buy Saxenda online safe and cheap

Description

Description of the medicinal product Saxenda ® (Saxenda)
Based on the official instructions for use of the drug, approved by the manufacturer and prepared for the print edition of the Vidal Handbook 2022.

Marketing Authorization Holder:
NOVO NORDISK, A / S (Denmark)
Contacts for inquiries:
NOVO NORDISK LLC (Russia)
ATX code: A10BJ02 (Liraglutide)
Active substance : liraglutide
Rec.INN registered by WHO
Dosage form
The drug is dispensed by prescription Saxenda ®
Solution for subcutaneous administration of 6 mg / ml: cartridge in a syringe pen 3 ml 3 or 5 pcs.
reg. No: LP-003491 dated 09.03.16 – Current
Re-registration date: 10.03.21
Release form, packaging and composition of Saxenda ®
The solution for subcutaneous administration is transparent, colorless or almost colorless.

1 ml 1 syringe pen
liraglutide 6 mg 18 mg
Excipients : sodium hydrogen phosphate dihydrate, propylene glycol, phenol, sodium hydroxide / hydrochloric acid (for pH correction), water for injection.

3 ml – glass cartridges (1) – plastic multi-dose disposable syringe pens for multiple injections (3) – cardboard packs.
3 ml – glass cartridges (1) – plastic multi-dose disposable syringe pens for multiple injections (5) – cardboard packs.

Clinical and pharmacological group: Hypoglycemic drug. Glucagon-like peptide receptor agonist
Pharmaco-therapeutic group: Hypoglycemic agent – analogue of glucagon-like peptide-1
pharmachologic effect
Pharmacodynamics

The active ingredient of Saxenda ® – liraglutide – is an acylated analogue of human GLP-1, produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain, which has 97% amino acid sequence homology to endogenous human GLP-1. Liraglutide binds and activates the GLP-1 receptor (GLP-1R). Liraglutide is resistant to metabolic degradation, its half-life from plasma after subcutaneous administration is 13 hours. The pharmacokinetic profile of liraglutide, which allows it to be administered to patients 1 time / day, is the result of self-association, as a result of which slow absorption of the drug occurs; binding to plasma proteins; as well as resistance to dipeptidyl peptidase-4 (DPP-4) and neutral endopeptidase (NEP).

GLP-1 is a physiological regulator of appetite and food intake, while GLP-1R is located in several areas of the brain involved in appetite regulation. In animal studies, peripheral administration of liraglutide led to the uptake of the drug in specific areas of the brain, including the hypothalamus, where liraglutide, through specific activation of GLP-1R, increased satiety signals and attenuated hunger signals, thereby leading to a decrease in body weight.

GLP-1R are also present in specific areas of the heart, blood vessels, immune system, and kidneys. In experiments on mice with atherosclerosis, liraglutide prevented the further development of aortic plaques and reduced inflammation in them. In addition, liraglutide had a beneficial effect on plasma lipids. Liraglutide did not reduce the size of pre-existing plaques.

Liraglutide reduces body weight in humans mainly by reducing the mass of adipose tissue. The decrease in body weight occurs by reducing food intake. Liraglutide does not increase 24 hour energy expenditure. Liraglutide regulates appetite by increasing the feeling of fullness and satiety, while reducing hunger and anticipated food intake.

Liraglutide stimulates insulin secretion and reduces unnecessarily high glucagon secretion in a glucose-dependent manner, and also improves pancreatic β-cell function, which leads to a decrease in fasting and postprandial glucose concentration. The mechanism for lowering glucose concentration also includes a slight delay in gastric emptying.

In long-term clinical studies involving patients with overweight and obesity, the use of Saxenda® in combination with a low-calorie diet and increased physical activity led to a significant decrease in body weight.

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

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

Appetite, calorie intake and energy expenditure

It is believed that the decrease in body weight with the use of Saxenda ® is associated with the regulation of appetite and the amount of food consumed. Appetite was assessed before and within 5 hours after a standardized breakfast; unlimited food intake was assessed at the time of the ensuing meal. Compared to placebo , Saxenda® increased the feeling of fullness and fullness after a meal and decreased hunger and estimated food intake, as well as reduced unrestricted food intake. When evaluated with a respirator chamber, there was no therapy-related increase in 24-hour energy expenditure.

Emptying the stomach

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

Fasting and postprandial glucose, insulin and glucagon concentrations

Fasting and postprandial glucose, insulin, and glucagon concentrations were assessed before and within 5 hours after a standardized meal. Compared to placebo, Saxenda® reduced the fasting and postprandial glucose concentration (AUC 0-60 min ) during the first hour after a meal, and also reduced the 5-hour glucose AUC and the increasing glucose concentration (AUC 0-300 min ). In addition, compared with placebo, Saxenda® reduced the postprandial glucagon concentrations (AUC 0-300 min ) and insulin (AUC 0-60 min ) and the increasing insulin concentration (iAUC 0-60 min ) after meals.

Fasting glucose and insulin concentrations and increasing glucose and insulin concentrations were also assessed during an oral glucose tolerance test (OGTT) with 75 g of glucose before the start of therapy and after 1 year of therapy in 3731 overweight and obese patients, as well as with the presence of or no prediabetes. Compared with placebo, Saxenda® reduced fasting concentration and increasing glucose concentration. The effect was more pronounced in patients with prediabetes. In addition, compared with placebo, Saxenda® reduced the fasting insulin concentration and increased the increasing insulin concentration.

After 160 weeks of continued therapy with liraglutide 3.0 mg, plasma glucose AUC decreased, while with placebo it remained unchanged. Additionally, insulin AUC remained relatively stable over the 160-week treatment period with liraglutide 3.0 mg, while a decrease was observed with placebo. All the studied effects of the therapy were statistically significant in favor of liraglutide 3.0 mg.

Effects on fasting glucose concentration and increasing glucose concentration in overweight and obese patients with type 2 diabetes mellitus (T2DM)

Compared with placebo, 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).

