Orlistat
Diet and exercise are an integral part of a weight loss program. It is recommended to begin a dietary program and exercise before starting therapy with Orlistat.
While taking Orlistat, you must adhere to a fractional, balanced, moderately hypocaloric diet, with a fat content of no more than 30% of the daily calorie intake (for example, with a diet of 2000 kcal/day, fat intake should be no more than 66 g/day). You should adhere to the recommendations received regarding diet and physical activity, both during and after stopping the drug.
The use of the drug Orlistat leads to an increase in fat content in stool already 24-48 hours after the start of administration. After discontinuation of Orlistat, stool fat content usually returns to baseline levels within 48 to 72 hours.
Following a low-fat diet reduces the likelihood of adverse reactions from the gastrointestinal tract.
Taking orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E, K and beta-carotene). The vast majority of patients receiving orlistat during the four-year clinical studies had vitamin A, D, E, K and beta-carotene concentrations within normal limits. For preventive purposes, it is recommended to take multivitamins at night.
Since weight loss is usually accompanied by an improvement in carbohydrate metabolism, patients with type 2 diabetes mellitus should consult a doctor before starting therapy with Orlistat and, if necessary, adjust the dose of hypoglycemic drugs.
A decrease in body weight during treatment may be accompanied by a decrease in blood pressure and the concentration of TC in the blood plasma. Patients taking antihypertensive or lipid-lowering drugs should consult a doctor and, if necessary, adjust the dose of these drugs.
In clinical studies, no interaction was observed between oral contraceptives and orlistat. However, orlistat may indirectly reduce the bioavailability of oral contraceptives, which may lead to the development of unwanted pregnancy. It is recommended to use additional methods of contraception in case of acute diarrhea.
Patients with kidney disease should consult a doctor, as hyperoxaluria and nephropathy may develop.
Patients taking amiodarone, warfarin or other oral anticoagulants should also consult a physician before starting orlistat therapy as changes in the INR may occur.
Patients should stop taking Orlistat and consult a doctor if symptoms occur: icteric discoloration of the sclera or skin, itching, dark urine and loss of appetite.
Cases of rectal bleeding have been observed with the use of orlistat. If this phenomenon occurs, the patient should consult a doctor.
When orlistat and levothyroxine sodium are used together, hypothyroidism and/or decreased control of hypothyroidism may develop. Patients taking levothyroxine sodium should consult their doctor before starting treatment with orlistat, because It may be necessary to take orlistat and levothyroxine sodium at different times, and the dose of levothyroxine sodium may need to be adjusted.
Patients taking antiepileptic drugs should consult their doctor before starting treatment with orlistat, because they should be monitored for possible changes in the frequency and severity of seizures. In these cases, the possibility of taking orlistat and antiepileptic drugs at different times should be considered.
Patients should consult their physician before using orlistat concomitantly with antiretroviral drugs used to treat HIV infection. Orlistat may reduce the absorption of antiretroviral drugs and negatively affect their effectiveness.
