Instructions for use XENICAL
In long-term clinical studies, in the majority of patients, the concentrations of vitamins A, D, E, K and beta-carotene remained within normal limits during drug therapy for up to 4 years. To ensure adequate nutrition, multivitamin supplements should be considered.
Patients should be advised to adhere to a diet.
The likelihood of adverse reactions from the gastrointestinal tract may increase if Xenical is taken on a diet rich in fat (for example, with a calorie content of 2000 kcal/day, of which more than 30% is in the form of fat, which is equivalent to more than 67 g of fat). Daily fat intake should be divided into three main meals. If Xenical is taken with any meal very rich in fat, the likelihood of gastrointestinal reactions increases.
The decrease in body weight caused by taking the drug Xenical is accompanied by an improvement in the regulation of carbohydrate metabolism in patients with type 2 diabetes mellitus, which may allow or necessitate a reduction in the dose of hypoglycemic drugs (for example, sulfonylurea derivatives).
During post-marketing safety monitoring, isolated cases of severe liver dysfunction were identified with the use of orlistat. Currently, a cause-and-effect relationship between the use of orlistat and the development of severe liver dysfunction has not been established. However, if you suspect liver dysfunction (anorexia, itching, jaundice, dark urine, light stool, pain in the right hypochondrium), you should immediately stop taking orlistat and check the level of liver enzymes (ALT, AST) and other indicators of liver function.
Clinical studies of the drug in patients with renal and/or liver failure have not been conducted.
Use in pediatrics
Clinical studies of the drug in children under 12 years of age have not been conducted.
Efficacy/Clinical Studies
Obese adults
Clinical studies have shown that the use of orlistat promotes weight loss, exceeding the results obtained with diet alone. Weight loss became noticeable within 2 weeks of starting therapy and continued for 6 to 12 months, even in those who did not achieve positive results with diet alone. Statistically significant improvements in metabolic risk factors associated with obesity were observed over 2 years.
Orlistat also turned out to be an effective drug for preventing re-gain of body weight, while in only about half of the patients the increase in body weight did not exceed 25% of its decrease, and in the other half of the patients the body weight no longer increased or even continued to decrease.
Patients suffering from obesity and type 2 diabetes mellitus
Clinical trials conducted over 6 months showed that the use of the drug in patients suffering from obesity and type 2 diabetes mellitus promotes greater weight loss than the use of diet alone. It was also found that the reduction in body weight was primarily due to a decrease in body fat. In addition, despite taking antidiabetic medications, patients generally had poor glycemic control prior to study participation, but after initiation of orlistat therapy, glycemic control showed statistically significant (and clinically important) improvements. In addition, the use of hypoglycemic drugs was reduced, insulin levels decreased, and a decrease in insulin resistance was observed.
Delay in onset of type 2 diabetes mellitus in obese patients
A clinical trial conducted over 4 months showed that orlistat significantly reduced the risk of type 2 diabetes in obese patients, with the risk reduced by almost 37% compared with the placebo group. The risk reduction in patients who initially suffered from a disorder in the mechanism of glucose uptake was even more significant and amounted to 45%. In addition, weight loss in the orlistat group was much greater than in the placebo group and was maintained throughout the 4-year study period. In addition, patients taking orlistat had a significant reduction in the number of metabolic risk factors compared to patients taking placebo.
Obese teenagers
A 1-year clinical trial showed a decrease in body mass index in obese adolescents treated with orlistat compared with adolescents in the placebo group, whose body mass index increased. Moreover, adolescents taking orlistat showed significant reductions in body fat and waist and hip circumference compared to adolescents in the placebo group. Diastolic blood pressure was also significantly lower in adolescents taking orlistat.
Xenical®
Clinical trial data
The following categories are used to describe the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000 , <1/1000) and very rarely (<1/10000), including isolated cases.
Adverse reactions to orlistat occurred mainly from the gastrointestinal tract and were due to the pharmacological effect of the drug, which interferes with the absorption of dietary fats. The incidence of adverse events decreased with long-term use of orlistat.
The following adverse events occurred with an incidence of >2% and an incidence of ≥1% compared with placebo.
Infectious and parasitic diseases:
very often - influenza.
Metabolic disorders:
very often - hypoglycemia*.
Mental disorders:
often - anxiety.
Nervous system disorders
: very often - headache.
Disorders of the respiratory system, chest and mediastinal organs:
very often - upper respiratory tract infection; often - lower respiratory tract infection.
Gastrointestinal disorders:
very often - pain or discomfort in the abdomen, oily discharge from the rectum, release of gases with some discharge, urgency to defecate, steatorrhea, flatulence, loose stools, increased frequency of bowel movements; often - pain or discomfort in the rectum, “soft” stools, fecal incontinence, dental damage, gum damage, bloating*.
