Saxenda solution for subcutaneous injection 6mg/ml syringe cartridge 3ml, 5pcs

Composition

Solution for subcutaneous use.

1 ml of the drug contains:

Active ingredient:

liraglutide 6 mg (one pre-filled syringe pen contains 3 ml of solution, which corresponds to 18 mg of liraglutide);

excipients:

sodium hydrophosphate dihydrate 1.42 mg,

phenol 5.5 mg,

propylene glycol 14.0 mg;

hydrochloric acid/sodium hydroxide (for pH correction),

water for injection up to 1 ml

Pharmacological action

Pharmacotherapy group

Hypoglycemic agent – glucagon-like polypeptide receptor agonist.

ATX code A10BX07.

Pharmacological properties

Mechanism of action

The Active ingredient of the drug Saxenda® – liraglutide-is an analog of human glucagon-like peptide-1 (GLP-1), produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain, which has 97% homology of the amino acid sequence to endogenous human GLP-1. Liraglutide binds and activates the GLP-1 receptor (GLP-1 P).

Liraglutide is resistant to metabolic degradation, its plasma half-life after subcutaneous use is 13 hours. The pharmacokinetic profile of liraglutide, which allows it to be administered to patients once a day, is the result of self-association, which results in delayed absorption of the drug; binding to plasma proteins; and resistance to dipeptidyl peptidase-4 (DPP-4) and neutral endopeptidase (NEP).

GLP-1 is a physiological regulator of appetite and food intake. GLP-1R is found in several brain regions involved in regulating appetite. In animal studies, use of liraglutide led to its uptake in specific areas of the brain, including the hypothalamus, where liraglutide, through specific activation of GLP-1p, increased satiety signals and weakened hunger signals, thereby leading to a decrease in body weight.

Liraglutide reduces body weight in humans mainly by reducing the mass of adipose tissue. Weight loss occurs by reducing food intake. Liraglutide does not increase 24-hour energy consumption. Liraglutide regulates appetite by enhancing the feeling of fullness and satiety in the stomach, while simultaneously reducing hunger and reducing the intended food intake.

Liraglutide stimulates insulin secretion and reduces unnecessarily high glucagon secretion in a glucose-dependent manner, and also improves the function of pancreatic beta cells, which leads to a decrease in fasting and post-meal glucose concentrations. The mechanism of lowering glucose concentration also involves a slight delay in gastric emptying.

Pharmacodynamics

In long-term clinical trials involving overweight or obese patients, the use of Saxenda® in combination with a low-calorie diet and increased physical activity resulted in significant weight loss.

Effects on appetite, calorie intake, energy expenditure, gastric emptying, and fasting and postprandial glucose concentrations

The pharmacodynamic effects of liraglutide were studied in a five-week study involving 49 obese patients (body mass index (BMI) 30-40 kg/m2) without diabetes mellitus.

Appetite, calorie intake, and energy expenditure

It is believed that weight loss with the use of Saxenda® is associated with the regulation of appetite and the number of calories consumed. Appetite was evaluated before and for 5 hours after a standard breakfast; unlimited food intake was evaluated during a subsequent lunch. Saxenda® increased the feeling of fullness and fullness of the stomach after eating and reduced hunger and the estimated amount of estimated food intake, as well as reduced unlimited food intake compared to placebo. No therapy-related increase in 24-hour energy expenditure was observed when evaluated using a respiratory camera.

Emptying the stomach

The use of Saxenda® resulted in a slight delay in gastric emptying during the first hour after eating, as a result of which the rate of concentration increase decreased, as well as the total concentration of blood glucose after eating.

Fasting and postprandial glucose, insulin, and glucagon concentrations

Fasting and postprandial glucose, insulin, and glucagon concentrations were evaluated before and within 5 hours of a standardized meal. Compared to placebo, Saxenda® reduced fasting and postprandial blood glucose concentrations (AUC0-60 min) within the first hour after ingestion, as well as reduced 5-hour glucose AUC and increasing glucose concentration (AUC0-300 min). In addition, Saxenda reduced postprandial glucagon (AUC0-300 min) and insulin (AUC0-60 min) concentrations and increased postprandial insulin concentrations (iAUC0-60 min) compared to placebo.

