Xenical

Active material: Orlistat
When ATH: A08AB01
CCF: Anti-obesity medication – an inhibitor of gastrointestinal lipases
ICD-10 codes (testimony): E66
When CSF: 16.02.02
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, №1, turquoise, opaque; the housing black inscription “XENICAL 120”, of krыshechke – “ROCHE”; contents of capsules – pellets of white or nearly white.

*The composition of the pellets: microcrystalline cellulose, sodium carboxymethyl starch (Primogel), povidone K-30, sodium lauryl.

Excipients: talc.

Ingredients of the capsule shell: gelatin, indigokarmin, Titanium dioxide.

21 PC. – blisters (1) – packs cardboard.
21 PC. – blisters (2) – packs cardboard.
21 PC. – blisters (4) – packs cardboard.

Pharmacological action

A specific inhibitor of gastrointestinal lipases, having a lasting effect. Therapeutic action is carried in the lumen of the stomach and small intestine and is to form a covalent bond with the active serine site of gastric and pancreatic lipases. The inactivated enzyme is thus loses its ability to break down fats, from food in the form of triglycerides, on the suction free fatty acids and monoglycerides. Since triglycerides are not absorbed unsplit, It is reduced in amount through the consumption of calories, which leads to a decrease in body weight. Thus, therapeutic effect is carried out without absorption into the systemic circulation.

Based on the amount of fat in the feces data show, that the effect of the drug begins within 24-48 h after administration. After discontinuation fat content in the stool through 48-72 h usually returns to the level, took place prior to initiating therapy.

Pharmacokinetics

Absorption

In volunteers with normal body weight and obesity is minimal systemic exposure of the drug. After oral administration of orlistat is practically not absorbed from the gastrointestinal tract. Through 8 hours after ingestion unmodified orlistat plasma could not be determined, meaning, that its concentration in blood plasma below 5 ng / ml.

Generally, after administration of therapeutic doses of unmodified identify orlistat plasma succeeded only rarely, while its concentration were extremely small (<10 ng / mL or 0.02 mmol). Signs of cumulation no, that confirms, that the drug absorption is minimal.

Distribution

V_d can not be set due to the very low systemic absorption of orlistat. Plasma protein binding (primarily, lipoproteins and albumin) in vitro составляет 99%. The minimum quantities orlistat can penetrate into the red blood cells.

Metabolism

Judging from the data, obtained in animal studies, the metabolism of orlistat is carried out, mainly, in the gut wall. In a study in obese installed, roughly 42% that the minimum fraction of the drug, which undergoes systemic absorption, It falls into two major metabolite – M1 (four-membered lactone ring hydrolyzed) and M3 (M1 is cleaved residue N-formilleytsina).

The molecules of M1 and M3 have an open β-lactone ring and extremely weak lipase inhibiting (respectively 1000 and 2500 times weaker, Cem orlistat). In view of this low inhibitory activity and low plasma concentrations of (average, 26 ng / ml 108 ng / ml) after administration of therapeutic doses of these metabolites are considered as pharmacologically inactive.

Deduction

Studies in patients with normal and overweight showed, what 97% of the dose is excreted in the feces of orlistat, of them 83% – in unchanged form. The cumulative renal excretion of substances, structurally related to orlistat, is less than 2% of the dose. The period of complete elimination from the body Orlistat (with feces and urine) – 3-5 d. Orlistat and its metabolites are excreted in bile.

Value for ways to derive the orlistat volunteers with normal and overweight was similar.

Pharmacokinetics in special clinical situations

Plasma concentrations of orlistat and its metabolites (M1 and M3) children do not differ from those of adults when compared to the same doses of the drug.

The daily fat excretion in feces was 27% from taking food when orlistat and 7% – placebo.

Testimony

- Long-term treatment of patients with obese patients or overweight, incl. associated with obesity risk factors, combined with moderately reduced-calorie diet;

- In combination with hypoglycemic drugs (metformin, sulfonylureas and / or insulin) or moderately hypocaloric diet in patients with diabetes mellitus type 2 overweight or obese.

Dosage regimen

To Adult The recommended dose of Xenical^® is 120 mg (1 capsule) 3 times / day with each main meal (during meals or no later than one hour after a meal). If you miss a meal, or if the food does not contain fat, the intake of Xenical^® You can also skip.

Increasing the dose of Xenical^® More than recommended (120 mg 3 times / day) It does not enhance its therapeutic effect.

To elderly patients, patients with impaired liver or kidney function dose adjustment is not required.

The efficacy and safety of Xenical^® in children and adolescents up to 18 years not installed.

Side effect

Determination of the frequency of adverse reactions: Often (≥ 1/10), often (≥ 1/100 and < 1/10), sometimes (≥ 1/1000 and < 1/100), rarely (≥ 1/10 000 and < 1/1000), rarely (< 1/10 000), including individual cases.

Adverse reactions to Xenical^® arose mainly from the gastrointestinal tract, and were caused by the pharmacological action of the drug, prevents the absorption of fat meals.

From the digestive system: Often – oily discharge from the rectum, gassing with a number of discharge, urgency to defecate, celiac disease, increased frequency of bowel movements, loose stools, flatulence, pain and discomfort in the abdomen. The frequency of these adverse effects increase with increasing fat content in the food. Patients should be informed about the possibility of adverse reactions and train, how to eliminate them through better compliance with a diet low in fat. Usually, these adverse reactions are mild and transient. They arose in the early stages of treatment (first 3 of the month), and the majority of patients had no more than one episode of these reactions.

