Xenalten, 120 mg capsules, 84 pcs.

Xenalten is an inhibitor of gastrointestinal lipases.

Pharmacodynamics

A specific inhibitor of gastrointestinal lipases. It forms covalent bond with active serine site of gastric and pancreatic lipases in lumen of stomach and small intestine. The inactivated enzyme loses its ability to break down food fats coming in the form of triglycerides (TGs). The unreleased TGs are not absorbed, and the resulting decrease in caloric intake leads to a decrease in body weight. Increases the concentration of fat in stools 24-48 hours after ingestion. Provides effective weight control and reduction of fat depots.

The activity does not require systemic absorption of orlistat, at the recommended therapeutic dose (120 mg 3 times daily) it inhibits approximately 30% absorption of dietary fat.

Pharmacokinetics

Absorption is low; 8 hours after oral administration unchanged orlistat is not detected in plasma (concentration below 5 ng/ml).

The systemic exposure of orlistat is minimal. After oral administration of 360 mg of radioactively labeled ¹⁴C-orlistat, peak plasma radioactivity was reached after approximately 8 h; the concentration of unchanged orlistat was close to the limit of determination (less than 5 ng/mL). In therapeutic studies that included monitoring of patient plasma samples, unchanged orlistat was determined sporadically in plasma, and its concentrations were low (less than 10 ng/mL), with no evidence of accumulation, consistent with minimal absorption of the drug.

In vitro Orlistat binds more than 99% to plasma proteins, mainly to lipoproteins and albumin. Orlistat minimally penetrates into erythrocytes. It is metabolized mainly in the gastrointestinal wall to form pharmacologically inactive metabolites M1 (hydrolyzed four-membered lactone ring) and M3 (M1 with a detached N-formylleucine residue). In a study in obese patients taking oral ¹⁴C-orlistat, the 2 metabolites, M1 and M3, accounted for about 42% of total plasma radioactivity. M1 and M3 have an open beta-lactone ring and exhibit extremely weak inhibitory activity against lipases (1000 and 2500 times weaker than orlistat, respectively). Taking into account the low activity and low concentrations of the metabolites in plasma (about 26 ng/ml and 108 ng/ml for M1 and M3 respectively 2-4 h after taking orlistat at therapeutic doses), these metabolites are considered to be pharmacologically insignificant. The main metabolite M1 has a short T_1/2 (about 3 h), the second metabolite is excreted more slowly (T_1/2 is 13.5 h). In obese patients, the C_ss of metabolite M1 (but not M3) increases in proportion to the dose of orlistat. After a single oral intake of 360 mg of ¹⁴C orlistat in normal-weight and obese patients, excretion of unabsorbed orlistat through the intestine was the major route of excretion. Orlistat and its metabolites M1 and M3 are also excreted in the bile. About 97% of the administered radioactively labeled substance was excreted in the feces, including 83% unchanged.

The cumulative renal excretion of total radioactivity when 360 mg of ¹⁴C-orlistat was less than 2%. Total elimination time with feces and urine was 3-5 days. The excretion of orlistat appeared similar in patients with normal body weight and those with obesity. Based on limited data, T_1/2absorbed orlistat ranged from 1-2 h.

Indications

The main purpose of Xenaltene is obesity or excess body weight. It can be used in combination with a hypocaloric diet. In addition, the medication is often used to reduce the likelihood of gaining weight again after successful weight loss. It can also be used for risk factors such as diabetes, dyslipidemia, and arterial hypertension.

Active ingredient

Orlistat

Composition

1 capsule contains:

The active ingredient: orlistat 120 mg;

Excipients: MCC, 59.6 mg; sodium carboxymethyl starch (sodium starch glycolate), 38 mg; sodium lauryl sulfate, 10 mg; povidone, 10 mg; talc, 2.4 mg

How to take, the dosage

Overly, 120 mg 3 times daily with each meal or no later than 1 hour after a meal (if the food is fat-free, you can skip it).

Interaction

Orlistat has no effect on the pharmacokinetics of alcohol, digoxin (administered in a single dose) and phenytoin (administered in a single dose of 300 mg), on the bioavailability of nifedipine (sustained-release tablets), ovulatory-suppressive activity of oral contraceptives, pharmacokinetics (both R- and S-enantiomers), and pharmacodynamics (prothrombin time and factor VII levels) of warfarin. Alcohol had no effect on the pharmacodynamics (fecal fat excretion) and systemic exposure of orlistat.