Fasting and increasing glucose and insulin concentrations were also evaluated during an oral glucose tolerance test (PTHT) with 75 g of glucose before and after 1 year of therapy in 3,731 obese patients with and without impaired glucose tolerance. Compared to placebo, Saxenda® reduced fasting concentrations and increased glucose concentrations. The effect was more pronounced in patients with impaired glucose tolerance. In addition, Saxenda reduced fasting concentrations and increased the cumulative insulin concentration compared to placebo.

Effect on fasting and increasing glucose concentrations in overweight or obese patients with type 2 diabetes mellitus

Saxenda reduced the fasting glucose concentration and the average increasing postprandial glucose concentration (90 minutes after a meal, the average value for 3 meals per day) compared to placebo.

The function of the beta cells of the pancreas acid

In clinical trials lasting up to one year with Saxenda® in overweight or obese patients and with or without diabetes mellitus, improvement and maintenance of pancreatic beta cell function were demonstrated using measurement methods such as the homeostatic beta cell Function Assessment model (HOMA-B) and the ratio of proinsulin to insulin concentrations.

Clinical efficacy and safety

The efficacy and safety of using Saxenda® for long-term weight correction in combination with a low-calorie diet and increased physical activity was studied in 4 randomized double-blind placebo-controlled studies (3 studies lasting 56 weeks and 1 study lasting 32 weeks). The study included a total of 5,358 patients from 4 different populations: 1) obese or overweight patients, as well as with one of the following conditions/diseases: impaired glucose tolerance, arterial hypertension, dyslipidemia; 2) obese or overweight patients with insufficiently controlled type 2 diabetes mellitus (HbA1c value in the range of 7-10%), before the study, diet and exercise, metformin, sulfonylureas, glitazone alone or in any combination were used to correct HbA1c in these patients. 3) obese patients with moderate or severe obstructive sleep apnea; 4) obese or overweight patients with concomitant arterial hypertension or dyslipidemia who achieved a weight loss of at least 5% using a low-calorie diet.

Body weight

More pronounced weight loss was achieved in obese/ overweight patients treated with Saxenda® compared to placebo-treated patients in all study groups, including those with or without impaired glucose tolerance, type 2 diabetes mellitus, and moderate or severe obstructive sleep apnea. In study 1 (obese and overweight patients with or without impaired glucose tolerance), weight loss was 8.0% in patients treated with Saxenda®, compared with 2.6% in the placebo group. In study 2 (obese and overweight patients with type 2 diabetes mellitus), weight loss was 5.9% in patients treated with Saxenda®, compared with 2.0% in the placebo group. In study 3 (obese and overweight patients with moderate or severe obstructive sleep apnea), the weight loss was 5.7% in patients treated with Saxenda®, compared to 1.6% in the placebo group. In study 4 (obese and overweight patients after a previous weight loss of at least 5%), further weight loss was 6.3% in patients treated with Saxenda®, compared with 0.2% in the placebo group. In study 4, a larger number of patients maintained the weight loss that was achieved before starting treatment with Saxenda® compared to placebo (81.4% and 48.9%, respectively). In addition, in all populations studied, the majority of patients treated with Saxenda achieved weight loss of at least 5% and more than 10% compared to patients treated with placebo.

In Study 1 (obese and overweight patients with or without impaired glucose tolerance),63.5% of patients treated with Saxenda® experienced a weight loss of at least 5% at week 56 of therapy, compared to 26.6% in the placebo group.The ratio of patients who achieved more than 10% weight loss at week 56 of therapy is 32.8% in the group of patients treated with Saxenda®, compared with 10.1% in the placebo group. Overall, weight loss occurred in approximately 92% of patients treated with Saxenda, compared to approximately 65% in the placebo group.

Weight loss after 12 weeks of therapy with Saxenda®

Patients with an early response to therapy were defined as patients who achieved a weight loss of at least 5% after 12 weeks of therapy (4 weeks of dose increase and 12 weeks of 3 mg therapy).