Pancreatic β-cell function

Clinical studies lasting up to one year with the use of Saxenda ® in overweight patients, as well as with or without diabetes, have shown an improvement and preservation of the function of pancreatic β-cells. This has been shown using measurement techniques such as the Homeostatic β-Cell Function Assessment Model (HOMA-B) and the ratio of proinsulin to insulin concentrations.

Clinical efficacy and safety

The efficacy and safety of Saxenda ® for long-term body weight correction in combination with a low-calorie diet and increased physical activity was studied in 4 randomized, double-blind, placebo-controlled phase 3 SCALE studies, which included a total of 5358 patients.

Body mass

Compared with placebo, when using Saxenda ® , a more pronounced decrease in body weight was achieved in obese / overweight patients in all studied groups, incl. with or without prediabetes, T2DM, and moderate to severe obstructive sleep apnea. In addition, among the study population, the majority of patients achieved a weight loss of ≥5% and> 10% with Saxenda® compared with placebo. Significant weight loss was also observed in a clinical study in which patients achieved an average weight loss of 6% using a low-calorie diet in the 12 weeks prior to starting Saxenda® treatment …. In this study, more patients retained the weight loss that was achieved before starting treatment with Saxenda® compared with placebo (81.4% and 48.9%, respectively).

Rice. 1. Change in body weight (%) over time compared with the baseline value in patients in study No. 1 (0-56 weeks).

In a clinical study lasting 160 weeks, patients treated with Saxenda® achieved greater weight loss than patients treated with placebo. Basically, weight loss occurred in the first year and was maintained for 160 weeks.

In a clinical study lasting 160 weeks, the mean percent change in body weight and the proportion of patients who achieved at least 5% and more than 10% weight loss from baseline to week 160 were also significant compared to placebo.

Weight loss after 12 weeks of therapy with Saxenda ® (liraglutide 3.0 mg)

In two studies lasting 56 weeks after 12 weeks of therapy with Saxenda® at a dose of 3.0 mg, 67.5% and 50.4% of patients achieved a decrease in body weight of at least 5%. The mean weight loss in these patients who completed the study was 11.2% compared to baseline. In patients who achieved a decrease in body weight of less than 5% after 12 weeks of therapy at a dose of 3.0 mg and completed the study (1 year), the average decrease in body weight was 3.8%.

Glycemic control

Liraglutide therapy significantly improved glycemic parameters in subpopulations with normoglycemia, prediabetes, and T2DM.

T2DM developed in 0.2% of patients treated with Saxenda® , compared with 1.1% in the placebo group. In 69.2% of patients with prediabetes, the reverse development of this condition was observed with the use of Saxenda® , compared with 32.7% in the placebo group . At 160 weeks, with continued treatment, T2DM was diagnosed in 3% of patients receiving Saxenda® and 11% of patients receiving placebo. Compared with placebo, the time to the development of T2DM with the use of liraglutide 3.0 mg was 2.7 times longer, and the relative risk (RR) of developing T2DM with the use of liraglutide was 0.2. At week 160, in the 3.0 mg liraglutide group, 65.9% of patients with prediabetes reversed this condition to normoglycemia, compared with 36.3% in the placebo group.

In one study, 69.2% and 56.5% of obese and T2DM patients treated with Saxenda® achieved target HbA 1c <7% and ≤6.5%, respectively, compared with 27.2% and 15% in patients treated with placebo.

Cardiometabolic parameters

Compared with placebo, Saxenda® significantly improved systolic blood pressure, waist circumference and fasting lipid concentration .

In a clinical study lasting 160 weeks, the average decrease in waist circumference was 8.2 cm with Saxenda® and 4 cm with placebo; the decrease in systolic and diastolic blood pressure was 4.3 mm Hg. and 1.5 mm Hg. when using the drug Saxenda ® and 2.7 mm Hg. and 1.8 mm Hg. when using placebo, respectively; the decrease in the concentration of LDL cholesterol was 3.1 mmol / l when using the drug Saxenda® and 0.7 mmol / l when using placebo; the increase in the concentration of HDL cholesterol was 2.3 mmol / L with the use of Saxenda® and 0.5 mmol / L with the use of placebo.

Apnea-hypnea index (AHI)

Compared with placebo, when using Saxenda® , a significant decrease in the severity of obstructive sleep apnea was observed, which was assessed by the change in AHI relative to the baseline value.

Immunogenicity

Due to the potential immunogenic properties of protein and peptide drugs, patients may develop antibodies to liraglutide after therapy with Saxenda ® . In a clinical study, 2.5% of patients treated with Saxenda® developed antibodies to liraglutide. The formation of antibodies did not lead to a decrease in the effectiveness of Saxenda® .

Evaluation of cardiovascular events

Major cardiovascular events (MCCs) were assessed by a panel of external independent experts and defined as non-fatal myocardial infarction, non-fatal stroke and death due to cardiovascular disease. In 5 double-blind controlled clinical trials of phases 2 and 3 with the use of Saxenda® , 6 BCCS were observed in patients receiving Saxenda® , and 10 BCCS – in patients receiving placebo. The RR with 95% CI was 0.33 with Saxenda® versus placebo. In a phase 3 clinical study, the average increase in heart rate was 2.5 beats / min in patients receiving 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.

A multicenter, placebo-controlled, double-blind clinical study “Effect and exposure of liraglutide in diabetes mellitus: an assessment of cardiovascular risks” (LEADER® ) was carried out .

Compared with placebo, liraglutide 1.8 mg significantly reduced the risk of developing FCCS (Figure 2). The RR for the development of ACCC was consistently below 1 for all three cardiovascular events.

Rice. 2. Kaplan-Meier’s graph – time to the onset of the first BCCS – Complete analysis population (PAP).

