Victoza syringe pen 6mg/ml 3ml №2

Indications

Drug victosa^® indicated in adult patients with type 2 diabetes with diet and exercise to achieve glycemic control as:

- monotherapy;

- combination therapy with one or more oral hypoglycemic drugs (with Metformin, sulfonylurea derivatives or thiazolidinedione) in patients who have not achieved adequate glycemic control in previous therapy;

- combination therapy with basal insulin in patients who have not achieved adequate glycemic control during therapy with the drug Victoza ^® and metformin.

Dosage and administration

Drug victosa^® use 1 time / day at any time, regardless of the meal, it can be administered as a sc injection in the abdomen, thigh or shoulder. Place and time of injection may vary without dose adjustment. However, it is preferable to administer the drug at about the same time of day, at the time most convenient for the patient. Drug victosa^® can not be used for in / in and / m introduction.

Doses

The initial dose of the drug is 0.6 mg / day. After using the drug for at least one week, the dose should be increased to 1.2 mg. There is evidence that in some patients the effectiveness of treatment increases with an increase in the dose of the drug from 1.2 mg to 1.8 mg. In order to achieve the best glycemic control in the patient and taking into account the clinical effectiveness of the dose of the drug Victoza^® can be increased to 1.8 mg after applying it in a dose of 1.2 mg for at least one week. The use of the drug in a daily dose above 1.8 mg is not recommended.

Drug victosa^® It is recommended to use in addition to the existing therapy with metformin or combination therapy with metformin with thiazolidinedione. Therapy with metformin and thiazolidinedione can be continued in previous doses.

Drug victosa^® It is recommended to add to the ongoing therapy with sulfonylurea derivatives or to combination therapy with metformin with sulfonylurea derivatives. With the addition of the drug Victoza^® For sulfonylurea derivatives, consider reducing the dose of sulfonylureas in order to minimize the risk of unwanted hypoglycemia.

For dose adjustment drug Victoza^® does not require self-monitoring of blood glucose. However, at the beginning of therapy with the drug Victoza^® in combination with sulfonylurea derivatives, such self-monitoring of blood glucose may be required for dose adjustment of sulfonylurea derivatives.

No dose adjustment is required depending on age. There is limited experience with the drug in patients aged 75 and over.

No dose selection required patients with mild renal failure. There is limited experience with the drug in patients with moderate renal failure. Currently, the use of the drug Victoza^® at patients with severely impaired renal function, including in patients with end-stage renal diseaseis contraindicated.

Currently there is limited experience with the drug Victoza^® in patients with hepatic insufficiency, it is therefore contraindicated to use it in patients with mild, moderate, or severe hepatic impairment.

The lack of data on the use of the drug Victoza^® at patients under the age of 18 does not allow to recommend it for the treatment of patients in this group.

Drug victosa^® cannot be used if it looks different than a clear and colorless or almost colorless liquid.

Drug victosa^® Do not use if it has undergone freezing.

Drug victosa^® can be inserted using needles up to 8 mm long and up to 32G thick. The syringe pen is intended for use in combination with disposable injection needles NovoFayn^® or NovoTvist^®.

Injection needles are not included in the package.

The patient should be informed that the used needle should be thrown out after each injection, and also that it is impossible to store the syringe pen with the attached needle. Such a measure will prevent contamination, infection and leakage of the drug from the syringe pen and guarantees the accuracy of dosing.

Adverse effects

In clinical studies, the most frequently reported side effects of the gastrointestinal tract were: nausea and diarrhea (reported in> 10% of patients); vomiting, constipation, abdominal pain and dyspeptic phenomena (reported in ≥1%, but ≤10% of patients).

At the beginning of therapy with the drug Victoza^® These gastrointestinal side effects may occur more frequently, but as the treatment continues, reactions usually decrease over several days or weeks. Adverse reactions in the form of headache and upper respiratory tract infections were observed relatively frequently (1-10% of patients). In addition, it is possible the development of hypoglycemic conditions, especially when using the drug Victoza^® in combination with sulfonylurea derivatives (registered in> 10% of patients). Severe hypoglycemia mainly develop on the background of the combined use of the drug Victoza^® with sulfonylurea derivatives.

Serious side effects have been reported very rarely.

Table 1 provides information on the side effects identified in the course of long-term controlled clinical trials of phase III of the drug Victoza^® and with spontaneous (post-marketing) messages. Adverse reactions identified during long-term phase III clinical trials with a development frequency of> 5% are presented, provided that their incidence was higher in the group of patients who received the drug Victoza^®, compared with that in the group of patients receiving comparison drugs. Also included are adverse reactions with a development rate of ≥1%, provided that their frequency was 2 or more times higher than the frequency of adverse reactions in groups of patients who received treatment with comparative drugs.