In two studies (obese or overweight patients without and with type 2 diabetes),67.5% and 50.4% of patients achieved a weight loss of at least 5% after 12 weeks of therapy. With continued treatment with Saxenda® (up to 1 year),86.2% of these patients achieved a weight loss of at least 5% and 51% achieved a weight loss of at least 10%. The average weight loss in these patients who completed the study was 11.2% compared to baseline. In patients who achieved a weight loss of less than 5% after 12 weeks of 3 mg therapy and completed the study (1 year), the average weight loss was 3.8%.

Glycemic control

Treatment with Saxenda significantly improved glycemic parameters in subpopulations with normoglycemia, impaired glucose tolerance (mean decrease in HbA1c-0.3%) and type 2 diabetes mellitus (mean decrease in HbA1c – 1.3%) compared to placebo (mean decrease in HbA1c-0.1% and – 0.4%, respectively). In a study involving patients with impaired glucose tolerance, fewer patients treated with Saxenda developed type 2 diabetes compared to the placebo group (0.2% and 1.1%, respectively). A larger number of patients with impaired glucose tolerance experienced a reverse development of this condition compared to the placebo group (69.2% and 32.7%, respectively).

In a study involving patients with type 2 diabetes mellitus,69.2% and 56.5% of patients treated with Saxenda ® achieved the target HbA1c value of 7% and ≤ 6.5%, respectively, compared to 27.2% and 15.0% in patients treated with placebo.

Cardiometabolic parameters

In a study involving obese or overweight patients with or without impaired glucose tolerance, Saxenda® showed a significant decrease in systolic blood pressure (4.3 points vs. 1.5 points), diastolic blood pressure (2.7 points vs. 1.8 points), waist circumference (8.2 cm vs. 4.0 cm) and a significant change in fasting lipid concentrations (3.2% vs. 0.9% decrease in total cholesterol; 3.1% vs. 0.7% decrease in low-density lipoproteins; an increase in high-density lipoproteins by 2.3% vs. 0.5%; reduced triglycerides by 13.6% vs. 4.8%) compared to placebo.

Apnea-Hypnosis Index

When using Saxenda®, there was a significant reduction in the severity of obstructive sleep apnea compared to placebo, which was assessed by a decrease in the apnea-hypnosis index (AH) by 12.2 cases per hour and 6.1 cases per hour, respectively.

Immunogenicity

Given the potential immunogenic properties of protein and peptide drugs, patients may develop antibodies to liraglutide after treatment with Saxenda®. In clinical trials,2.5% of patients treated with Saxenda® developed antibodies to liraglutide. The formation of antibodies did not reduce the effectiveness of Saxenda®.

Assessment of cardiovascular events

Significant adverse cardiovascular events (MACE) were evaluated by a group of external independent experts and defined as non-fatal myocardial infarction, non-fatal stroke, and death due to cardiovascular pathology. In all long-term clinical trials using Saxenda®,6 MACE were observed in patients receiving Saxenda® and 10 MACE in patients receiving placebo. The risk ratio and 95% CI when comparing Saxenda and placebo was 0.31 [0.10; 0.92]. In phase 3 clinical trials, an increase in heart rate (HR) of an average of 2.5 beats per minute (1.6 to 3.6 beats per minute in selected studies) was observed in patients treated with Saxenda®. The greatest increase in heart rate was observed after 6 weeks of therapy. This increase was reversible and disappeared after discontinuation of liraglutide therapy.

Patient evaluation results

Saxenda® compared with placebo improved patient-defined scores on individual indicators. There was a significant improvement in the overall assessment of the Simplified Questionnaire of the influence of body weight on quality of life (IWQoL-Lite) and on all scales of the SF-36 quality of life questionnaire, which indicates a positive impact on the physical and psychological components of quality of life.

Preclinical safety data sheet

Preclinical data based on studies of pharmacological safety, repeated dose toxicity and genotoxicity did not reveal any danger to humans.

In two-year carcinogenicity studies in rats and mice, thyroid C-cell tumors were identified that did not lead to a fatal outcome. The non-toxic dose (NOAEL) in rats has not been established. Monkeys treated for 20 months did not develop these tumors. The results obtained in rodent studies are due to the fact that rodents are particularly sensitive to a non‑genotoxic specific mechanism mediated by the GLP-1 receptor. The significance of the data obtained for humans is low, but cannot be completely excluded. The appearance of other neoplasms associated with the therapy was not noted.