Often – upholstered chairs, pain or abdominal discomfort, scatacratia, flatulence, loss of teeth, Right defeat.

Rarely – increase in liver transaminases and alkaline phosphatase, in some cases – hepatitis (a causal relationship with the reception Xenical^® or pathophysiological mechanisms of development have not been established.)

Frequency unknown – rectal bleeding, diverticulitis, pancreatitis, cholelithiasis.

Allergic reactions: in some cases – itch, rash, hives, angioedema, bronchospasm and anaphylactic reactions.

Other: Often – headache, infections of the upper respiratory tract, flu; often – infections of the lower respiratory tract, dysmenorrhoea, alarm, weakness, urinary tract infection; rarely – bullous rash.

In patients with diabetes mellitus type 2 the nature and frequency of adverse events were comparable to those in patients without diabetes in overweight and obese. The only new side effects, occurs with a frequency >2% and ≥1 % compared to placebo, were hypoglycemic states (that could result from improving the compensation of carbohydrate metabolism) and flatulence.

When concomitant administration of Xenical^® and anticoagulants reduce reported cases of prothrombin, an increase in INR.

Contraindications

- Chronic malabsorption syndrome;

- Cholestasis;

- Hypersensitivity to the drug.

Pregnancy and lactation

Category B. Xenical^® should not be used during pregnancy due to the lack of reliable clinical data, confirming the safety of its use.

Withdrawal of orlistat in breast milk has not been studied, therefore, it should not take Xenical^® during breastfeeding.

IN experimental studies in animals revealed no teratogenic and embryotoxic effect of orlistat.

Cautions

Xenical^® effective long-term weight control programs (body weight reduction and long-term maintenance of its new level, preventing re-weight gain). The efficacy of Xenical^® It appears to improve the profile of risk factors and disease, concomitant obesity (such as hypercholesterolemia, diabetes mellitus type 2, impaired glucose tolerance, giperinsulinemija, arterial hypertension), and to reduce the amount of visceral fat.

If concomitant therapy with warfarin or other anticoagulants is necessary to monitor the INR.

When used in combination with hypoglycemic agents, how metformin, sulfonylureas and / or insulin, in patients with diabetes mellitus type 2 Overweight (BMI ≥ 28 kg / m²) or obese (BMI ≥ 30 kg / m²) Xenical^®, combined with moderately reduced-calorie diet, It provides a further improvement of compensation of carbohydrate metabolism.

In clinical trials, most patients, received Xenical^® during 2 full years, the concentration of vitamin A (incl. betakarotena), D, E and K remained in the normal range.

To ensure an adequate supply of nutrients in the body can be assigned to a multivitamin, which should be no less than 2 hours after taking Xenical^® or at bedtime.

The patient should receive balanced, mildly hypocaloric diet, containing not more than 30% daily calories as fat. It is recommended to consume food, containing plenty of fruits and vegetables. The daily intake of fat, carbohydrate and protein should be distributed into three main reception.

The probability of adverse reactions from the gastrointestinal tract may increase, unless Xenical^® take on the background of power, ketogenic (eg, 2000 kcal / day, of which more than 30% – a fat, that is approximately 67 g fat). The daily intake of fat should be distributed on 3 the main reception.

Weight loss, associated with the use of Xenical^®, It leads to an improvement of carbohydrate metabolism at diabetes type 2, which may allow or require a dose reduction of hypoglycemic drugs.

Overdose

In clinical studies in patients with normal weight and obese patients receiving a single dose 800 mg or multiple reception 400 mg 3 times / day for 15 days did not lead to significant adverse reactions. There is experience with the drug at 240 mg 3 times / day for 6 Months, it was not accompanied by a significant increase in the frequency of adverse events.

In cases of overdose of Xenical^® the absence of any reported adverse events, any adverse events did not differ from those, observed while taking the drug at therapeutic doses.

Treatment: in the case of severe overdose recommended under medical surveillance for 24 no. According to studies in humans and animals considered, that any systemic effects, which could be associated with the properties of orlistat lipazoingibiruyuschimi, should be rapidly reversible.

Drug Interactions

Not established drug interactions, while the use of Xenical^® with amitriptyline, atorvastatin, ʙiguanidami, digoksinom, fiʙratami, fluoxetine, lozartanom, phenytoin, varfarinom, oral contraceptives, pravastatin, phentermine, nifedipine GITS (gastrointestinal therapeutic system) and a slow-release nifedipine, sibutramine, ethanol (Based on studies of the interaction between drugs).

With simultaneous use of Xenical^® may reduce the absorption of fat-soluble vitamins A (incl. betakarotena), D, E, and K.

With simultaneous use of Xenical^® and cyclosporine showed a decrease of plasma concentrations of cyclosporine, Therefore, when this combination is recommended more frequent determination of cyclosporin concentrations in plasma.

In the appointment of amiodarone during therapy Ksenikalom^® marked reduction in the bioavailability of amiodarone and dezetilamiodarona (on 25-30%), However, due to the complex pharmacokinetics of amiodarone the clinical significance of this effect is not clear. Adding Xenical^® to long-term therapy with amiodarone may lead to a reduction in the therapeutic effect of amiodarone.

Avoid simultaneous reception Xenical^® acarbose, and due to the lack of data pharmacokinetic studies.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, a dry place at a temperature no higher than 25 ° C. Shelf life – 3 year. Do not use after the expiry date, on the package.