Liraglutide 1.8 mg also significantly reduced the risk of developing dilated ACCC (primary ACCC, unstable angina pectoris leading to hospitalization, myocardial revascularization or hospitalization due to heart failure) and other secondary endpoints.

Children and adolescents

In a double-blind clinical study comparing the efficacy and safety of Saxenda® versus placebo for weight loss in obese adolescents 12 years of age and older, Saxenda® was superior to placebo in reducing the standard deviation of BMI (measured to assess weight loss) after 56 weeks of treatment. More patients achieved a ≥5% and ≥10% reduction in BMI on liraglutide therapy than patients on placebo, with more significant reductions in mean BMI and body weight. During 26 weeks of follow-up without the use of the drug, there was a recovery in body weight with the use of Saxenda® compared with placebo (assessed as a change in the standard deviation of BMI).

Based on tolerability, for the majority of patients (82.4%) the dose of the drug was increased and they continued to receive the 3.0 mg dose, for the rest of the patients the dose was increased and they continued to receive the drug in the dose range from 2.4 mg to 0.6 mg.

Patient-Defined Results

Saxenda ® improved patient-defined scores in several ways compared to placebo. There was a significant improvement in the overall score on the Simplified Questionnaire for the Impact of Body Weight on Quality of Life (IWQoL-Lite) and on all scales of the questionnaire for assessing the quality of life SF-36, which indicates a positive effect on the physical and psychological components of the quality of life.

Pharmacokinetics
Suction

Absorption of liraglutide after subcutaneous administration is slow, the time to reach C max is about 11 hours after administration. In obese patients (BMI 30-40 kg / m 2 ) after administration of liraglutide at a dose of 3.0 mg, the average equilibrium concentration of liraglutide (AUC t / 24 ) reaches approximately 31 nmol / l. In the dose range from 0.6 mg to 3.0 mg, the exposure of liraglutide increases in proportion to the dose. The absolute bioavailability of liraglutide after s / c administration is approximately 55%.

Distribution

The average apparent V d after s / c administration of liraglutide at a dose of 3.0 mg is 20-25 L (in persons weighing about 100 kg). Liraglutide binds to a large extent with blood plasma proteins (> 98%).

Metabolism

For 24 hours after the administration of a single dose of [ 3 H] -liraglutide to healthy volunteers, the main component in the plasma remained unchanged liraglutide. Two metabolites were found (≤9% and ≤5% of the total radioactivity level in blood plasma).

Withdrawal

Liraglutide is metabolized endogenously like large proteins without the involvement of any specific organ as the main route of excretion. After administration of a dose of [ 3 H] -liraglutide, unchanged liraglutide was not detected in urine or feces. Only an insignificant part of the introduced radioactivity in the form of liraglutide metabolites was excreted 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 are 3 metabolites.

The average clearance after subcutaneous administration of 3.0 mg of liraglutide is approximately 0.9-1.4 l / h, T 1/2 is approximately 13 hours.

Pharmacokinetics in special patient groups

Elderly patients. No dose adjustment for age is required. According to the results of a population pharmacokinetic analysis in overweight and obese patients aged 18-82 years, age did not have a clinically significant effect on the pharmacokinetics of liraglutide when s / c administration at a dose of 3.0 mg.

Floor. Based on the data of population pharmacokinetic analysis, in women, the body weight-corrected clearance of liraglutide after subcutaneous administration at a dose of 3.0 mg is 24% less than in men. Based on data on response to drug exposure, dose adjustment for gender is not required.

Ethnicity. According to the results of a population pharmacokinetic analysis, which included data from studies in overweight and obese patients of the Caucasian, Negroid, Asian and Hispanic racial groups, ethnicity did not have a clinically significant effect on the pharmacokinetics of liraglutide when administered subcutaneously at a dose of 3.0 mg.

Body mass. The exposure of liraglutide decreases with increasing initial body weight. The use of liraglutide at a dose of 3.0 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 trials. The exposure of liraglutide in patients weighing more than 234 kg has not been studied.

Patients with hepatic impairment. The pharmacokinetics of liraglutide was evaluated in patients with varying degrees of liver dysfunction in a single dose study (0.75 mg). There was a decrease in liraglutide exposure by 13-23% in patients with mild to moderate hepatic insufficiency and a significant decrease in liraglutide exposure (by 44%) in patients with severe hepatic insufficiency (> 9 points according to Child-Pugh classification) in comparison with healthy volunteers.

Patients with renal impairment. In a single dose (0.75 mg) study, liraglutide exposure was lower in patients with renal impairment compared with those with normal renal function. The exposure of liraglutide was less by 33%, 14%, 27% and 26%, respectively, in patients with mild renal insufficiency (CC 50-80 ml / min), moderate (CC 30-50 ml / min), severe (CC <30 ml / min) and in patients with end-stage renal disease requiring hemodialysis.

Children and adolescents. The pharmacokinetic properties of liraglutide 3.0 mg were evaluated in clinical studies in obese adolescents aged 12 to 18 years (134 patients, body weight 62-178 kg). The exposure of liraglutide in adolescents aged 12 to 18 years was comparable to that observed in obese adults.

Pharmacokinetic properties were also evaluated in a clinical pharmacological study involving obese children aged 7 to 11 years (13 patients, body weight 54-87 kg). The exposure of liraglutide 3.0 mg in children aged 7 to 11 years was comparable to that observed in adult patients after adjustment for body weight.

Indications of the drug Saxenda ®
Adults

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

≥30 kg / m2 ( obesity) or
≥27 kg / m2 to <30 kg / m2 ( overweight) with at least one overweight-related comorbidity, such as prediabetes, type 2 diabetes, hypertension, dyslipidemia, or obstructive sleep apnea …
Teenagers

Saxenda ® can be used as a supplement to a healthy diet and increased physical activity in order to correct body weight in adolescents aged 12 years and older with:

body weight over 60 kg and
obese (BMI corresponding to ≥30 kg / m2 for adults according to international thresholds). *
* Threshold BMI IOTF for obesity by gender between ages 12-18.