In animal studies, there was no direct adverse effect of the drug on fertility, but there was a slight increase in the frequency of early fetal death with the use of the highest doses of the drug. The introduction of liraglutide in the middle of the gestational period caused a decrease in the mother’s body weight and fetal growth with an unknown effect on the ribs in rats, and in rabbits – deviations in the structure of the skeleton. Neonatal growth was reduced in rats during liraglutide therapy, and this decrease persisted after the end of breastfeeding in the high-dose group. It is not known whether this decrease in the growth of newborn rats is due to a decrease in caloric intake by maternal individuals or a direct effect of GLP-1 on the fetus / newborns.

Pharmacokinetics

Suction

Absorption of liraglutide after subcutaneous use is slow, the time to reach the maximum concentration (tmax) is about 11 hours after use. In obese patients (BMI 30-40 kg / m2) after use of liraglutide at a dose of 3 mg, the average steady-state concentration of liraglutide (AUCt/24) reaches approximately 31 nmol/l. In the dose range from 0.6 mg to 3 mg, liraglutide exposure increases in proportion to the dose. The absolute bioavailability of liraglutide after subcutaneous use is approximately 55%.

Distribution

The average apparent volume of distribution after subcutaneous use of liraglutide at a dose of 3 mg is 20-25 liters (in individuals with a body weight of about 100 kg). Liraglutide binds significantly to plasma proteins (> 98%).

Metabolism

During 24 hours after use of a single dose of [3H]‑liraglutide to healthy volunteers, the main component in plasma remained unchanged liraglutide. Two metabolites were detected (≤ 9% and ≤ 5% of total plasma radioactivity).

Deduction

Liraglutide is metabolized endogenously like large proteins without the involvement of any specific organ as the main route of elimination. After use of a dose of [3H]-liraglutide, unchanged liraglutide was not detected in the urine or feces. Only a small part of the administered radioactivity in the form of liraglutide metabolites was eliminated by the kidneys or through the intestine (6% and 5%, respectively). Radioactive substances are excreted by the kidneys or through the intestines, mainly during the first 6-8 days and represent 3 metabolites.

The average clearance after subcutaneous use of liraglutide is approximately 0.9-1.4 l / h, with a half-life of approximately 13 hours.

Special patient groups

Elderly patients

No age-appropriate dose adjustment is required. According to the results of a population pharmacokinetic analysis in obese or overweight patients aged 18-82 years, age did not have a clinically significant effect on the pharmacokinetics of liraglutide when administered subcutaneously at a dose of 3 mg.

Gender

Based on population pharmacokinetic analysis, the body weight-adjusted clearance of liraglutide after subcutaneous use of 3 mg is 24% lower in women than in men. Based on data on the response to drug exposure, no gender-specific dose adjustment is required.

Ethnicity

According to the results of a population pharmacokinetic analysis, which included data from studies in obese or overweight patients of Caucasian, Black, Asian and Latin American racial groups, ethnicity did not have a clinically significant effect on the pharmacokinetics of liraglutide when administered subcutaneously at a dose of 3 mg.

Body weight

Liraglutide exposure decreases with increasing initial body weight.The use of liraglutide at a dose of 3 mg daily provides adequate exposure in the body weight range of 60-234 kg, according to the assessment of the response to systemic exposure of the drug in clinical studies. Liraglutide exposure in patients weighing more than 234 kg was not studied.

Patients with hepatic impairment

The pharmacokinetics of liraglutide were evaluated in patients with varying degrees of hepatic impairment in a single dose study (0.75 mg). Liraglutide exposure was 23% and 13% lower in patients with mild or moderate hepatic impairment, respectively, compared with healthy volunteers. The exposure was significantly lower (by 44%) in patients with severe hepatic impairment (>9 points according to the classification). Child Pugh).

Patients with renal insufficiency

In a single-dose study (0.75 mg), liraglutide exposure was lower in patients with renal insufficiency compared to individuals with normal renal function. Liraglutide exposure was reduced by 33%,14%,27%, and 26%, respectively, in patients with mild (creatinine clearance 50-80 ml/min), moderate (30-50 ml/min), and severe renal insufficiency (

Children

Clinical studies of the efficacy and safety of Saxenda® in children have not been conducted.