Renal and urinary tract disorders
: often - urinary tract infections.
Genital and breast disorders
: often - irregular menstruation.
General and administration site disorders
: often - weakness.
In patients with type 2 diabetes mellitus, the nature and frequency of adverse events were comparable to those in overweight and obese individuals without diabetes mellitus.
*The only new adverse events in obese patients with type 2 diabetes were hypoglycemic conditions (very common) and abdominal bloating (common), occurring at an incidence of >2% and an incidence of ≥1% compared with placebo.
The incidence of gastrointestinal disorders increases with increasing dietary fat content. Patients should be informed of the possibility of gastrointestinal adverse reactions and taught how to manage them through better dietary management, especially regarding the amount of fat contained in the diet. Adopting a low-fat diet reduces the likelihood of gastrointestinal side effects and thereby helps patients control and regulate their fat intake.
As a rule, these adverse reactions are mild and transient. They occurred in the early stages of treatment (in the first 3 months), and most patients had no more than one episode of such reactions.
In the 4-year clinical study, the overall safety profile did not differ from that obtained in the 1- and 2-year studies. At the same time, the overall incidence of adverse events from the gastrointestinal tract decreased annually over the 4-year period of taking the drug.
Post-marketing surveillance
The adverse events listed below were identified in spontaneous post-marketing reports, the frequency of development is unknown.
Immune system disorders:
hypersensitivity reactions, the main clinical symptoms of which were itching, rash, urticaria, angioedema, bronchospasm and anaphylaxis.
Gastrointestinal disorders:
rectal bleeding, diverticulitis, pancreatitis.
Disorders of the liver and biliary tract:
cholelithiasis, isolated, possibly serious, cases of liver damage leading to liver transplantation or death.
Skin and subcutaneous tissue disorders
: bullous rash.
Renal and urinary tract disorders
: oxalate nephropathy, which can sometimes lead to kidney failure.
Laboratory abnormalities:
increased activity of “liver” transaminases and alkaline phosphatase, decreased prothrombin concentrations, increased international normalized ratio (INR) values and cases of unbalanced anticoagulant therapy, which led to changes in hemostatic parameters (see section “Interaction with other drugs”).
When taking orlistat and antiepileptic drugs simultaneously, cases of seizures have been observed (see section “Interaction with other drugs”).
Cases of hyperoxaluria have been reported.
Xenical, 42 pcs., 120 mg, capsules
The following categories are used to describe the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000 , <1/1000) and very rarely (<1/10000), including isolated cases.
Adverse reactions to orlistat occurred mainly from the gastrointestinal tract and were due to the pharmacological effect of the drug, which interferes with the absorption of dietary fats. Very often, phenomena such as oily discharge from the rectum, the release of gases with some discharge, an imperative urge to defecate, steatorrhea, increased frequency of bowel movements, loose stools, flatulence, pain or discomfort in the abdomen were noted.
Their frequency increases with increasing fat content in food. Patients should be informed of the possibility of gastrointestinal adverse reactions and taught how to manage them through better diet, especially regarding the amount of fat contained in the diet. Adopting a low-fat diet reduces the likelihood of gastrointestinal side effects and thereby helps patients control and regulate their fat intake.
As a rule, these adverse reactions are mild and transient. They occurred in the early stages of treatment (in the first 3 months), and most patients had no more than one episode of such reactions.
When treated with Xenical, the following adverse events from the gastrointestinal tract often occur: “soft” stools, pain or discomfort in the rectum, fecal incontinence, bloating, dental damage, gum damage.
Also noted very often were headaches, upper respiratory tract infections, flu; often - lower respiratory tract infections, urinary tract infections, dysmenorrhea, anxiety, weakness.
Rare cases of allergic reactions have been described, the main clinical symptoms of which were itching, rash, urticaria, angioedema, bronchospasm and anaphylaxis.
Very rare cases of bullous rash, increased activity of transaminases and alkaline phosphatase, as well as isolated, possibly serious cases of hepatitis have been described (a cause-and-effect relationship with taking Xenical or pathophysiological mechanisms of development have not been established).
With the simultaneous administration of Xenical and anticoagulants, cases of decreased prothrombin and increased INR have been reported.
Cases of rectal bleeding, diverticulitis, pancreatitis and cholelithiasis have been reported (incidence unknown).
In patients with type 2 diabetes mellitus, the nature and frequency of adverse events were comparable to those in individuals without diabetes mellitus with overweight and obesity. The only new adverse effects occurring at an incidence of >2% and ≥1% compared with placebo were hypoglycemic conditions (which may have resulted from improved carbohydrate compensation) and abdominal bloating.