Table 1. Threshold value of BMI IOTF for obesity by gender, aged 12 to 18 years

Age (number of years) Body mass index 30 kg / m 2
Male gender Female
12 26.02 26.67
12.5 26.43 27.24
thirteen 26.84 27.76
13.5 27.25 28.20
14 27.63 28.57
14.5 27.98 28.87
15 28.30 29.11
15.5 28.60 29.29
sixteen 28.88 29.43
16.5 29.14 29.56
17 29.41 29.69
17.5 29.70 29.84
eighteen 30.00 30.00
Open the list of ICD-10 codes
Dosage regimen
Saxenda ® is intended for subcutaneous administration only. It cannot be administered intravenously or intramuscularly.

Saxenda ® is administered 1 time / day at any time, regardless of food intake. It should be injected into the abdomen, thigh, or shoulder area. The place and time of the injection can be changed without dose adjustment. However, it is advisable to inject at about the same time of day after choosing the most convenient time.

Doses

The initial dose is 0.6 mg / day. The dose is increased to 3.0 mg / day, adding 0.6 mg at intervals of at least one week to improve gastrointestinal tolerance (see table 2). If, with increasing dose, the new dose is poorly tolerated by the patient for 2 consecutive weeks, consideration should be given to discontinuing therapy. The use of the drug in a daily dose of more than 3.0 mg is not recommended.

Table 2. Dose escalation scheme

Dose Weeks
Dose escalation over 4 weeks 0.6 mg one
1.2 mg one
1.8 mg one
2.4 mg one
Therapeutic dose 3.0 mg
Adults. Therapy with Saxenda® should be discontinued if, after 12 weeks of using the drug at a dose of 3.0 mg / day, the body weight loss is less than 5% of the initial value.

Teenagers. Therapy with Saxenda® should be discontinued and reviewed if, after 12 weeks of using the drug at a dose of 3.0 mg / day or the maximum tolerated dose, patients have lost less than 4% of their BMI or BMI z-score.

Patients with type 2 diabetes

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 concurrently used insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycemia. Self-monitoring of blood glucose concentration may be necessary to adjust the dose of insulin or insulin secretagogues.

Special patient groups

No dose adjustment is required in elderly patients (≥65 years) . Experience with the drug in patients ≥75 years of age is limited , and the use of the drug in these patients is not recommended.

In patients with mild or moderate renal insufficiency (CC ≥30 ml / min) , dose adjustment is not required. There is limited experience with the use of Saxenda® in patients with severe renal failure (CC <30 ml / min). The use of Saxenda ® in such patients, including patients with end- stage renal failure , is contraindicated (see sections “Pharmacokinetics” and “Contraindications”).

No dose adjustment is required in patients with mild to moderate hepatic impairment . The use of Saxenda ® in patients with severe hepatic insufficiency is contraindicated. In patients with mild or moderate hepatic impairment , the drug should be used with caution (see the section “Pharmacokinetics” and “Contraindications”).

The use of Saxenda ® in children and adolescents under the age of 12 years or in adolescents weighing ≤60 kg is contraindicated due to lack of data (see section “Pharmacological action”, Clinical efficacy and safety).

For adolescents aged 12 to 18 years , the same dose escalation regimen should be used as for adults (see table 2). The dose of the drug should be increased until a value of 3.0 mg (therapeutic dose) or the maximum tolerated dose is reached. The use of the drug in a daily dose of more than 3.0 mg is not recommended.

Missed dose

If less than 12 hours have elapsed after the usual dosing time, the patient should dose as quickly as possible. If there is less than 12 hours left until the usual time for the next dose, the patient should not enter the missed dose, but should resume the drug from the next scheduled dose. You should not enter an additional or increased dose to compensate for the missed dose.

Application Guide

Do not use Saxenda ® if it looks different from a clear and colorless or almost colorless liquid.

Saxenda ® should not be used if it has been frozen.

Saxenda ® can be administered using needles up to 8 mm long. The pen is designed for use with NovoFine® or NovoTvist® disposable needles . Injection needles are not included in the package.

The patient should be informed that the used needle should be discarded after each injection in accordance with local requirements, and that the Saxenda® syringe pen should be stored with the needle disconnected. Such a measure will prevent clogging of the needles, contamination, infection and leakage of the drug from the syringe pen and guarantees the accuracy of dosing.

Instructions for patients on the use of Saxenda ® solution for subcutaneous administration of 6 mg / ml in a pre-filled syringe pen

Read these instructions carefully before using the pre-filled syringe pen with Saxenda ® .

Use the pen only after you have learned to use it under the guidance of a doctor or nurse.

Start by checking the marking on the pen label to make sure it contains Saxenda ® 6 mg / ml, and then carefully study the illustrations below, which show the various parts of the pen and needle.

If you are visually impaired or you have serious vision problems and you cannot distinguish the numbers on the dose counter, do not use the pen without assistance. A person with good eyesight, trained in the use of a pre-filled syringe pen with Saxenda ® , can help you .

The pre-filled injector pen contains 18 mg of liraglutide and allows you to select doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg. The pen is designed for use with NovoFine® or NovoTvist® disposable needles up to 8 mm long. The needles are not included in the package.

Important information: pay special attention to the information with the sign (!) – this is very important for the safe use of the pen.

Pre-filled syringe pen with Saxenda® and a needle (example)

1. Preparation of a syringe pen with a needle for use

Check the name and color code on the pen label to make sure it contains Saxenda ® . This is especially important if you are using different injectables. Using the wrong drug can be harmful to your health.
Remove the cap from the pen (fig. A).

Make sure that the solution in the pen is clear and colorless (fig. B). Look through the window of the residue scale. If the drug is cloudy, the pen cannot be used.

Take a new needle and remove the protective sticker (fig. C).

Place the needle on the pen and turn it so that the needle is firmly attached to the pen (Fig. D).