Orlistat-Akrikhin caps 120 mg N84 (Akrikhin)
Orlistat is a specific, long-acting inhibitor of gastrointestinal lipases. It acts in the lumen of the stomach and small intestine, forming a covalent bond with the active serine site of gastric and pancreatic lipases. An inactivated enzyme is unable to break down food fats, which come in the form of triglycerides, into absorbable free fatty acids and monoglycerides. Unsplit triglycerides are not absorbed, and therefore the intake of calories into the body decreases, which leads to a decrease in body weight. The therapeutic effect of the drug is carried out without absorption into the systemic circulation. Increases the concentration of fat in feces 24-48 hours after administration. Provides effective control of body weight, reduction of fat storage. Efficacy Obese patients In clinical studies, patients taking orlistat experienced greater weight loss compared to patients on diet therapy. Weight loss began within the first 2 weeks after the start of treatment and lasted from 6 to 12 months, even in patients with a negative response to diet therapy. Over the course of 2 years, there was a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, compared to placebo, there was a significant reduction in body fat. Orlistat is effective in preventing weight gain. Re-gain of body weight, no more than 25% of what was lost, was observed in approximately half of the patients, and in half of these patients, no re-gain of body weight was observed or even a further decrease was observed. Obese patients with type 2 diabetes mellitus In clinical studies lasting 6 months to 1 year, overweight or obese patients with type 2 diabetes mellitus receiving orlistat experienced greater weight loss compared to patients treated with diet therapy alone. Body weight loss occurred mainly due to a decrease in the amount of fat in the body. It should be noted that before the start of the study, despite taking hypoglycemic agents, patients often had insufficient glycemic control. However, with orlistat therapy, a statistically and clinically significant improvement in glycemic control was observed. In addition, during orlistat therapy, a decrease in doses of hypoglycemic agents, insulin concentrations, and a decrease in insulin resistance were observed. Reducing the risk of developing type 2 diabetes in obese patients In a 4-year clinical trial, orlistat was shown to significantly reduce the risk of developing type 2 diabetes (by approximately 37% compared to placebo). The degree of risk reduction was even greater in patients with baseline impaired glucose tolerance (approximately 45%). There was greater weight loss in the orlistat treatment group compared to the placebo group. Maintaining body weight at a new level was observed throughout the entire study period. Moreover, compared with placebo, patients treated with orlistat showed a significant improvement in their metabolic risk factor profile. Pubertal Obesity In a 1-year clinical study in obese adolescents, orlistat was associated with a decrease in body mass index compared with placebo, which even increased body mass index. In addition, patients in the orlistat group showed a decrease in fat mass, as well as waist and hip circumferences compared to the placebo group. Also, patients receiving orlistat therapy experienced a significant reduction in diastolic blood pressure compared to the placebo group.
Orlistat-akrikhin 120 mg 42 pcs. Polpharma capsules Akrikhin
pharmachologic effect
Inhibiting gastrointestinal lipases.
Composition and release form Orlistat-akrikhin 120 mg 42 pcs. Polpharma capsules Akrikhin
Capsules - 1 capsule:
- active substance: 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;
- capsule (hard, gelatin): titanium dioxide; gelatin; Patented blue dye.
The average weight of the capsule contents is 240 mg.
Capsules, 120 mg. 7 or 21 caps. in blister packs made of PVC film and printed varnished aluminum foil.
1, 2, 3, 4, 6, 12 blister packs are placed in a cardboard pack.
Description of the dosage form
Capsules No. 1 with a blue body and cap.
Capsule contents: white or almost white granules.
Directions for use and doses
Orally, 120 mg (1 cap.) 3 times a day during each meal or no later than 1 hour after meals (if the food does not contain fat, then the dose can be skipped).
Pharmacodynamics
Specific inhibitor of gastrointestinal lipases. Forms a covalent bond with the active serine site of gastric and pancreatic lipases in the lumen of the stomach and small intestine. The inactivated enzyme loses its ability to break down food fats, which come in the form of triglycerides (TG). Unsplit TG are not absorbed, and the resulting decrease in caloric intake into the body leads to a decrease in body weight. Increases the concentration of fat in feces 24–48 hours after administration. Provides effective control of body weight, reduction of fat storage.
Systemic absorption of orlistat is not required for activity to occur; at the recommended therapeutic dose (120 mg 3 times a day), it inhibits the absorption of dietary fat by approximately 30%.
Pharmacokinetics
Absorption - low; 8 hours after oral administration, unchanged orlistat is not detected in plasma (concentration below 5 ng/ml).
Systemic exposure to orlistat is minimal. After oral administration of 360 mg of radiolabeled 14C-orlistat, peak radioactivity in plasma was reached after approximately 8 hours; the concentration of unchanged orlistat was close to the limit of detection (less than 5 ng/ml). In therapeutic studies that included monitoring of patient plasma samples, unchanged orlistat was detected sporadically in plasma and concentrations were low (less than 10 ng/mL) with no evidence of accumulation, consistent with minimal absorption of the drug.
