzed lactone ring) and M3 (M1 with a cleaved N-formylleucine residue).

Molecules M1 and M3 have an open β-lactone ring and inhibit lipase extremely weakly (1000 and 2500 times weaker than orlistat, respectively). Given this low inhibitory activity and low plasma concentrations (average 26 and 108 ng/ml, respectively) after taking therapeutic doses, these metabolites are considered pharmacologically inactive.

Excretion. Studies in normal and overweight individuals have shown that the main route of elimination is excretion of unabsorbed orlistat through the intestines. About 97% of the administered dose of the drug was excreted through the intestines, with 83% in the form of unchanged orlistat. The cumulative renal excretion of all substances structurally related to orlistat is less than 2% of the administered dose. The time until orlistat is completely eliminated from the body (through the intestines and kidneys) is 3–5 days. The ratio of orlistat elimination routes in volunteers with normal and overweight was the same. Both orlistat and the metabolites M1 and M3 can be excreted in the bile.

Pharmacokinetics in special clinical groups

Plasma concentrations of orlistat and its metabolites (M1 and M3) in children do not differ from those in adults when comparing the same doses of orlistat. Daily fecal fat excretion was 27% of dietary intake with orlistat and 7% with placebo.

Preclinical safety data

Based on preclinical data, no additional risks to patients were identified regarding the safety profile, toxicity, genotoxicity, carcinogenicity and reproductive toxicity. Animal studies also did not reveal a teratogenic effect. Due to the lack of a teratogenic effect in animals, it is unlikely to be detected in humans.

Indications for use Orsoten 120 mg 21 pcs. capsules

long-term therapy of obese patients (BMI ≥30 kg/m2) or overweight patients (BMI ≥28 kg/m2) with risk factors associated with obesity, in combination with a moderately hypocaloric diet;
in combination with hypoglycemic drugs (metformin, sulfonylureas and/or insulin) and/or a moderately hypocaloric diet in patients with type 2 diabetes mellitus who are overweight or obese.

Contraindications

hypersensitivity to the drug or any other components contained in the capsule;
chronic malabsorption syndrome;
cholestasis;
pregnancy;
breastfeeding period;
children's age up to 12 years.

With caution: concomitant therapy with cyclosporine; concomitant therapy with warfarin or other oral anticoagulants.

Application of Orsoten 120 mg 21 pcs. capsules during pregnancy and breastfeeding

No teratogenic or embryotoxic effects of orlistat were observed in animal reproductive toxicity studies. In the absence of a teratogenic effect in animals, a similar effect in humans should not be expected. However, due to the lack of clinical data, Orsoten® should not be prescribed to pregnant women.

It is unknown whether orlistat passes into breast milk, so its use during breastfeeding is contraindicated.

special instructions

The use of Orsoten® should be discontinued if, after 12 weeks of therapy, body weight has decreased by less than 5% compared to the initial body weight.

Clinical studies have found less weight loss in patients with type 2 diabetes mellitus receiving orlistat compared to patients without diabetes mellitus receiving orlistat.

The drug Orsoten® is effective in terms of long-term control of body weight (loss of body weight and its maintenance at a new level, prevention of re-gain of body weight). Treatment with Orsoten® leads to an improvement in the profile of risk factors and diseases associated with obesity, including hypercholesterolemia, type 2 diabetes mellitus, impaired glucose tolerance, hyperinsulinemia, arterial hypertension, and a decrease in the amount of visceral fat. When used in combination with hypoglycemic drugs such as metformin, sulfonylurea derivatives and/or insulin, in patients with type 2 diabetes mellitus who are overweight (BMI ≥28 kg/m2) or obese (BMI ≥30 kg/m2), Orsoten ® in combination with a moderately hypocaloric diet provides an additional improvement in the compensation of carbohydrate metabolism.

In clinical studies, the majority of patients had concentrations of vitamins A, D, E, K and beta-carotene within the normal range during 4 years of orlistat therapy.

A multivitamin may be prescribed to ensure adequate intake of all nutrients.