Indications

Saxenda® is indicated as an adjunct to a low-calorie diet and increased physical activity for long-term use to correct body weight in adult patients with BMI:

• ≥ 30 kg / m2 (obese) or

• ≥ 27 kg / m2 before

Contraindications

• hypersensitivity to liraglutide or any of the auxiliary components of the drug;

• a history of medullary thyroid cancer, including in the family;

• multiple endocrine neoplasia type 2;

• severe depression, suicidal thoughts or behavior, including in the anamnesis.

It is contraindicated in the following groups of patients and in the following conditions/diseases due to the lack of data on efficacy and safety:

• the impairment of renal function, severe;

• a violation of liver function, severe;

• children up to age 18 years;

• pregnancy and breastfeeding;

• heart failure III-IV functional class (according to the classification of NYHA (new York heart Association));

• concurrent use of other drugs for the correction of body weight;

• concomitant use with insulin;

• secondary obesity on the background of endocrine diseases or disorders, eating behavior, or the background of the use of drugs that can cause weight gain.

Experience with Saxenda® in patients with inflammatory bowel diseases and diabetic gastric paresis is limited. The use of liraglutide in such patients is not recommended, as it is associated with transient adverse reactions from the gastrointestinal tract, including nausea, vomiting and diarrhea.

With caution

In patients with NYHA Class I-II chronic heart failure, mild to moderate hepatic impairment, a history of pancreatitis, and thyroid disease; in patients aged ≥ 75 years.

Side effects

The Saxenda clinical trial program consists of 5 completed clinical trials involving 5,813 obese or overweight patients with at least one overweight-related comorbidity. In general, gastrointestinal disorders were the most frequently reported side effects during therapy with Saxenda® (see the section “Description of individual adverse reactions”).

Description of individual adverse reactions:

Hypoglycemia in patients without type 2 diabetes mellitus

In clinical trials involving overweight or obese patients without type 2 diabetes mellitus treated with Saxenda® in combination with diet and exercise, severe hypoglycemia (requiring third-party care) was not observed. Hypoglycaemic symptoms were reported in 1.6% of patients treated with Saxenda and 1.1% of patients treated with placebo; however, these cases were not confirmed by blood glucose measurements. In most cases, mild hypoglycemia was observed.

Hypoglycemia in patients with type 2 diabetes mellitus

In a clinical study involving overweight or obese patients with type 2 diabetes mellitus treated with Saxenda® in combination with diet and exercise, cases of severe hypoglycemia (requiring third-party care) were observed in 0.7% of patients treated with Saxenda®, and only in patients receiving concomitant therapy with sulfonylureas. Also in this group of patients, confirmed hypoglycemia (glucose concentration < 3.9 mmol / l in combination with symptoms) was observed in 43.6% of patients treated with Saxenda® and 27.3% of patients treated with placebo. Among patients who did not receive a concomitant sulfonylurea preparation, confirmed hypoglycemia was observed in 15.7% of patients receiving Saxenda® and in 7.6% of patients receiving placebo.

Adverse reactions from the gastrointestinal tract

Most gastrointestinal reactions were mild to moderate, transient and, in most cases, did not lead to discontinuation of therapy. Reactions usually occurred in the first weeks of therapy, and their manifestations gradually decreased over several days or weeks with continued therapy.

Patients aged ≥ 65 years may experience more pronounced manifestations of adverse reactions from the gastrointestinal tract during therapy with Saxenda®.

Patients with mild or moderate renal impairment (creatinine clearance ≥ 30 ml / min)may experience more pronounced manifestations of adverse reactions from the gastrointestinal tract during therapy with Saxenda®.

Allergic reactions

There have been several cases of anaphylactic reactions with symptoms such as hypotension, palpitation, shortness of breath, or peripheral edema. Anaphylactic reactions can potentially be life-threatening.

Injection site reactions

Injection site reactions have been reported in patients treated with Saxenda. These reactions were usually mild, transient in nature, and in most cases disappeared with continued therapy.

Tachycardia

In clinical trials, tachycardia was observed in 0.6% of patients treated with Saxenda and 0.1% of patients treated with placebo. Most of the events were mild to moderate in severity. The events were isolated and in most cases resolved with continued therapy with Saxenda®.

