Expiration date: 08/20262

Active substance: Orlistat

Pharmacokinetics:

Suction. The absorption of orlistat low. After 8 hours after the ingestion of therapeutic doses of unmodified orlistat plasma practically determined (concentration - <5 ng / ml). Signs of cumulation are absent, confirming the minimum absorption of the drug.

Distribution. In vitro orlistat more than 99% bound to plasma proteins (mainly albumin and lipoproteins). The minimum amounts of orlistat can penetrate into erythrocytes.

Metabolism. Orlistat is metabolized primarily in the bowel wall to form pharmacologically inactive metabolites: M1 (four membered lactone ring hydrolysed) and M3 (M1 with N-cleaved formilleytsinovym residue).

Withdrawal. The main route of elimination is the excretion through the intestine - about 97% of the dose of the drug, of which 83% - Orlistat unchanged.

The cumulative excretion through the kidneys all substances structurally related to orlistat, is less than 2% of the dose of the drug. complete elimination time is 3-5 days. Orlistat and metabolites are excreted in bile.

Description of the pharmacological actions:

Orlistat - a specific inhibitor of gastrointestinal lipases having prolonged action. It has a therapeutic effect in the lumen of the stomach and small intestine, forming a covalent bond with the active serine site of gastric and intestinal lipases. Inactivated thus loses the ability to cleave an enzyme edible fats coming in the form of triglycerides, for soaked free fatty acids and monoglycerides. Since uncleaved triglycerides are not absorbed into the body caloric intake is reduced, which leads to weight loss.

The therapeutic effect of the drug is carried out without absorption into the systemic circulation. Action orlistat results in an increase of fat in the feces within 24-48 hours after dosing. After discontinuation of fat content in the stool usually returns to baseline within 48-72 hours.

Testimony:

Long-term treatment of patients with conditions such as:

obesity (body mass index (BMI) & ge30 kg / m2)

overweight (BMI & ge28 kg / m2), including: associated with the presence of risk factors obesity, in conjunction with a low calorie diet moderately.

Orsoten can be administered in combination with hypoglycemic agents and / or moderately low-calorie diet in patients with type 2 diabetes are overweight or obese.

Contraindications:

• hypersensitivity to orlistat or any other components of the drug
  
• chronic malabsorption syndrome
  
• cholestasia
  
• pregnancy
  
• lactation
  
• Children up to age 18 years (effectiveness and safety have been studied).
  

Application of pregnancy and breastfeeding:

According to the results of pre-clinical studies: teratogenicity and embryotoxicity when taking orlistat were observed. Clinical data on the use of orlistat during pregnancy are not available, therefore should not be administered orlistat in this time.

Data on the use during lactation are not available, so Orlistat should not be taken during lactation.

Side effect:

Adverse reactions to orlistat are mainly observed from the gastrointestinal tract and were due to an increased amount of fat in the feces. Typically, the observed side effects are mild and transient in nature. The appearance of these phenomena observed in the initial phase of treatment during the first 3 months (but not more than one occasion). Prolonged use of orlistat incidence of side effects is reduced.

There are: bloating, accompanied by discharge from the rectum, urge to defecate, fatty / oily stools, oily discharge from the rectum, watery stools, soft stools, the inclusion of fat in the feces (steatorrhea), pain / discomfort in the abdomen, increased frequency of bowel movements, pain / discomfort in the rectum, compelling urge to defecate, fecal incontinence, loss of teeth and gums of hypoglycemia in patients with type 2 diabetes, headache, anxiety, flu, fatigue, infections of the upper respiratory tract, urinary tract infection, dysmenorrhea, rare: allergic reactions (eg pruritus, rash, urticaria, angioedema, bronchoconstriction, anaphylaxis) are very rare - diverticular disease, cholelithiasis, hepatitis (possibly severe), bullous rash, increased liver transaminases and alkaline phosphatase.

Drug Interactions:

In patients receiving warfarin or other anticoagulants, and orlistat. It may be a decrease in the level of prothrombin, increasing international normalization ratio (INR), which leads to changes in haemostatic parameters.

Interaction with amitriptyline, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, nifedipine GITS, nifedipine delayed release, sibutramine, furosemide, captopril, atenolol, glibenclamide or ethanol were observed. Increases the bioavailability of pravastatin and hypolipidemic effect, increasing its plasma concentration is 30%. Weight loss can improve the metabolism in diabetic patients, thus it is necessary to reduce the dose of oral hypoglycemic agents. Orlistat treatment could potentially disrupt the absorption of fat-soluble vitamins (A, D, E. K). If the recommended intake of multivitamins, they should be taken no earlier than 2 hours after taking orlistat or at bedtime.

At the same time taking orlistat and cyclosporine, a decrease cyclosporine concentrations in blood plasma, so it is recommended to hold the cup to determine the level of concentration of cyclosporine in the blood plasma.

In patients receiving amiodarone, should be more careful to carry out clinical observation and ECG monitoring, since described cases of reducing the concentration of amiodarone in plasma.

Dosage and administration:

Inside, squeezed water just before each main meal, during meals or no later than one hour after eating.

The recommended single dose of orlistat is 1 capsule. to 120 mg. If you miss a meal or the meal contains no fat, you can skip receiving orlistat.

Orlistat dose over 120 mg 3 times a day does not increase its therapeutic effect. Duration of treatment - no more than 2 years. No dose adjustment is required for elderly patients or patients with impaired hepatic or renal function.

Safety and efficacy of orlistat in the treatment of children under the age of 18 years have not been established.

Overdose:

Cases of overdose have not been described. Acceptance of a single dose of 800 mg of orlistat or multiple doses up to 400 mg three times a day for 15 days was not accompanied by significant side reactions. In addition, the dose of 240 mg 3 times daily, to patients with obesity appointed for 6 months, has not caused a significant increase in adverse events. In the case of an overdose of orlistat is recommended to watch the patient within 24 hours.

Special instructions:

Orlistat is effective for long-term control of body weight (weight loss, maintaining it at the appropriate level and preventing re weight gain). Treatment results in improvement of orlistat risk profile and diseases associated with obesity (including hypercholesterolemia, impaired glucose tolerance, hyperinsulinemia, hypertension, type 2 diabetes mellitus) and reduction in the amount of visceral fat.

Decrease in body weight during treatment with orlistat may be accompanied by an improvement of compensation of carbohydrate metabolism in patients with type 2 diabetes, which may allow to reduce the dose of hypoglycemic drugs.

To ensure adequate nutrition, patients are advised to take multivitamin preparations.

Patients should follow the recommendations on diet. They should receive a balanced, moderately low-calorie diet containing no more than 30% of calories as fat. The daily intake of fat should be distributed to the three main meals.

The likelihood of adverse reactions from the gastrointestinal tract may increase when orlistat is taken against the background of a diet rich in fat (eg 2000 kcal / day, more than 30% of daily caloric intake comes in the form of fat, which equals about 67 grams of fat). Patients should be aware that the more accurately they are dieting (especially with respect to the allowed amount of fat), the less the likelihood of side reactions. A diet low in fat reduces the likelihood of adverse reactions from the gastrointestinal tract and help patients to monitor and regulate their fat intake.

If after 12 weeks of treatment, there was no weight loss of at least 5%, taking orlistat should be discontinued.