In vitro, orlistat is more than 99% bound to plasma proteins, mainly lipoproteins and albumin. Orlistat penetrates minimally into red blood cells. Metabolized mainly in the wall of the gastrointestinal tract with the formation of pharmacologically inactive metabolites M1 (hydrolyzed four-membered lactone ring) and M3 (M1 with a cleaved N-formylleucine residue). In a study of obese patients ingesting 14C-orlistat, 2 metabolites, M1 and M3, accounted for approximately 42% of total plasma radioactivity. M1 and M3 have an open beta-lactone ring and exhibit extremely weak inhibitory activity against lipases (compared to orlistat, 1000 and 2500 times weaker, respectively). Given the low activity and low plasma concentrations of metabolites (about 26 ng/ml and 108 ng/ml for M1 and M3, respectively, 2–4 hours after taking orlistat in therapeutic doses), these metabolites are considered pharmacologically insignificant. The main metabolite M1 has a short T1/2 (about 3 hours), the second metabolite is excreted more slowly (T1/2 - 13.5 hours). In obese patients, the Css of metabolite M1 (but not M3) increases proportionally to the dose of orlistat. After a single oral dose of 360 mg of 14C-orlistat in normal weight and obese patients, excretion of unabsorbed orlistat through the intestine was the main route of elimination. Orlistat and its metabolites M1 and M3 are also excreted in bile. About 97% of the administered radioactively labeled substance was excreted in feces, incl. 83% - unchanged.
Cumulative renal excretion of total radioactivity with 360 mg 14C-orlistat was less than 2%. The time for complete elimination in feces and urine is 3–5 days. Elimination of orlistat was similar in normal-weight and obese patients. Based on limited data, T1/2 of absorbed orlistat ranges from 1 to 2 hours.
Indications for use Orlistat-akrikhin 120 mg 42 pcs. Polpharma capsules Akrikhin
- treatment of obesity, incl. reduction and maintenance of body weight, in combination with a hypocaloric diet;
- reducing the risk of weight gain again after its initial loss.
Orlistat is indicated for obese patients with a body mass index (BMI) ≥30 kg/m2 or ≥28 kg/m2 in the presence of other risk factors (diabetes mellitus, hypertension, dyslipidemia). (BMI calculation: BMI = M/P2, where M is body weight, kg; P is height, m.)
Contraindications
- hypersensitivity to orlistat or other components of the drug;
- malabsorption syndrome;
- cholestasis;
- simultaneous use with cyclosporine;
- pregnancy and breastfeeding;
- age up to 18 years.
With caution: a history of hyperoxaluria, nephrolithiasis (calcium oxalate stones).
Application of Orlistat-akrikhin 120 mg 42 pcs. Polpharma capsules Akrikhin during pregnancy and breastfeeding
Orlistat is contraindicated for use during pregnancy due to the lack of reliable clinical data confirming the safety of its use.
It has not been established whether orlistat passes into breast milk, and therefore the use of Xenalten® during breastfeeding is not recommended.
special instructions
During the treatment period, it is necessary to follow a balanced, low-calorie diet containing no more than 30% of calories in the form of fats and enriched with fruits and vegetables.
Before prescribing orlistat, an organic cause of obesity, such as hypothyroidism, should be excluded.
The likelihood of developing side effects from the gastrointestinal tract increases with high fat content in food (more than 30% of daily calories). The daily intake of fats, carbohydrates and proteins should be distributed between three main meals. Because orlistat reduces the absorption of some fat-soluble vitamins, patients should take a multivitamin containing fat-soluble vitamins to ensure adequate intake. In addition, vitamin D and beta-carotene levels may be lower in obese patients than in non-obese individuals. Multivitamins should be taken 2 hours before or 2 hours after taking orlistat, for example at bedtime. In patients who did not receive prophylactic vitamin supplements, a decrease in plasma vitamin levels was recorded at two or more consecutive visits to the doctor during the first and second years of treatment with orlistat. Since the absorption of vitamin K may be reduced when taking orlistat, blood coagulation parameters should be monitored in patients receiving orlistat during long-term chronic use of warfarin.
