Xenical, 120 mg capsules 21 pcs

Xenical is a specific inhibitor of gastrointestinal lipases with prolonged action. Its therapeutic effect is carried out in the lumen of the stomach and small intestine and consists in formation of a covalent bond with the active serine site of gastric and pancreatic lipases. The inactivated enzyme loses its ability to break down food fats coming in the form of triglycerides into absorbable free fatty acids and monoglycerides.

With no triglycerides being absorbed, the resulting reduced caloric intake leads to weight loss. This way the therapeutic effect of the drug is carried out without absorption into the systemic blood flow.

Based on the results of fat content in feces, the action of orlistat starts 24-48 hours after taking the drug. After discontinuation of the drug, the fecal fat content in 48-72 h usually returns to pre-therapy levels.

Pharmacokinetics

Intake

In volunteers with normal body weight and obesity, systemic effects of the drug are minimal. Eight hours after oral administration of the drug, unchanged orlistat could not be detected in plasma, which means that its concentrations are below the 5 ng/mL level.

In general after therapeutic doses unchanged orlistat was detected in plasma only rarely, and its concentrations were extremely low (<10 ng/ml or 0.02 μmol). There were no signs of cumulation, which confirms that absorption of the drug is minimal.

Distribution

The amount of distribution could not be determined because the drug is very poorly absorbed. In vitro orlistat is more than 99% bound to plasma proteins (mainly to lipoproteins and albumin). In minimal amounts orlistat can penetrate into erythrocytes.

Metabolism

According to the data obtained in the experiment on animals, orlistat metabolism is carried out mainly in the intestinal wall. In a study in obese subjects, we found that approximately 42% of the minimal fraction of the drug that undergoes systemic absorption is due to two main metabolites, M1 (a four-member hydrolyzed lactone ring) and M3 (M1 with a cleaved N-formylleucine residue).

M1 and M3 molecules have an open β-lactone ring and are extremely weak inhibitors of lipase (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 therapeutic doses, these metabolites are considered pharmacologically inactive.

Studies in normal and overweight subjects have shown that the major route of elimination is excretion of the unabsorbed drug in the feces. About 97% of the administered dose of the drug was excreted in the feces, 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 to complete elimination of the drug from the body (in the feces and urine) is 3-5 days. The ratio of orlistat excretion routes in normal and overweight volunteers was similar. Both orlistat and M1 and M3 metabolites can be excreted with bile.

Pharmacokinetics in specific 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. Daily excretion of fat with feces was 27% of intake with food with orlistat therapy and 7% with placebo.

Indications

Long-term therapy in obese or overweight patients, including those with obesity-associated risk factors, in combination with a moderately hypocaloric diet; in combination with hypoglycemic agents (metformin, sulfonylurea derivatives and/or insulin) or a moderately hypocaloric diet in overweight or obese type 2 diabetic patients.

Active ingredient

Composition

1 capsule contains:

Active ingredient:

orlistat 120 mg;

Excipients:

Talc – 0.24 mg;

Capsule shell composition:

gelatin,

indigo carmine,

titanium dioxide.

How to take, the dosage

Long-term therapy in 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 meals or at least one hour after meals).

In combination with hypoglycemic drugs (metformin, sulfonylurea derivatives and/or insulin) or a moderately hypocaloric diet in patients with type 2 diabetes who are overweight or obese:

In adults, the recommended dose of orlistat is one 120 mg capsule with each main meal (with a meal or no later than one hour after a meal).

If meals are skipped or if the food is fat-free, 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 fats, carbohydrates and proteins should be divided into three main meals.

Interaction

No interaction with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine GITS (gastrointestinal therapy system) and slow-release nifedipine, sibutramine or alcohol (based on drug-drug interaction studies) was found. However, it is necessary to monitor INR values with concomitant therapy with warfarin or other oral anticoagulants.

A decreased absorption of vitamins D, E and beta-carotene has been noted when concomitant administration with the drug Xenical. If multivitamins are recommended, they should be taken at least 2 hours after taking Xenical or before going to bed.

Concomitant administration of Xenical and cyclosporine has decreased plasma concentrations of cyclosporine; therefore, more frequent determination of plasma concentrations of cyclosporine is recommended when cyclosporine and Xenical are taken at the same time.

In oral administration of amiodarone during therapy with Xenical, a decrease in systemic exposure of amiodarone and desethylamiodarone (by 25-30%) has been observed; however, due to the complex pharmacokinetics of amiodarone, the clinical significance of this phenomenon is unclear. Adding Xenical to long-term therapy with amiodarone may decrease the therapeutic effect of amiodarone (no studies have been performed).

The concomitant administration of Xenical and acarbose should be avoided because of the lack of data from pharmacokinetic studies.

Concomitant administration of orlistat and antiepileptic drugs has been observed to cause seizures. A causal relationship between the development of seizures and therapy with orlistat has not been established. Nevertheless, patients should be monitored for possible changes in the frequency and/or severity of seizures.

Special Instructions

Increasing the dose of orlistat above the recommended dose (120 mg 3 times daily) does not increase its therapeutic effect.

The efficacy and safety of Xenical in patients with hepatic and/or renal dysfunction and in elderly and pediatric patients (younger than 12 years) have not been studied.

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

Lowering patients’ body weight may improve metabolism in patients with diabetes and require lower doses of oral antidiabetic medications.

In clinical studies, most patients who received Xenical for 2 full years had concentrations of vitamins A, D, E, K, and beta-carotene that remained within normal limits.

In some cases, multivitamins may be prescribed for adequate intake of all nutrients and should be taken at least 2 hours after taking Xenical or before bedtime.

Contraindications

Side effects

Digestive system disorders: oily discharge from the rectum, secretion of gas, imperative defecation urges, steatorrhea, frequent defecation and fecal incontinence (as a rule, these phenomena are transient and occur in the first 3 months of treatment); rarely – pain or discomfort in the stomach, flatulence, liquid stool, pain or discomfort in the rectum.

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

Pregnancy use

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

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

Similarities