The frequency of the remaining spontaneous (post-marketing) messages was calculated based on their occurrence during phase III clinical trials.

All the adverse reactions presented below, based on data obtained during clinical trials and in the post-marketing period, are divided into groups according to the frequency of development in accordance with MedDRA and organ systems. The incidence of adverse reactions is defined as: very often (≥1 / 10); often (≥1 / 100 to <1/10); infrequently (≥1 / 1000 to <1/100); rarely (≥1 / 10,000 to <1/1000).

Table 1. Adverse reactions identified during long-term placebo-controlled clinical trials of phase III and spontaneous (post-marketing) messages

n = 2501 patients receiving Victoza therapy^®

*cm. section "Special instructions"

Description of individual adverse reactions

Hypoglycemia

Most of the episodes of confirmed hypoglycemia reported during clinical trials were mild.

During clinical studies with the use of the drug Victoza^® in the form of monotherapy, there were no cases of severe hypoglycemia. Severe hypoglycemia can occur infrequently and is mainly observed when using the drug Victoza^® in combination with sulfonylurea derivatives (0.02 cases / patient per year). When using the drug Victoza^® in combination with other oral hypoglycemic drugs (not derived from sulfonylurea), hypoglycemia was observed very rarely (0.001 cases / patient per year).

During therapy with liraglutide at a dose of 1.8 mg in combination with insulin detemir and metformin, no cases of severe hypoglycemia were observed. The incidence of mild hypoglycemia was 0.228 cases / patient per year. In the groups of patients treated with liraglutide 1.8 mg and metformin, the incidence of mild hypoglycemia was 0.034 and 0.115 cases / patient per year, respectively.

Gastrointestinal adverse reactions

In most cases, nausea was mild or moderate, was transient and rarely led to the abolition of therapy.

20.7% of patients receiving the drug Victoza^® in combination with metformin, suffered at least one episode of nausea, and 12.6% - at least one episode of diarrhea. When using the drug Victoza^® in combination with sulfonylurea derivatives, at least one episode of nausea was observed in 9.1% of patients and at least in one case of diarrhea in 7.9%.

During long-term controlled clinical trials (26 weeks or more), the frequency of discontinuation of patients in the study due to the development of side effects was 7.8% in the group of patients who received the drug Victoza^®, and 3.4% in the group of patients receiving comparison drugs. The most frequent adverse reactions that led to the withdrawal of the drug Victoza^®, there was nausea (2.8% of patients) and vomiting (1.5%).

In patients over the age of 70 years, the incidence of adverse reactions from the gastrointestinal tract when using the drug Victoza^® may be higher.

When using the drug Victoza^® in patients with mild renal failure (CC ≤ 60-90 ml / min), the frequency of adverse reactions from the gastrointestinal tract may be higher.

Immunogenicity

Given the possibility of the immunogenic effect of protein and peptide drugs, the use of the drug Victoza^® in patients, can lead to the formation of antibodies to liraglutide.Antibody formation is noted on average in 8.6% of patients. The formation of antibodies does not reduce the effectiveness of the drug Victoza^®.

Reactions at the injection site

In long-term (26 weeks or more) controlled studies in approximately 2% patients receiving the drug Victoza^®, there were reactions at the injection site. These reactions were usually light in nature.

Pancreatitis

Several cases of acute pancreatitis (<0.2%) have been reported in long-term clinical studies. There are reports of cases of pancreatitis in the post-registration period. The incidence of pancreatitis does not differ from that in this population (patients with type 2 diabetes). Data allowing to confirm or refute the causal relationship of pancreatitis with the use of the drug Victoza^®are missing.

Adverse reactions from the thyroid gland

The overall frequency of adverse reactions from the thyroid gland in all intermediate and long-term clinical studies with liraglutide, placebo and comparison preparations is 33.5; 30.0 and 21.7 cases per 1000 patient-years of total exposure, respectively; and the incidence of serious adverse reactions is 5.4; 2.1 and 1.2 cases.

The most frequent side effects of the thyroid gland were thyroid neoplasms, increased serum calcitonin concentrations and goiter.The frequency of these phenomena per 1000 patient-years of exposure was 6.8; 10.9 and 5.4 cases, respectively, in patients treated with liraglutide, compared with 6.4; 10.7 and 2.1 cases in patients receiving placebo, and 2.4; 6.0 and 1.8 cases - in patients receiving comparison drugs.