Taking orlistat in doses exceeding 120 mg 3 times a day does not provide additional effect.
If concomitant use of orlistat with cyclosporine cannot be avoided, continuous monitoring of cyclosporine plasma levels is necessary.
In some patients, urinary oxalate levels may increase with orlistat. As with other weight loss medications, orlistat may be abused in some groups of patients (such as anorexia nervosa or bulimia).
The induction of weight loss by orlistat may be combined with improved metabolic control of diabetes mellitus, which will require a reduction in doses of oral hypoglycemic agents (sulfonylureas, metformin) or insulin. If after 12 weeks of therapy with Xenalten® the decrease in body weight is less than 5% of the initial value, a doctor’s consultation is necessary to decide whether to continue treatment with orlistat.
Treatment should not last more than 2 years.
Xenalten® is not intended for use in pediatric practice.
Impact on the ability to drive vehicles and maintain moving mechanisms. Does not affect the ability to drive vehicles and maintain moving machinery.
Overdose
Cases of overdose have not been described.
A single dose of 800 mg of orlistat or multiple doses of up to 400 mg 3 times a day for 15 days by people with normal body weight and obesity were not accompanied by significant side effects.
If a significant overdose of orlistat is detected, the patient's condition should be monitored for 24 hours. Based on studies in animals and humans, systemic effects associated with the lipase inhibitory properties of orlistat should be quickly reversible.
Side effects Orlistat-akrikhin 120 mg 42 pcs. Polpharma capsules Akrikhin
The frequency of the adverse reactions listed below was determined according to the following: very often (>1/10); often (>1/100.1/1000.1/10000,
From the gastrointestinal tract: very often - oily discharge from the rectum, release of gases with some discharge, imperative urge to defecate, steatorrhea, increased frequency of bowel movements, loose stools, flatulence, pain or discomfort in the abdomen.
As a rule, these adverse reactions are mild and transient and occur in the early stages of treatment (in the first 3 months). The incidence of these adverse reactions increases with increasing dietary fat content. Patients should be informed about the possibility of these adverse reactions and taught how to eliminate them through better diet, especially regarding the amount of fat contained in it. Often - soft stools, pain or discomfort in the rectum, fecal incontinence, bloating, dental damage, gum damage.
From the respiratory system, chest and mediastinal organs: very often - upper respiratory tract infections, often - lower respiratory tract infections.
From the immune system: rarely - itching, urticaria, rash, angioedema, bronchospasm, anaphylaxis.
From the nervous system: very often - headaches.
From the liver and biliary tract: very rarely - increased activity of transaminases and alkaline phosphatase, hepatitis.
From the kidneys and urinary tract: often - urinary tract infections.
Other: very often - influenza; often - dysmenorrhea, anxiety, weakness.
If any of the side effects indicated in the instructions worsen or any other side effects not listed in the instructions are noticed, you should inform your doctor.
Drug interactions
Orlistat does not affect the pharmacokinetics of ethanol, digoxin (prescribed in a single dose) and phenytoin (prescribed in a single dose of 300 mg), or the bioavailability of nifedipine (extended-release tablets). Ethanol does not affect the pharmacodynamics (fat excretion) and systemic exposure of orlistat.
With the simultaneous use of orlistat and cyclosporine, the level of the latter in plasma decreases (orlistat and cyclosporine should not be taken simultaneously; to reduce the likelihood of drug interactions, cyclosporine should be taken 2 hours before or 2 hours after taking orlistat).
With the simultaneous use of warfarin or other indirect anticoagulants with orlistat, prothrombin levels may decrease and the INR value may change, so INR monitoring is necessary. Orlistat reduces the absorption of beta-carotene from dietary supplements by 30% and inhibits the absorption of vitamin E (in the form of tocopherol acetate) by approximately 60%.
Increases the bioavailability and lipid-lowering effect of pravastatin, increasing its plasma concentration by 30%.
When taken simultaneously with orlistat, the absorption of vitamins A, D, E and K is reduced. If multivitamins are recommended, they should be taken at least 2 hours after taking Xenalten® or before bedtime.
