Xenical, 120 mg , 84 pcs.

1 capsule contains: 

Active substance:

 orlistat 120 mg;

Excipients:

talc - 0.24 mg;

Capsule shell composition :

gelatin,

indigo carmine,

titanium dioxide.

Xenical is a long-lasting specific inhibitor of gastrointestinal lipases. 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 site of gastric and pancreatic lipases.

At the same time, the inactivated enzyme loses its ability to break down food fats, which come in the form of triglycerides, into absorbed free fatty acids and monoglycerides. Since the undigested triglycerides are not absorbed, the resulting decrease in caloric intake in 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.

Judging by the results of the fat content in the feces, the effect of orlistat begins 24–48 hours after ingestion. After discontinuation of the drug, the fat content in feces after 48-72 hours usually returns to the level that had occurred before the start of therapy.

Pharmacokinetics

Suction

In volunteers with normal body weight and obesity, the systemic effect of the drug is minimal. 8 hours after oral administration of the drug, unchanged orlistat in plasma could not be determined, which means that its concentrations are below 5 ng / ml.

In general, after taking therapeutic doses, it was possible to detect unchanged orlistat in plasma only in rare cases, while its concentrations were extremely low (<10 ng / ml or 0.02 μmol). There were no signs of cumulation, which confirms that the absorption of the drug is minimal.

Distribution

The volume of distribution cannot be determined, since the drug is very poorly absorbed. In vitro, orlistat binds more than 99% to plasma proteins (mainly lipoproteins and albumin). In minimal amounts, orlistat can penetrate into erythrocytes.

Metabolism

Judging by the data obtained in an experiment on animals, the metabolism of orlistat is carried out mainly in the intestinal wall. In a study in obese individuals, it was found that approximately 42% of the minimal fraction of the drug that undergoes systemic absorption is accounted for by two 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 (respectively, 1000 and 2500 times weaker than orlistat). Given such low inhibitory activity and low plasma concentrations (on average 26 and 108 ng / ml, respectively) after taking therapeutic doses, these metabolites are considered pharmacologically inactive.

Withdrawal

Studies in persons with normal and overweight have shown that the main route of elimination is the excretion of the unabsorbed drug in the feces. About 97% of the taken dose of the drug was excreted with feces, and 83% - in the form of unchanged orlistat.

The cumulative renal excretion of all substances structurally related to orlistat is less than 2% of the dose taken. The time until complete elimination of the drug from the body (with feces and urine) is 3–5 days. The ratio of the routes of elimination of orlistat in volunteers with normal and overweight was the same. Both orlistat and 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 the drug. The daily excretion of fat with feces was 27% of the intake with food with orlistat therapy and 7% with placebo.

Long-term therapy of obese or overweight patients, incl. having risk factors associated with obesity, in combination with a moderately hypocaloric diet; in combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and / or insulin) or a moderately hypocaloric diet in overweight or obese type 2 diabetes mellitus patients.

Due to the lack of clinical data, Xenical should not be administered to pregnant women.

The excretion of orlistat in breast milk has not been studied, so it should not be taken while breastfeeding.

• hypersensitivity to the drug or any other components contained in the capsule;
• chronic malabsorption syndrome;
• cholestasis.

On the part of the digestive system: oily discharge from the rectum, gas, urge to defecate, steatorrhea, increased frequency of bowel movements and fecal incontinence (as a rule, these phenomena are transient and occur in the first 3 months of treatment); rarely - abdominal pain or discomfort, flatulence, loose stools, pain or discomfort in the rectum.

Allergic reactions: skin rash, itching, angioedema, anaphylactic reactions.

No interactions with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine GITS (gastrointestinal therapeutic system with medication or medication) and nifedolem drug interactions studies). However, it is necessary to monitor the INO values ​​with concomitant therapy with warfarin or other oral anticoagulants.
When taken simultaneously with the drug Xenical, a decrease in the absorption of vitamins D, E and beta-carotene was noted. If multivitamins are recommended, they should be taken at least 2 hours after taking Xenical or at bedtime.

With the simultaneous administration of the drug Xenical and cyclosporine, a decrease in plasma concentrations of cyclosporine was noted, therefore, more frequent determination of the concentrations of cyclosporine in plasma is recommended while taking cyclosporine and the drug Xenical.

With oral administration of amiodarone during therapy with Xenical, a decrease in the systemic exposure of amiodarone and desethylamiodarone (by 25-30%) was noted, however, due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is not clear. The addition of Xenical to long-term therapy with amiodarone may lead to a decrease in the therapeutic effect of amiodarone (no studies have been conducted).
Simultaneous administration of the drug Xenical and acarbose should be avoided, due to the lack of data from pharmacokinetic studies.

With the simultaneous administration of orlistat and antiepileptic drugs, there have been cases of seizures. A causal relationship between the development of seizures and orlistat therapy has not been established. However, patients should be monitored for possible changes in the frequency and / or severity of seizures.

Long-term therapy of obese or overweight patients, including those 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 one 120 mg capsule with each main meal ( during meals or no later than an hour after meals).

In combination with hypoglycemic drugs (metformin, sulfonylureas and / or insulin) or a moderately hypocaloric diet in overweight or obese type 2 diabetes mellitus patients:
in adults, the recommended dose of orlistat is one 120 mg capsule with each main meal (in meal time or no later than an hour after eating).

If a meal is skipped or if the food does not contain fat, then you can also skip taking Xenical.
The drug should be taken in conjunction with a balanced, moderately hypocaloric diet containing no more than 30% of calories as fat. The daily intake of fats, carbohydrates and proteins must be divided into three main doses.

An increase in 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 Xenical 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.

During therapy with Xenical, the patient should receive a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fats. With a higher fat content in the diet, the likelihood of adverse reactions from the gastrointestinal tract increases.

A decrease in the body weight of patients can improve the metabolism in patients with diabetes mellitus and require a reduction in the dose of oral antidiabetic drugs.

In clinical studies, in most patients who received Xenical for 2 full years, the concentrations of vitamins A, D, E, K and beta-carotene remained within the normal range. In some cases, for an adequate intake of all nutrients in the body, multivitamins can be prescribed, which should be taken at least 2 hours after taking Xenical or before bedtime.

Capsules