Allergic reactions

In the post-registration period, allergic reactions such as urticaria, rash and itching were reported.

In the post-registration period when using the drug Victoza^® described several cases of Anaphylactic reactions, accompanied by symptoms such as arterial hypotension, palpitations, shortness of breath, edema.

Heart rate increase

Reported cases of increasing the heart rate when using the drug Victoza^®. In long-term clinical studies with the use of the drug Victoza^® the average increase in heart rate from baseline ranged from 2 to 3 beats / min. Long-term clinical effects have not been established.

Contraindications

- Hypersensitivity to the active substance or other components that make up the drug;

- pregnancy;

- breastfeeding period.

The drug should not be used in patients with diabetes mellitus type 1; in diabetic ketoacidosis.

Not recommended for use in patients:

- with severe impaired renal function;

- with impaired liver function;

- with heart failure III-IV functional class (in accordance with the classification of NYHA);

- with inflammatory bowel disease;

- with paresis of the stomach;

- in children under 18 years old.

Due to limited experience, it is recommended to use carefully in patients with heart failure I-II functional class (in accordance with the NYHA classification), impaired renal function of moderate severity, aged 75 years and older.

Use during pregnancy and lactation

Adequate data on the use of the drug Victoza^® pregnant women are absent. Animal studies have demonstrated reproductive toxicity of the drug. The potential risk to humans is unknown.

Drug victosa^® cannot be used during pregnancy, insulin treatment is recommended instead. If the patient is preparing for pregnancy, or the pregnancy has already begun, drug therapy Victoza^® must stop immediately.

It is not known whether liraglutide is excreted in breast milk of women. Animal studies have shown that the penetration of liraglutide and metabolites of a close structural bond into breast milk is low. Experience using the drug Victoza^® in lactating women is absent; use of the drug during breastfeeding is contraindicated.

Application for violations of the liver

Currently there is limited experience with the drug Victoza^® in patients with hepatic insufficiency, it is therefore contraindicated to use it in patients with mild, moderate, or severe hepatic impairment.

Application for violations of kidney function

No dose selection required patients with mild renal failure. There is limited experience with the drug in patients with moderate renal failure. Currently, the use of the drug Victoza^® at patients with severely impaired renal function, including in patients with end-stage renal diseaseis contraindicated.

Use in children

The lack of data on the use of the drug Victoza^® at patients under the age of 18 does not allow to recommend it for the treatment of patients in this group.

Use in elderly patients

Due to limited experience, it is recommended to use carefully in patients aged 75 and over.

special instructions

Use of the drug Victoza^® contraindicated in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Viktoza^® does not replace insulin.

The prescription of liraglutide in patients already receiving insulin has not been studied.

Experience using the drug Victoza^® in patients with heart failure I-II functional classes in accordance with the functional classification of chronic heart failure NYHA is limited. No experience with the drug Victoza^® in patients with heart failure of III-IV functional classes in accordance with the classification of chronic heart failure NYHA.

Experience using the drug Victoza^® in patients with inflammatory bowel disease and diabetic paresis of the stomach is limited, therefore, the use of the drug in these groups of patients is contraindicated. Use of the drug Victoza^® associated with the development of transient adverse reactions from the gastrointestinal tract, such as nausea, vomiting and diarrhea.

The use of other GLP-1 agonists has been associated with the risk of pancreatitis. Several cases of acute pancreatitis have been reported. Patients should be informed about the characteristic symptoms of acute pancreatitis: persistent severe abdominal pain. If pancreatitis is suspected by the drug Victoza^® and other potentially hazardous drugs should be discontinued immediately.

During clinical trials of the drug Victoza^® in individual patients (in particular, in patients who already have thyroid disease), side effects from the thyroid gland were reported, including an increase in serum calcitonin concentration, goiter and thyroid neoplasms.

During clinical trials, signs and symptoms of dehydration and renal failure were reported in patients taking the drug Victoza^®. Patients receiving the drug Victoza^® should be warned about the possible risk of dehydration due to side effects from the gastrointestinal tract and the need for their precautionary measures to avoid the development of hypovolemia.

Patients receiving the drug Victoza^® in combination with sulfonylureas, have an increased risk of hypoglycemia. The risk of hypoglycemia can be reduced by reducing the dose of sulfonylurea derivatives.