Remove the outer needle cap, but do not discard it (fig. E). You will need it after the injection is complete to safely remove the needle from the pen.

Remove and discard the inner needle cap (fig. F). If you try to put the inner cap back on the needle, you could inject yourself. A drop of solution may appear at the end of the needle. This is normal, but you should still check the drug intake if you are using a new pen for the first time. Do not attach a new needle until you are ready to inject.
(!) Always use a new needle for each injection. This can prevent needle sticking, contamination, infection, and misdosing.

(!) Never use a needle if it is bent or damaged.

2. Checking the receipt of the drug

Before the first injection, use each new pen to check the flow of the drug. If the pen is already in use, go to step 3 “Setting the dose”.
Turn the dose selector until the dose counter aligns with the drug delivery check symbol (•• -) (fig. A).

Hold the pen with the needle up. Press the start button and hold it in this position until the dose counter returns to “0” (Fig. B). “0” should be opposite the dose indicator.
A drop of solution should appear at the end of the needle. A small drop may remain at the end of the needle, but it will not be injected when injected.

If a drop of solution does not appear at the end of the needle, it is necessary to repeat operation 2 “Checking the drug supply”, but no more than 6 times. If a drop of solution still does not appear, you should change the needle and repeat step 2 “Checking the drug supply” again.

If a drop of solution still does not appear, discard the pen and use a new one.

(!) Always make sure that a drop of solution appears at the end of the needle before using a new pen for the first time . This ensures that the drug is delivered. If a drop of solution does not appear, the drug will not be injected even if the dose counter moves. This could indicate that the needle is clogged or damaged. If you do not check the flow of the drug before the first injection using a new syringe pen, you may not enter the required dose and the expected effect of Saxenda ® will not be achieved.

3. Setting the dose

Turn the dose selector until it shows the required dose (0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg) (fig. A).
If the dose is not correct, you can turn the dose selector forward or backward until the correct dose is found.

The maximum dose that can be set is 3.0 mg.

The dose selector allows you to change the dose. Only the dose counter and dose indicator will show the amount of mg of the drug in the dose you selected.

You can take up to 3.0 mg of the drug per dose. If the pen contains less than 3.0 mg, the dose counter will stop before 3.0 appears in the window.

With each turn of the dose selector, clicks are heard, the sound of clicks depends on which direction the dose selector rotates (forward, backward, or if the dialed dose exceeds the amount of mg of the drug remaining in the syringe pen). Don’t count these clicks.

(!) Always check before each injection how many mg of the drug you have taken on the dose counter and dose indicator.

Don’t count the clicks of the pen.

The residue scale shows the approximate amount of solution remaining in the pen, so it cannot be used to measure the dose of the drug.

With the dose selector, only the doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg need to be selected. The selected dose must be exactly opposite the dose indicator – this position ensures that you receive the correct dose of the drug.

How much drug is left?

The remainder scale shows the approximate amount of the drug remaining in the syringe pen (Fig. A).

Use the dose counter to determine exactly how much drug is left (Fig. B). Turn the dose selector until the dose counter stops. If it reads “3.0”, there is at least 3.0 mg of the drug left in your pen. If the dose counter stops before “3.0” appears in the window, then there is not enough drug left in the pen to deliver the full 3.0 mg dose.
If you need to inject more of the drug than is left in the syringe pen

Only if you have been trained by a doctor or nurse can you split the dose of the drug between two syringe pens (the one in use and the new one). Use a calculator to plan your doses as recommended by your doctor or nurse.

(!) Be very careful to correctly calculate the dose.

If you are not sure how to properly split the dose using two syringe pens, set and administer the full dose using a new syringe pen.

4. Administration of the drug

Insert the needle under your skin using the injection technique recommended by your doctor or nurse (Figure A).
Make sure the dose counter is in your field of vision. Do not touch the dose counter with your fingers – this may interrupt the injection.

Press the start button all the way and hold it in this position until the dose counter shows “0” (Fig. B). The “0” should be exactly opposite the dose indicator. In doing so, you may hear or feel a click.

Hold the needle under the skin after the dose counter has returned to “0” and slowly count to 6 (Fig. C).
If you remove the needle from under your skin earlier, you can see the drug flow out of the needle. In this case, an incomplete dose of the drug will be administered.

Remove the needle from under the skin (fig. D). If blood appears at the injection site, lightly press a cotton swab over the injection site. Do not massage the injection site.
After the injection is complete, you can see a drop of solution at the end of the needle. This is normal and does not affect the dose you give.

(!) Always check the readings on the dose counter to know how much mg of the drug you have administered. Hold the trigger until the dose counter shows “0”.

How to find a blocked or damaged needle?

If after a long press on the trigger button, the dose counter does not show a “0”, this may mean a blockage or damage to the needle.
In this case, you have not received the drug, even if the dose counter has changed position from the original dose that you set.
What to do with a blocked needle?

Remove the needle as described in step 5 “After completing the injection” and repeat all steps starting from step 1 “Preparing the syringe pen with the needle for use”. Make sure to set the dose you want.

Never touch the dose counter while administering the drug. This can interrupt the injection.

5. After completion of the injection

With the outer needle cap on a flat surface, insert the tip of the needle into the cap without touching it or the needle (fig. A).

When the needle enters the cap, carefully slide the outer cap over the needle (fig. B).
Unscrew the needle and discard it carefully.

Put the cap on the pen after each injection to protect the solution it contains from light exposure (Fig. C).

Always discard the needle after each injection to ensure a comfortable injection and to avoid clogged needles. If the needle is blocked, you will not inject yourself.

Dispose of an empty pen with the needle disconnected according to the recommendations given by your doctor, nurse, pharmacist, or local regulations.

(!) Never try to put the inner cap back on the needle. You can inject yourself.

(!) Always remove the needle from the pen after each injection. This can prevent needle sticking, contamination, infection, solution leakage, and misdosing.