Interaction

In vitro drug interaction assessment

Liraglutide has been shown to have very low pharmacokinetic interactions with other active substances due to cytochrome P450 (CYP) metabolism and binding to plasma proteins.

Evaluation of drug interaction in vivo

A slight delay in gastric emptying when using liraglutide may affect the absorption of concomitantly administered oral medications. Interaction studies have not demonstrated any clinically significant slowing of absorption, so no dose adjustment is required.

Interaction studies were performed using liraglutide at a dose of 1.8 mg. The effect on the rate of gastric emptying was the same when using liraglutide at a dose of 1.8 mg and 3 mg (AUC0-300 min of paracetamol). Several patients treated with liraglutide had at least one episode of severe diarrhea. Diarrhea may affect the absorption of concomitantly administered oral medications.

Warfarin and other coumarin derivatives

No interaction studies were conducted. A clinically significant interaction with active substances with low solubility or with a narrow therapeutic index, such as warfarin, cannot be excluded. After starting therapy with Saxenda® in patients receiving warfarin or other coumarin derivatives, more frequent monitoring of the international normalized ratio (INR) is recommended.

Paracetamol (acetaminophen)

Liraglutide did not alter the overall exposure of paracetamol after a single 1000 mg dose. Maximum Concentration (Cmax) paracetamol was reduced by 31% and median tmax increased by 15 minutes. No dose adjustment is required for concomitant use of paracetamol.

Atorvastatin

Liraglutide did not alter the overall exposure of atorvastatin after a single dose of atorvastatin 40 mg.Therefore, dose adjustment of atorvastatin when used in combination with liraglutide is not required. Cmax of atorvastatin was reduced by 38%, and median tmax was increased from 1 h to 3 h with liraglutide.

Griseofulvin

Liraglutide did not alter the overall griseofulvin exposure after a single dose of griseofulvin 500 mg. The cmax of griseofulvin was increased by 37%, and the median tmax did not change. Dose adjustment of griseofulvin and other compounds with low solubility and high penetration capacity is not required.

Digoxin

The use of a single dose of digoxin 1 mg in combination with liraglutide resulted in a decrease in the area under the concentration-time curve (AUC) of digoxin by 16%, a decrease in Cmax by 31%. Median tmax increased from 1 h to 1.5 h. Based on these results, no dose adjustment of digoxin is required.

Lisinopril

The use of a single dose of lisinopril 20 mg in combination with liraglutide resulted in a decrease in the AUC of lisinopril by 15%, a decrease in Cmax by 27%. The median tmax of lisinopril increased from 6 hours to 8 hours. Based on these results, no dose adjustment of lisinopril is required.

Oral hormonal contraceptives

Liraglutide reduced the Cmax of ethinyl estradiol and levonorgestrel by 12% and 13%, respectively, after a single dose of an oral hormonal contraceptive. tmax of both drugs against the background of the use of liraglutide increased by 1.5 hours. There was no clinically significant effect on systemic exposure to ethinyl estradiol or levonorgestrel. Thus, no effect on the contraceptive effect is expected when co-administered with liraglutide.

Incompatibility

Medicinal substances added to Saxenda® may cause degradation of liraglutide. Due to the lack of compatibility studies, this medicinal product should not be mixed with other medicinal products.

How to take, course of use and dosage

Method of application

Saxenda® is intended for subcutaneous use only. It should not be administered intravenously or intramuscularly.

The drug Saxenda® is administered once a day at any time, regardless of food intake. It should be administered in the abdomen, hip, or shoulder area. The place and time of injection can be changed without dose adjustment. However, it is advisable to give injections at approximately the same time of day after choosing the most convenient time.

Doses

The initial dose is 0.6 mg per day. The dose is increased to 3 mg per day, adding 0.6 mg at intervals of at least one week to improve gastrointestinal tolerance. If a new dose is not well tolerated by the patient for 2 consecutive weeks when the dose is increased, discontinuation of therapy should be considered. The use of the drug in a daily dose of more than 3 mg is not recommended.

Therapy with Saxenda® should be discontinued if after 12 weeks of using the drug at a dose of 3 mg per day, the loss in body weight was less than 5% of the initial value.