The patient should receive a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fat. A diet rich in fruits and vegetables is recommended. The daily intake of fats, carbohydrates and proteins must be divided into 3 main meals.

Cases of rectal bleeding have been observed with the use of orlistat. If severe and/or persistent bleeding symptoms occur, additional testing should be performed.

The likelihood of adverse reactions from the gastrointestinal tract may increase if Orsoten® is taken on a diet rich in fat (for example, 2000 kcal/day, of which more than 30% in the form of fat, which equals approximately 67 g of fat). Daily fat intake should be divided into 3 main meals. If Orsoten® is taken with foods very rich in fat, the likelihood of gastrointestinal reactions increases.

In patients with type 2 diabetes mellitus, a decrease in body weight during treatment with Orsoten® is accompanied by an improvement in the compensation of carbohydrate metabolism, which may allow or require a reduction in the dose of hypoglycemic drugs (for example, sulfonylurea derivatives).

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

If severe diarrhea develops while using orlistat, women using oral contraceptives should use additional contraceptive measures.

Rare cases of hypothyroidism and/or loss of hypothyroidism control have been reported with the use of orlistat. The mechanism of development of this phenomenon is unknown, but may be due to decreased absorption of iodized salt and/or levothyroxine sodium.

Orlistat has the potential to reduce the absorption of antiretroviral drugs for the treatment of HIV and the effectiveness of antiretroviral therapy. Before initiating orlistat therapy, the benefit/risk ratio should be carefully assessed in such patients.

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

Impact on the ability to perform potentially hazardous activities that require special attention and quick reactions (for example, driving, working with moving mechanisms). The drug Orsoten® does not affect the ability to drive vehicles and machines.

Overdose

In clinical studies in individuals with normal body weight and obese patients, single doses of 800 mg or repeated doses of orlistat 400 mg 3 times a day for 15 days were not accompanied by the occurrence of significant adverse events. In addition, obese patients have experience using orlistat 240 mg 3 times a day for 6 months, which was not accompanied by a significant increase in the incidence of adverse events.

Symptoms: Either no adverse events were reported, or adverse events did not differ from those observed when taking orlistat in therapeutic doses.

Treatment: It is recommended to observe the patient for 24 hours. According to studies in humans and animals, any systemic effects that could be associated with the lipase inhibitory properties of orlistat should be quickly reversible.

Side effects Orsoten 120 mg 21 pcs. capsules

Classification of the frequency of side effects, recommended by WHO: very often - ≥1/10; often - from ≥1/100 to

Clinical trial data

Adverse reactions to orlistat occurred mainly from the gastrointestinal tract and were due to the pharmacological effect of the drug, which interferes with the absorption of dietary fats. The incidence of adverse events decreased with long-term use of orlistat.

The following adverse events occurred with an incidence of >2% and an incidence of ≥1% compared with placebo.

Infectious and parasitic diseases: very often - influenza.

From the side of metabolism: very often - hypoglycemia*.

Mental disorders: often - anxiety.

From the nervous system: very often - headache.

From the respiratory system, chest and mediastinal organs: very often - upper respiratory tract infections; often - lower respiratory tract infections.

From the gastrointestinal tract: very often - pain or discomfort in the abdomen, oily discharge from the rectum, release of gases with some discharge, imperative urge to defecate, steatorrhea, flatulence, loose stools, increased frequency of bowel movements; often - pain or discomfort in the rectum, soft stools, fecal incontinence, dental damage, gum damage, bloating*.

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

On the part of the genital organs and breast: often - irregular menstruation.

General disorders and disorders at the injection site: often - weakness.

In patients with type 2 diabetes mellitus, the nature and frequency of adverse events were comparable to those in overweight and obese individuals without diabetes mellitus.

The incidence of gastrointestinal disorders increases with increasing fat content in the diet. Patients should be informed of the possibility of gastrointestinal adverse reactions and taught how to manage them through better diet, especially regarding the amount of fat contained in the diet. Adopting a low-fat diet reduces the likelihood of gastrointestinal side effects and thereby helps patients control and regulate their fat intake.