(!) Additional important information

Always keep the pen and needles out of the reach of everyone, and especially children, place.
Never share your pen and needles with others.
Caregivers must handle used needles with extreme care to prevent needle sticks and cross-infection.
Syringe pen care

Do not leave the pen in a car or any other place where it may be exposed to too high or too low temperatures.
Do not use Saxenda ® if it has been frozen. In this case, the expected effect of the drug will not be achieved.
Protect the pen from dust, dirt and all kinds of liquids.
Do not wash the pen, immerse it in liquid or lubricate it. If necessary, the pen can be cleaned with a damp cloth dampened in a mild detergent.
Do not drop or hit the pen on a hard surface. If you have dropped the syringe pen or are in doubt about its working capacity, attach a new needle and check the flow of the drug before giving the injection.
Refilling of the pen is not allowed. An empty pen must be discarded immediately.
Do not try to repair the pen or disassemble it yourself.
Side effect
The safety of Saxenda® was evaluated in 5 double-blind, placebo-controlled studies in 5813 obese or overweight patients with at least one overweight-related concomitant disease. In general, gastrointestinal disorders were the most frequently reported side effects during therapy with Saxenda ® (see “Description of selected adverse reactions”).

Table 3 provides a list of adverse reactions reported in long-term controlled phase 2 and 3 studies. Adverse reactions are categorized according to MedDRA organ systems and frequency. Determination of the frequency of adverse reactions: very often (≥1 / 10); often (≥1 / 100 to <1/10); infrequently (≥1 / 1000 to <1/100); rarely (> 1/10000 to <1/1000); very rare (<1/10000).

Table 3. Adverse reactions recorded during controlled studies of phases 2 and 3

Frequency Adverse reactions
From the immune system
Rarely Anaphylactic reactions
From the side of metabolism and nutrition
Often Hypoglycemia *
Infrequently Dehydration
Mental disorders
Often Insomnia**
From the nervous system
Often Dizziness **, dysgeusia **
On the part of the cardiovascular system
Infrequently Tachycardia
From the gastrointestinal tract
Often Nausea, vomiting, diarrhea, constipation
Often Dry mouth, dyspepsia, gastritis, gastroesophageal reflux, upper abdominal pain, flatulence, belching, bloating
Infrequently Pancreatitis ***, delayed gastric emptying ****
From the liver and biliary tract
Often Cholelithiasis ***
Infrequently Cholecystitis***
On the part of the skin and subcutaneous tissues
Infrequently Hives
From the urinary system
Rarely Acute renal failure, impaired renal function
General reactions and disorders at the injection site
Often Injection site reactions, asthenia **, fatigue **
Infrequently Malaise**
Laboratory research methods
Often Increased lipase activity, increased amylase activity
* Hypoglycemia (based on symptoms noted by patients and not confirmed by blood glucose measurements) noted in patients without T2DM who received Saxenda® in combination with diet and exercise. See “Descriptions of selected adverse reactions” for details.

** Mostly noted during the first 3 months of therapy.

*** See the “Special instructions” section.

**** In accordance with phases 2, 3a and 3b of a controlled clinical trial.

Description of selected adverse reactions

Hypoglycemia in patients without type 2 diabetes

In clinical studies involving patients with overweight or obesity without T2DM, who received therapy with Saxenda® in combination with diet and exercise, severe hypoglycemia (requiring assistance from a third party) was not observed. Symptoms of hypoglycemia were reported by 1.6% of patients receiving Saxenda® and 1.1 % of patients receiving placebo; however, these cases were not confirmed by blood glucose measurements. In most cases, there was mild hypoglycemia.

Hypoglycemia in patients with type 2 diabetes

In clinical studies involving patients with overweight or obesity and type 2 diabetes who received therapy with Saxenda® in combination with diet and exercise, cases of severe hypoglycemia (requiring the assistance of a third party) were observed in 0.7% of patients receiving Saxenda® . and only in patients simultaneously receiving therapy with sulfonylurea derivatives. 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 receiving Saxenda®, and 27.3% of patients receiving placebo. Among patients who did not receive a sulfonylurea drug at the same time, confirmed hypoglycemia was observed in 15.7% of patients receiving Saxenda® and in 7.6 % of patients receiving placebo.

Hypoglycemia in patients with type 2 diabetes mellitus receiving insulin

In clinical trials involving patients with overweight or obesity with type 2 diabetes, who received insulin therapy and Saxenda® in combination with diet and exercise and up to two oral hypoglycemic drugs, severe hypoglycemia (requiring assistance from a third person) was noted in 1.5 % of patients receiving therapy with Saxenda ® . In this study, confirmed hypoglycemia (defined as a plasma glucose level of ≤3.9 mmol / L accompanied by symptoms) was reported in 47.2% of patients treated with Saxenda®, and in 51.8% of patients receiving placebo. It was reported about confirmed hypoglycemic episodes among patients simultaneously receiving sulfonylurea derivatives, in 60.9% of patients receiving therapy with Saxenda® , and in 60.0 % of patients receiving placebo.

Adverse reactions from the gastrointestinal tract

Most of the reactions from the gastrointestinal tract 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 diminished 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® .

In patients with mild or moderate renal failure (CC ≥30 ml / min), more pronounced manifestations of adverse reactions from the gastrointestinal tract may be observed during therapy with Saxenda® .

Allergic reactions

In the post-registration period, the occurrence of several cases of anaphylactic reactions with symptoms such as arterial hypotension, palpitations, shortness of breath or peripheral edema was reported. Anaphylactic reactions can potentially be life threatening.

Injection site reactions

Reactions at the injection site have been reported in patients receiving Saxenda® . These reactions, as a rule, were mild, transient, and in most cases disappeared with continued therapy.

Tachycardia

In clinical studies, tachycardia was observed in 0.6% of patients receiving Saxenda® and in 0.1% of patients receiving placebo. Most of the events were mild to moderate. The phenomena were isolated and in most cases disappeared with continued therapy with Saxenda ® .