Preliminary data shows that concomitant use of orlistat and cyclosporine decreases plasma levels of the latter (orlistat and cyclosporine should not be taken simultaneously; to decrease the possibility of drug interaction, cyclosporine should be taken 2 hours before or 2 hours after taking orlistat). Orlistat decreases absorption of beta-carotene contained in food supplements by 30% and inhibits absorption of vitamin E (in the form of tocopherol acetate) by approximately 60%.

Limits the bioavailability and hypolipidemic effect of pravastatin by increasing its plasma concentration by 30%. Reduces absorption of fat-soluble vitamins. The effect of orlistat on the absorption of vitamins D, A contained in supplements is currently unknown. Although levels of carboxylated osteocalcin, a marker of dietary vitamin K intake, were not altered by taking orlistat, people who took orlistat showed a trend toward lower vitamin K levels.

Lowering body weight may improve metabolism in diabetic patients, and therefore the dose of oral hypoglycemic drugs should be reduced. No clinically significant interactions with digoxin, phenytoin, oral contraceptives, nifedipine, glibenclamide, furosemide, captopril, atenolol, and ethanol were noted.

Special Instructions

With caution use in pregnancy and lactation, with a history of hyperoxaluria, nephrolithiasis (calcium oxalate stones).

When treating, it is necessary to maintain a balanced, low-calorie diet containing no more than 30% of calories in the form of fat and enriched with fruits and vegetables (additional prescription of multivitamins is possible to compensate for the reduced absorption of fat-soluble vitamins).

Before prescribing orlistat, an organic cause of obesity, such as hypothyroidism, should be excluded. The likelihood of gastrointestinal side effects increases with high dietary fat content (more than 30% of daily calories). Daily intake of fats, carbohydrates and proteins should be distributed between three main meals. Since orlistat reduces absorption of some fat-soluble vitamins, patients should take multivitamin preparations containing fat-soluble vitamins to ensure their adequate intake. In addition, vitamin D and beta-carotene levels may be lower in obese patients than in people who are not obese. Multivitamins should be taken 2 hours before or 2 hours after taking orlistat, e.g., before bedtime. Taking orlistat in doses greater than 120 mg 3 times a day does not provide additional benefit. In patients taking orlistat and cyclosporine concomitantly, more frequent monitoring of plasma cyclosporine is required.

In patients who did not receive prophylactic vitamin supplements, two or more consecutive visits during the first and second years of treatment with orlistat showed decreased plasma vitamin levels. Urinary oxalate levels may increase in some patients on orlistat. As for other drugs for weight loss, in some groups of patients (e.g., with anorexia nervosa or bulimia) there is a possibility of orlistat abuse.
Because absorption of vitamin K may decrease when taking orlistat, clotting parameters should be closely monitored in patients receiving orlistat on long-term continuous warfarin.

The induction of weight loss with orlistat may be combined with improved metabolic control of diabetes, which would require reduction of doses of oral hypoglycemic agents (sulfonylurea derivatives, metformin, etc.) or insulin.

The treatment should not last more than 2 years. Xenalten is not intended for use in pediatric practice.

Contraindications

• high sensitivity to orlistat or other drug components
• syndrome of malabsorption
• cholestasischolestasis;
• concomitant use with cyclosporine;
• pregnancy and lactation;
• age below 18 years of age.

With caution: history of hyperoxaluria, nephrolithiasis (calcium oxalate stones).

Side effects

Gastrointestinal organs: oily discharge, flatulence, urgent defecation, oily/oily stools, increased frequency of defecation, stool incontinence, abdominal pain/discomfort, nausea, infectious diarrhea, rectal pain/discomfort, vomiting.

Nervous system and sensory organs: headache, dizziness, fatigue, sleep disturbance, anxiety, depression.

Respiratory system disorders: upper respiratory tract infections, lower respiratory tract infections, ENT symptoms, otitis media.

Urogenital system disorders: irregular menstrual cycle, vaginitis, urinary system infections.

Musculoskeletal system: back pain, pain in the lower extremities, arthralgia, myalgia, joint dysfunction, tendonitis.

Skin disorders: rash, dry skin.

Others: flu, swelling of the feet, allergic reactions.

Similarities

Xenical, Orsotene, Orsotene Slim, Listata, Listata Mini, Orlistat