As a rule, these adverse reactions were mild and transient. They occurred in the early stages of treatment (in the first 3 months), and most patients had no more than one episode of such reactions.

In the 4-year clinical study, the overall safety profile did not differ from that obtained in the 1- and 2-year studies. At the same time, the overall incidence of adverse events from the gastrointestinal tract decreased annually over the 4-year period of taking orlistat.

Post-marketing surveillance

The adverse events listed below were identified in spontaneous post-marketing reports, the frequency of development is unknown.

From the immune system: hypersensitivity reactions, the main clinical symptoms of which were itching, skin rash, urticaria, angioedema, bronchospasm and anaphylaxis.

From the digestive system: rectal bleeding, diverticulitis, pancreatitis.

From the liver and biliary tract: cholelithiasis, isolated, possibly serious cases of liver damage leading to liver transplantation or death.

From the skin and subcutaneous tissues: bullous rash.

From the kidneys and urinary tract: oxalate nephropathy, which can sometimes lead to the development of renal failure.

Laboratory data: increased activity of liver transaminases and alkaline phosphatase, decreased concentration of prothrombin in the blood plasma, increased INR values and cases of unbalanced anticoagulant therapy, which led to changes in hemostatic parameters. Cases of hyperoxaluria have been reported.

From the musculoskeletal system and connective tissue: cases of seizures have been observed with the simultaneous use of orlistat and antiepileptic drugs.

Drug interactions

With simultaneous use of orlistat and cyclosporine, a decrease in the concentration of cyclosporine in the blood plasma was observed, which may lead to a decrease in the immunosuppressive effectiveness of cyclosporine. Therefore, concomitant use of orlistat and cyclosporine is not recommended. However, if such concomitant use is necessary, more frequent monitoring of cyclosporine plasma concentrations is recommended, both when used simultaneously with orlistat and after discontinuation of orlistat. The concentration of cyclosporine in the blood plasma should be monitored until it stabilizes.

When used simultaneously with Orsoten®, a decrease in the absorption of vitamins D, E and beta-carotene was observed. If multivitamins are recommended, they should be taken at least 2 hours after taking Orsoten® or before bedtime.

When amiodarone was used orally during orlistat therapy, a decrease in the systemic exposure of amiodarone and desethylamiodarone was observed (by 25–30%), however, due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is unclear. The addition of Orsoten® to long-term amiodarone therapy may result in a decrease in the therapeutic effect of amiodarone (no studies have been conducted).

The simultaneous use of Orsoten® and acarbose should be avoided due to the lack of data from pharmacokinetic studies.

Cases of seizures have been observed when taking orlistat and antiepileptic drugs simultaneously. A cause-and-effect relationship between the development of seizures and orlistat therapy has not been established. However, patients should be monitored for possible changes in seizure frequency and/or severity. According to clinical studies, there is no interaction of orlistat with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, nifedipine GITS (gastrointestinal therapeutic system) and nifedipine with slow release, sibutramine or ethanol.

However, with the simultaneous use of orlistat and warfarin or other anticoagulants, a decrease in prothrombin concentration and an increase in INR may be observed, which can lead to changes in hemostatic parameters. It is necessary to monitor the INR during concomitant therapy with warfarin or other oral anticoagulants.

Rare cases of hypothyroidism and/or loss of control have been reported. The mechanism of development of this phenomenon is unknown, but may be due to decreased absorption of iodized salt and/or levothyroxine sodium.

There have been cases of decreased effectiveness of antiretroviral drugs for the treatment of HIV, antidepressants and antipsychotics (including lithium preparations), coinciding with the initiation of orlistat in previously compensated patients. Orlistat therapy should only be initiated after careful evaluation of its possible effects in such patients.

Orlistat can indirectly reduce the effectiveness of oral contraceptives, which in some cases can lead to unplanned pregnancy. It is recommended to use an additional method of contraception also in case of severe diarrhea.