Children and adolescents

In a clinical study of obese adolescents aged 12 to 18 years, 125 patients received Saxenda® therapy for 56 weeks.

In general, the incidence, type and severity of adverse reactions in obese adolescents were comparable to those in adult patients. Vomiting in adolescents occurred twice as often as in adult patients.

No effect on growth or pubertal development was found.

Contraindications for use
hypersensitivity to liraglutide or any of the excipients of the drug;
history of medullary thyroid cancer, incl. in the family;
multiple endocrine neoplasia type 2;
severe depression, suicidal thoughts or behavior, incl. history.
The use is contraindicated in the following groups of patients and in the following conditions / diseases due to the lack of data on efficacy and safety:

severe renal failure (CC less than 30 ml / min);
severe liver failure;
children under 12 years of age;
adolescents aged 12 to 18 years with a body weight of ≤60 kg;
in patients aged ≥75 years;
pregnancy;
breastfeeding period;
chronic heart failure (CHF) IV functional class (in accordance with the NYHA classification);
the simultaneous use of other drugs for the correction of body weight;
use in combination with other GLP-1 receptor agonists;
secondary obesity due to endocrinological diseases or eating disorders, or against the background of the use of drugs that can lead to weight gain.
In patients with diabetes mellitus, Saxenda ® should not be used as an insulin substitute.

The experience of using Saxenda ® in patients with inflammatory bowel diseases and diabetic paresis of the stomach is limited. The use of liraglutide in these patients is not recommended because it is associated with transient gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea.

Carefully

Saxenda ® is recommended to be used with caution in patients with mild to moderate hepatic insufficiency, thyroid disease and a history of acute pancreatitis.

Application during pregnancy and lactation
Pregnancy

Data on the use of Saxenda ® in pregnant women are limited. Reproductive toxicity has been demonstrated in animal studies. The potential risk to humans is unknown.

The use of Saxenda ® during pregnancy is contraindicated. When planning or the onset of pregnancy, therapy with Saxenda ® must be discontinued.

Breastfeeding period

It is not known whether liraglutide passes into human breast milk. In animal studies, it has been demonstrated that the penetration of liraglutide and structurally related metabolites into breast milk is low. Preclinical studies have demonstrated therapy-related growth retardation in breastfed newborn rats. Due to the lack of experience in use, Saxenda ® is contraindicated during breastfeeding.

Fertility

With the exception of a slight decrease in the number of live embryos, the results of animal studies do not indicate an adverse effect on fertility.

special instructions
In patients with diabetes, Saxenda® should not be used as a substitute for insulin.

Diabetic ketoacidosis has been reported in patients receiving insulin therapy after rapid discontinuation or reduction in the insulin dose (see Dosage Regimen section).

Pancreatitis

The use of GLP-1 receptor agonists has been associated with the development of acute pancreatitis. Patients should be informed about the characteristic symptoms of acute pancreatitis.

In case of suspicion of the development of pancreatitis, the use of Saxenda ® should be discontinued; in case of confirmation of acute pancreatitis, therapy with Saxenda ® should not be resumed.

Cholelithiasis and cholecystitis

In clinical studies, a higher incidence of cholelithiasis and cholecystitis was noted in patients receiving Saxenda® compared with patients receiving placebo. This can be partially explained by the fact that a significant decrease in body weight when using the drug Saxenda ® may 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.

Diseases of the thyroid gland

In clinical trials involving patients with T2DM, adverse reactions from the thyroid gland have been noted, including an increase in serum calcitonin concentration, goiter, and thyroid neoplasms, especially in patients with pre-existing thyroid disease. In patients with thyroid diseases, Saxenda® should be used with caution.

In the post-marketing period, cases of medullary thyroid cancer were noted in patients receiving liraglutide. The available data are insufficient to establish or exclude a causal relationship for the occurrence of medullary thyroid cancer with the use of liraglutide in humans. Saxenda ® is contraindicated for use in patients with a history of medullary thyroid cancer, incl. in the family, 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 (neck lumps, dysphagia, shortness of breath, persistent hoarseness).

Current monitoring of the concentration of calcitonin in the blood serum or ultrasound of the thyroid gland are not essential for the early detection of medullary thyroid cancer in patients using Saxenda® . A significant increase in serum calcitonin concentration 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, further examination of the patient is necessary. Patients with thyroid nodules detected during a physical examination or with an ultrasound of the thyroid gland should also be further examined.

Heart rate

In clinical studies, an increase in heart rate was noted (see section “Pharmacological action” – Clinical efficacy and safety). 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, Saxenda® therapy should be discontinued .

Dehydration

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

Hypoglycemia in overweight or obese patients with type 2 diabetes

The risk of developing hypoglycemia may be higher in patients with T2DM receiving Saxenda® in combination with sulfonylurea derivatives. This risk can be reduced by lowering the dose of the 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 who received Saxenda® reported the appearance of suicidal thoughts, one of the patients attempted suicide. In patients (1941 people) who received placebo, this was not noted. Patients should be monitored for the onset or worsening of depression, suicidal thoughts or behavior, and / or any unexpected changes in mood or behavior. In patients with suicidal thoughts or behavior, 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 (BC)

In clinical trials, confirmed breast cancer was reported in 14 (0.6%) of 2379 women who received Saxenda® , compared with 3 (0.2%) of 1300 women who received placebo, including invasive cancer (11 cases in women who received Saxenda ® , and 3 cases in women who received placebo) and intraductal carcinoma in situ (3 cases in women who received Saxenda ® and 1 case in a woman who received placebo). Most cancers were estrogen- and progesterone-dependent. It is impossible 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 influence on already existing neoplasms of the mammary gland.