Losing body weight can improve metabolism in patients with diabetes, as a result of which it is necessary to reduce the dose of oral hypoglycemic drugs.
Concomitant use with acarbose is not recommended due to the lack of data on pharmacokinetic interactions. When used simultaneously with orlistat, a decrease in plasma amiodarone levels was observed after a single dose. The simultaneous use of orlistat and amiodarone is possible only on the recommendation of a doctor.
Orlistat may indirectly reduce the bioavailability of oral contraceptives, which may lead to the development of unwanted pregnancy. It is recommended to use additional types of contraception if acute diarrhea develops.
Clinically significant interactions with digoxin, amitriptyline, phenytoin, fluoxetine, sibutramine, atorvastatin, pravastatin, losartan, glibenclamide, oral contraceptives, nifedipine, furosemide, captopril, atenolol and ethanol were not observed.
Orlistat-Akrikhin, 120 mg, capsules, 42 pcs.
Diet and exercise are an integral part of a weight loss program. It is recommended to begin a dietary program and exercise before starting therapy with Orlistat-Akrikhin. While taking the drug Orlistat-Akrikhin, you must adhere to a fractional, balanced, moderately hypocaloric diet, with a fat content of no more than 30% of the daily calorie intake (for example, with a diet of 2000 kcal/day, fat intake should be no more than 66 g/day). You should adhere to the recommendations received regarding diet and physical activity, both during and after stopping the drug. The use of the drug Orlistat-Akrikhin leads to an increase in fat content in feces already 24-48 hours after the start of administration. After discontinuation of the drug Orlistat-Akrikhin, the fat content in the stool usually returns to its original level within 48-72 hours. Following a low-fat diet reduces the likelihood of adverse reactions from the gastrointestinal tract. Taking orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E, K and beta-carotene). The vast majority of patients receiving orlistat during the four-year clinical studies had vitamin A, D, E, K and beta-carotene concentrations within normal limits. For preventive purposes, it is recommended to take multivitamins at night. Since weight loss is usually accompanied by an improvement in carbohydrate metabolism, patients with type 2 diabetes mellitus should consult a doctor before starting therapy with Orlistat Akrikhin and, if necessary, adjust the dose of hypoglycemic drugs. A decrease in body weight during treatment may be accompanied by a decrease in blood pressure and the concentration of TC in the blood plasma. Patients taking antihypertensive or lipid-lowering drugs should consult a doctor and, if necessary, adjust the dose of these drugs. In clinical studies, no interaction was observed between oral contraceptives and orlistat. However, orlistat may indirectly reduce the bioavailability of oral contraceptives, which may lead to the development of unwanted pregnancy. It is recommended to use additional methods of contraception in case of acute diarrhea. Patients with kidney disease should consult a doctor, as hyperoxaluria and nephropathy may develop. Patients taking amiodarone, warfarin or other oral anticoagulants should also consult a physician before starting orlistat therapy as changes in the INR may occur. Patients should stop taking Orlistat-Akrikhin and consult a doctor if symptoms appear: icteric discoloration of the sclera or skin, itching, dark urine and loss of appetite. Cases of rectal bleeding have been observed with the use of orlistat. If this phenomenon occurs, the patient should consult a doctor. When orlistat and levothyroxine sodium are used together, hypothyroidism and/or decreased control of hypothyroidism may develop. Patients taking levothyroxine sodium should consult their doctor before starting treatment with orlistat, because It may be necessary to take orlistat and levothyroxine sodium at different times, and the dose of levothyroxine sodium may need to be adjusted. Patients taking antiepileptic drugs should consult their doctor before starting treatment with orlistat, because they should be monitored for possible changes in the frequency and severity of seizures. In these cases, the possibility of taking orlistat and antiepileptic drugs at different times should be considered. Patients should consult their physician before using orlistat concomitantly with antiretroviral drugs used to treat HIV infection. Orlistat-Akrikhin may reduce the absorption of antiretroviral drugs and negatively affect their effectiveness.