Influence on ability to drive motor transport and control mechanisms

Research on the effect of the drug Victoza^® the ability to drive vehicles and work with mechanisms was not carried out. It is unlikely that liraglutide can affect the ability to drive a vehicle or work with machinery.

Patients should be warned that they should take precautions to avoid developing hypoglycemia in them while driving and working with machinery, especially when using the drug Victoza^® in combination with sulfonylurea derivatives.

Overdose

Symptoms: during clinical trials and post-marketing period, cases of the use of the drug Victoza were reported^® in doses up to 40 times the average recommended dose (72 mg), which was accompanied by the development of severe nausea and vomiting. No cases of severe hypoglycemia were noted. All patients recovered completely without complications.

Treatment: in case of drug overdose Victoza^® appropriate symptomatic therapy is recommended.

Drug interaction

Evaluation of the interaction of drugs in vitro

Lyraglutide showed a very low capacity for drug pharmacokinetic interaction,due to metabolism in the cytochrome P450 system, as well as binding to plasma proteins .

Evaluation of the interaction of drugs in vivo

A slight delay in gastric emptying with liraglutide may affect the absorption of concomitant oral medications. Studies of drug interactions have not shown any clinically significant delay in the absorption of these drugs. In several patients treated with Victoza^®, there was at least one episode of acute diarrhea. Diarrhea can affect the absorption of oral medications, which are used simultaneously with the drug Victoza^®.

Paracetamol

A single application of Paracetamol in a dose of 1000 mg against the background of the use of liraglutide does not cause a change in systemic exposure. C_max paracetamol in plasma decreased by 31%, and the average time to reach C_max in blood plasma increased by 15 min. With the simultaneous use of liraglutide and paracetamol dose adjustment is not required.

Atorvastatin

A single application of Atorvastatin in a dose of 40 mg against the background of the use of liraglutide does not cause a change in systemic exposure. Thus, while taking the drug Victoza^® Atorvastatin dose adjustment is not required. C_max atorvastatin in plasma decreased by 38%, and the average time to reach C_max in plasma with liraglutide intake increased from 1 to 3 h.

Griseofulvin

A single application of Griseofulvin in a dose of 500 mg against the background of the use of liraglutide does not cause a change in systemic exposure. C_max Griseofulvin increased by 37%, while the average time to reach C_max in plasma has not changed. Dose adjustment of griseofulvina and other drugs with low solubility and high permeability is not required.

Digoxin

With simultaneous single administration of Digoxin at a dose of 1 mg and liraglutide, a decrease in AUC of digoxin was noted by 16%; C_max digoxin decreased by 31%. Average time to reach C_max digoxin in plasma increased from 1 to 1.5 h. On the basis of the results obtained, the dose adjustment of digoxin during the administration of liraglutide is not required.

Lisinopril

A single application of lisinopril in a dose of 20 mg against the background of the use of liraglutide resulted in a 15% decrease in the AUC of lisinopril; C_max lisinopril decreased by 27%. Average time to reach C_max lisinopril in plasma with liraglutide intake increased from 6 to 8 h.

Oral contraceptives

C_max ethinyl estradiol and levonorgestrel after their single use during therapy with liraglutide decreased by 12% and 13%, respectively. The use of both drugs together with liraglutid was accompanied by an increase in the time to achieve C_max these medicines for 1.5 hours. There is no clinically significant effect on the systemic exposure of ethinyl estradiol and levonorgestrel in the body to liraglutide.Thus, the expected contraceptive effect of both drugs does not change during therapy with liraglutide.

Warfarin and other coumarin derivatives

Interaction studies have not been conducted. At the beginning of treatment with the drug Victoza^® in patients receiving Warfarin or other coumarin derivatives, it is recommended to monitor the INR more frequently.

Insulin

No pharmacokinetic or pharmacodynamic interaction of liraglutide with insulin detemir was detected with a single use of insulin detemir at a dose of 0.5 U / kg with liraglutide at a dose of 1.8 mg in patients with type 2 diabetes.

Pharmaceutical incompatibility

Substances added to the drug Victoza^®may cause degradation of liraglutide. Drug victosa^® must not be mixed with other drugs, incl. with infusion solutions.

Terms and conditions of storage

The drug should be stored out of the reach of children, at a temperature of 2 ° to 8 ° C (in the refrigerator); do not freeze. Do not use after the expiration date indicated on the label the syringe pen and packaging.

A pen syringe in use should be used within 1 month. Store at a temperature not higher than 30 ° С or from 2 ° to 8 ° С (in the refrigerator); do not freeze. Cover the pen with a cap to protect it from light.