The need to continue therapy should be reviewed annually.

Missed dose

If less than 12 hours have elapsed after the normal dose time, the patient should administer the dose as quickly as possible. If less than 12 hours remain before the usual time for the next dose, the patient should not administer the missed dose, but should resume use of the drug with the next scheduled dose. An additional or increased dose should not be administered to compensate for the missed dose.

Patients with type 2 diabetes mellitus

Saxenda should not be used in combination with other GLP-1 receptor agonists.

At the beginning of therapy with Saxenda®, it is recommended to reduce the dose of concomitant insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycemia.

Special patient groups

Elderly patients (≥ 65 years)

No age-appropriate dose adjustment is required. The experience of using the drug in patients aged ≥ 75 years is limited, and the drug should be used with caution in such patients.

Patients with renal insufficiency

In patients with mild or moderate renal impairment (creatinine clearance ≥ 30 ml/min), no dose adjustment is required. There is limited experience with the use of Saxenda® in patients with severe renal impairment (creatinine clearance The use of Saxenda® in such patients, including patients with end-stage renal failure, is contraindicated.

Patients with impaired liver function

No dose adjustment is required in patients with mild to moderate hepatic impairment. In patients with mild to moderate hepatic impairment, the drug should be used with caution. The use of Saxenda® in patients with severe hepatic impairment is contraindicated.

Children

The use of Saxenda® in children and adolescents under 18 years of age is contraindicated due to the lack of data on safety and efficacy.

Overdose

According to clinical studies and post-marketing use of liraglutide, cases of overdose were reported (a dose of 72 mg was administered, which is 24 times more than the recommended dose for body weight correction).

There was also one case where a six-fold dose (18 mg per day) was administered for 7 months. According to patient reports, these overdoses were accompanied by severe nausea, vomiting and diarrhea, but in all cases the patients recovered without complications. No cases of severe hypoglycemia were reported.

In case of overdose, appropriate symptomatic therapy is necessary.

Special instructions

In patients with diabetes mellitus, Saxenda® should not be used as an insulin substitute.

Cardiovascular insufficiency

There is limited experience in patients with NYHA Class I-II chronic heart failure, so Saxenda® should be used with caution.

Pancreatitis

The use of GLP-1 receptor agonists was associated with the risk of acute pancreatitis. Several cases of acute pancreatitis have been reported with liraglutide. Patients should be informed about the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, the use of Saxenda® should be discontinued; if acute pancreatitis is confirmed, therapy should not be resumed. Caution should be exercised when using the drug in patients with a history of pancreatitis.

Cholelithiasis and cholecystitis

In clinical trials, there was a higher incidence of cholelithiasis and cholecystitis in patients treated with Saxenda® compared to placebo patients. This may be partly explained by the fact that weight loss can increase the risk of developing cholelithiasis and, consequently, cholecystitis. Cholelithiasis and cholecystitis can lead to hospitalization and cholecystectomy. Patients should be informed about the characteristic symptoms of cholelithiasis and cholecystitis.

Thyroid diseases

In clinical studies involving patients with type 2 diabetes mellitus, adverse thyroid events have been reported, including increased serum calcitonin concentrations, goiter, and thyroid neoplasms, especially in patients with pre-existing thyroid diseases. In patients with thyroid disorders, Saxenda® should be used with caution.

In the post-marketing period, cases of medullary thyroid cancer were reported in patients treated with liraglutide. The available data are insufficient to establish or exclude a causal relationship between the occurrence of medullary thyroid cancer and the use of liraglutide in humans. Saxenda® is contraindicated in patients with a history of medullary thyroid cancer, including family history, and multiple endocrine neoplasia type 2. It is necessary to inform the patient about the risk of medullary thyroid cancer and about the symptoms of a thyroid tumor (tightness in the neck, dysphagia, shortness of breath, persistent hoarseness of the voice).

Current monitoring of serum calcitonin concentrations or an ultrasound examination of the thyroid gland is not essential for the early detection of medullary thyroid cancer in patients using Saxenda®. A significant increase in the concentration of calcitonin in the blood serum may indicate the presence of medullary thyroid cancer, patients with medullary thyroid cancer usually have a calcitonin concentration of more than 50 ng/l. If an increase in the concentration of calcitonin in the blood serum is detected, it is necessary to conduct a further examination of the patient. Patients with thyroid nodules detected during a physical examination or ultrasound of the thyroid gland should also be additionally examined.