Papillary thyroid cancer

In clinical trials, confirmed papillary thyroid carcinoma was reported in 7 (0.2%) of 3291 patients treated with Saxenda® , compared with the absence of it in the placebo group (1843 patients). Of all the cases, 4 carcinomas were less than 1 cm in largest diameter and 4 were diagnosed based on histology after a medically indicated thyroidectomy.

Colon and rectal neoplasia

In clinical trials, confirmed benign neoplasms of the colon and rectum (predominantly colon adenomas) were reported in 17 (0.5%) of 3291 patients who received Saxenda® , compared with 4 (0.2%) of 1843 patients who received placebo. There were two confirmed cases of malignant carcinoma of the colon and rectum (0.1%) in patients receiving Saxenda® , and none in patients receiving placebo.

Cardiac conduction disorders

In clinical trials, 11 (0.3%) of 3384 patients who received Saxenda® reported the development of cardiac conduction disorders, such as grade I AV block, right bundle branch block or left bundle branch block. In patients (1941 people) who received placebo, the development of cardiac conduction disorders was not reported.

Preclinical safety data

Preclinical data based on safety pharmacology, repeated dose toxicity and genotoxicity studies have not identified any hazard to humans.

In two-year carcinogenicity studies in rats and mice, tumors of C-cells of the thyroid gland were detected, which did not lead to death. The results obtained from studies in rodents are due to the fact that rodents are particularly sensitive to the GLP-1 receptor-mediated non-genotoxic specific mechanism. No other neoplasms associated with the therapy were noted.

In animal studies, there was no direct adverse effect of the drug on fertility, but there was a slight increase in the incidence of early embryonic death with the use of the highest doses of the drug.

Influence on the ability to drive vehicles and mechanisms

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 T2DM, care should be taken when driving vehicles and mechanisms.

Overdose
Symptoms: according to clinical studies and post-registration use of liraglutide, cases of overdose have been reported when using the drug at a dose of 72 mg or more (24 times more than the recommended one for body weight correction). Patients reported severe nausea, severe vomiting, and severe hypoglycemia.

Treatment: in case of overdose, supportive therapy should be initiated according to the clinical signs and symptoms. The patient should be monitored for clinical signs of dehydration and blood glucose levels monitored.

Drug interactions
Assessment of drug interactions in vitro

Liraglutide has shown a very low ability for drug pharmacokinetic interactions due to metabolism in the cytochrome P450 (CYP) system, as well as binding to plasma proteins.

Assessment of drug interactions in vivo

A slight delay in gastric emptying when using liraglutide can affect the absorption of concomitantly used drugs for oral administration. Interaction studies have not shown any clinically significant slowdown in the absorption of these drugs, so no dose adjustment is required.

Interaction studies were carried out 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 3.0 mg (AUC 0-300 min of paracetamol). Several patients treated with liraglutide experienced at least one episode of severe diarrhea. Diarrhea can affect the absorption of oral medications that are used concomitantly with liraglutide.

Warfarin and other coumarin derivatives

Interaction studies have not been conducted. Clinically significant interactions with active substances with low solubility or a narrow therapeutic index, such as warfarin, cannot be excluded. At the beginning of treatment with Saxenda ® in patients receiving warfarin or other coumarin derivatives, it is recommended to monitor INR more often.

Paracetamol (acetaminophen)

Liraglutide did not alter the total exposure of paracetamol after administration of a single 1000 mg paracetamol dose. The C max of paracetamol was decreased by 31%, and the median T max was increased by 15 minutes. No dose adjustment is required with the concomitant use of paracetamol.

Atorvastatin

Liraglutide did not alter the total exposure of atorvastatin after a single dose of 40 mg atorvastatin. Therefore, dose adjustment of atorvastatin when used in combination with liraglutide is not required. The C max of atorvastatin was reduced by 38%, and the median T max was increased from 1 hour to 3 hours when using liraglutide.

Griseofulvin

Liraglutide did not change the total exposure of griseofulvin after a single dose of 500 mg griseofulvin. The C max of griseofulvin was increased by 37%, and the median T max did not change. No dose adjustment of griseofulvin and other compounds with low solubility and high penetrating power is required.

Digoxin

The use of a single dose of digoxin 1 mg in combination with liraglutide led to a decrease in the AUC of digoxin by 16%, a decrease in C max by 31%. The median T max of digoxin increased from 1 hour to 1.5 hours. Taking into account these results, no dose adjustment of digoxin is required.

Lisinopril

The use of a single dose of lisinopril 20 mg in combination with liraglutide led to a decrease in the AUC of lisinopril by 15%, a decrease in C max by 27%. When using liraglutide, the median T max of lisinopril increased from 6 hours to 8 hours. Taking into account these results, no dose adjustment of lisinopril is required.

Oral contraceptives

Liraglutide resulted in a 12% and 13% decrease in Cmax for ethinylestradiol and levonorgestrel, respectively, after a single dose of an oral hormonal contraceptive drug. The T max of both drugs increased by 1.5 hours against the background of the use of liraglutide. There was no clinically significant effect on the systemic exposure of ethinyl estradiol or levonorgestrel. Thus, no effect on the contraceptive effect is expected when combined with liraglutide.

Incompatibility

Medicinal substances added to Saxenda ® can cause destruction of liraglutide. Due to the lack of compatibility studies, this drug must not be mixed with other drugs.

Storage conditions of the drug Saxenda ®
The drug should be stored out of the reach of children at a temperature of 2 ° to 8 ° C (in the refrigerator), but not near the freezer. Do not freeze.

Store the used syringe pen with the drug at a temperature not exceeding 30 ° C or in a refrigerator (at a temperature of 2 ° C to 8 ° C). Do not freeze. Use within 1 month. Close the pen syringe with a cap to protect from light.

Shelf life of Saxenda ®
Expiration date – 30 months. Do not use after the expiration date indicated on the label of the syringe pen and packaging.
Terms of sale
The drug is available with a prescription.
Contacts for inquiries
NOVO NORDISK LLC