Xenical, 120mg capsules, 84pcs

Composition

1 capsule contains:  

Active ingredient:

orlistat 120 mg; Excipients:

talcum powder – 0.24 mg.

Capsule shell composition:

gelatin, indigo carmine, titanium dioxide.

Pharmacological action

Xenical is a long-acting 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.

In this case, the inactivated enzyme loses its ability to break down food fats coming in the form of triglycerides into absorbed free fatty acids and monoglycerides. Since undivided triglycerides are not absorbed, the resulting reduction in caloric intake 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 feces, the effect of orlistat begins 24-48 hours after ingestion. After discontinuation of the drug, the fat content in the stool usually returns to the level that occurred before the start of therapy in 48-72 hours.

Pharmacokinetics

Suction

In volunteers with normal body weight and obesity, the systemic effect of the drug is minimal. 8 hours after oral use of the drug, unchanged orlistat could not be determined in plasma, which means that its concentrations are below the level of 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 ( There were no signs of accumulation, 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 red blood cells.

Metabolism

Judging by the data obtained in an animal experiment, orlistat metabolism is mainly carried out in the intestinal wall. In a study in obese individuals, it was found that approximately 42% of the minimum fraction of the drug that undergoes systemic absorption is accounted for by two main metabolites — M1 (a four-membered hydrolyzed lactone ring) and M3 (M1 with a cleaved N-formylleucine residue).

M1 and m3 molecules have an open beta-lactone ring and are extremely weak in lipase inhibition (1000 and 2500 times weaker, respectively, 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.

Deduction

Studies in individuals with normal and overweight body weight have shown that the main route of elimination is the elimination of non-absorbed drug with feces. About 97% of the drug dose was excreted in the feces, and 83% – in the form of unchanged orlistat.

The total renal excretion of all substances structurally related to orlistat is less than 2% of the dose taken. The time to complete elimination of the drug from the body (with feces and urine) is 3-5 days. The ratio of orlistat elimination routes in volunteers with normal and overweight body weight was the same. Both orlistat and the M1 and M3 metabolites 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 in the feces was 27% of the food intake with orlistat and 7% with placebo.

Indications

Long-term therapy of obese or overweight patients, including those with obesity-associated risk factors, in combination with a moderately hypocaloric diet; in combination with hypoglycemic drugs (metformin, sulfonylureas and/or insulin) or a moderately low-calorie diet in patients with type 2 diabetes mellitus who are overweight or obese.

Use during pregnancy and lactation

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

The elimination of orlistat in breast milk has not been studied, so it should not be taken during breast-feeding.

Contraindications

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

Side effects

From the digestive system: oily discharge from the rectum, gas release, imperative urge to defecate, steatorrhea, increased bowel movements and fecal incontinence (usually 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, pruritus, angioedema, anaphylactic reactions.

Interaction

There were no interactions with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine GITS (gastro-intestinal Therapeutic System) and slow-release nifedipine, sibutramine or alcohol (based on drug-drug interaction studies). However, it is necessary to monitor the INR values during concomitant therapy with warfarin or other oral anticoagulants. When taken concomitantly with Xenical, there was a decrease in the absorption of vitamins D, E and beta-carotene. If a multivitamin is recommended, it should be taken at least 2 hours after taking Xenical or before bedtime.

When taking Xenical and cyclosporine at the same time, a decrease in plasma concentrations of cyclosporine was noted, therefore, more frequent determination of cyclosporine concentrations in plasma is recommended when taking cyclosporine and Xenical at the same time.

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

Seizures have been reported when orlistat and antiepileptic drugs are co-administered. 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.

How to take, course of use and dosage

Long-term therapy of obese or overweight patients, including those with obesity-associated risk factors, 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 (with a meal or no later than an hour after a meal).

In combination with hypoglycemic drugs (metformin, sulfonylureas and/or insulin) 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 one 120 mg capsule with each main meal (during a meal or no later than an hour after a meal).

If the meal is skipped or if the food does not contain fat, then the drug Xenical can also be skipped. The drug 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 fat, carbohydrates, and protein should be divided into three main meals.

Special instructions

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.

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) not investigated.

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

Reducing patients ‘ body weight may improve metabolism in patients with diabetes mellitus and require a reduction in the dose of oral antidiabetic drugs.

In clinical studies, the majority of patients treated with Xenical for 2 full years had concentrations of vitamins A, D, E, K, and beta-carotene within the normal range. In some cases, for adequate intake of all nutrients in the body, you can prescribe multivitamins, which should be taken at least 2 hours after taking Xenical or before going to bed.

Form of production

Capsules

Storage conditions

In a place protected from moisture, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Orlistat

Conditions of release from pharmacies

By prescription

Dosage form

Capsules