Your heart rate

In clinical studies, an increase in heart rate was noted. The clinical significance of increased heart rate with Saxenda®, especially in patients with cardiac and cerebrovascular diseases, remains unclear due to limited experience with the drug in these patients. Heart rate should be monitored at intervals consistent with normal clinical practice.Patients should be informed about the symptoms of tachycardia (palpitations or palpitations at rest). In patients with clinically significant persistent tachycardia at rest, therapy with Saxenda should be discontinued.

Dehydration

Signs and symptoms of dehydration, including impaired renal function and acute renal failure, have been reported in patients treated with GLP-1 receptor agonists. Patients receiving Saxenda should be informed about the potential risk of dehydration associated with gastrointestinal side effects and the need to prevent hypovolemia.

Hypoglycemia in overweight or obese patients with

type 2 diabetes mellitus

, the risk of hypoglycemia may be higher in patients with type 2 diabetes mellitus receiving Saxenda® in combination with sulfonylurea derivatives. This risk can be reduced by reducing the dose of a sulfonylurea derivative. The addition of Saxenda to therapy in patients receiving insulin has not been evaluated.

Suicidal thoughts and behavior

In clinical trials,6 (0.2%) of 3384 patients treated with Saxenda reported suicidal thoughts, and one of the patients attempted suicide. This was not observed in patients (1,941 people) who received placebo. Patients should be monitored for the onset or worsening of depression, suicidal thoughts or behaviors, and/or any unexpected changes in mood or behavior. In patients with suicidal thoughts or behaviors, the use of Saxenda® should be discontinued.

It is contraindicated to use Saxenda® in patients with a history of suicidal attempts or active suicidal thoughts.

Breast cancer

In clinical trials, confirmed breast cancer was reported in 14 (0.6%) of 2,379 women treated with Saxenda®, compared to 3 (0.2%) of 1,300 women treated with placebo, including invasive cancer (11 cases in women treated with Saxenda® and 3 cases in women treated with placebo) and in situ intracurrent carcinoma (3 cases in women treated with Saxenda® and 1 case in women treated with placebo). Most cancers were estrogen – and progesterone-dependent. It is not possible to determine whether these cases were associated with the use of Saxenda® due to their too small number. In addition, there is insufficient data to determine whether Saxenda® has an effect on pre – existing breast neoplasms.

Papillary thyroid cancer

In clinical trials, confirmed papillary thyroid carcinoma was reported in 7 (0.2%) of 3,291 patients treated with Saxenda®, compared with no papillary thyroid carcinoma in the placebo group (1,843 patients). Of all cases,4 carcinomas were less than 1 cm in the largest diameter and 4 were diagnosed by histology after a medically indicated thyroidectomy.

Neoplasia of the colon and rectum

In clinical trials, confirmed benign neoplasms of the colon and rectum (mainly colon adenomas) were reported in 17 (0.5%) of 3,291 patients treated with Saxenda®, compared to 4 (0.2%) of 1,843 patients treated with placebo. There were two confirmed cases of colorectal cancer (0.1%) in patients treated with Saxenda® and none in patients treated with placebo.

Cardiac conduction disorders

In clinical trials,11 (0.3%) of 3384 patients treated with Saxenda® reported developing cardiac conduction disorders, such as grade 1 atrioventricular block, right bundle branch block, or left bundle branch block. No cardiac conduction abnormalities were reported in the 1,941 placebo-treated patients.

Fertility

With the exception of a slight decrease in the number of live fetuses, the results of animal studies do not indicate an adverse effect on fertility (see section Preclinical safety data).

Influence on the ability to drive vehicles and mechanisms

The drug Saxenda® does not affect or slightly affects the ability to drive vehicles and mechanisms. Due to the risk of hypoglycemia when using the drug, especially when combined with sulfonylureas in patients with type 2 diabetes, caution should be exercised when driving vehicles and mechanisms.

Form of production

Clear, colorless or almost colorless solution.

Active ingredient

Liraglutide

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection