Instruction for use: Tudzheo SoloStar

Active substance Insulin glargine

ATX codeA10AE04 Insulin glargine

Pharmacological group of substance Calcitonin

Hypoglycemic agent. Long-acting insulin [Insulins]

Nosological classification (ICD-10)

E10 Insulin-dependent diabetes mellitus

Decompensation of carbohydrate metabolism, Diabetes mellitus, Diabetes insulin sugar, Diabetes mellitus type 1, Diabetic ketoacidosis, Insulin-dependent diabetes, Insulin-dependent diabetes mellitus, Coma hyperosmolar non-ketoacidotic, Labile form of diabetes mellitus, Violation of carbohydrate metabolism, Type 1 diabetes mellitus, Type I diabetes mellitus, Insulin-dependent diabetes mellitus, Type 1 diabetes mellitus

E11 Non-insulin-dependent diabetes mellitus

Acetonuric diabetes, Decompensation of carbohydrate metabolism, Diabetes insulin-independent sugar, Diabetes sugar type 2, Type 2 Diabetes, Non-insulin-dependent diabetes, Non-insulin dependent diabetes mellitus, Non-insulin-dependent diabetes mellitus, Insulin resistance, Insulin resistant diabetes mellitus, Coma lactobacillus diabetic, Violation of carbohydrate metabolism, Type 2 diabetes mellitus, Diabetes mellitus type II, Diabetes mellitus in adulthood, Diabetes mellitus in old age, Diabetes insulin-independent, Diabetes mellitus type 2, Sugar insulin-independent diabetes type II

Composition

Solution for subcutaneous administration 1 ml

active substance:

Insulin glargine 300 units (10.91 mg)

Auxiliary substances: metacresol (m-cresol) - 2.7 mg; Zinc chloride 0.19 mg (corresponding to 0.09 mg of zinc); Glycerol (85%) - 20 mg; Sodium hydroxide - up to pH 4; Hydrochloric acid - up to pH 4; Water for injection - up to 1 ml

Description of dosage form

A clear, colorless or almost colorless solution.

pharmachologic effect

Pharmacological action - hypoglycemic.

Pharmacodynamics

The most important action of insulin, incl. And insulin glargine, is the regulation of glucose metabolism. Insulin and its analogues reduce the concentration of glucose in the blood, stimulating the absorption of glucose by peripheral tissues (especially skeletal muscle and fat tissue) and inhibiting the formation of glucose in the liver. Insulin inhibits lipolysis in adipocytes (fat cells) and inhibits proteolysis, while increasing protein synthesis.

Pharmacodynamic characteristics

Insulin glargine is an analog of human insulin, obtained by recombinant DNA of bacteria of the species Escherichia coli (strains K12) used as a producer strain. It has low solubility in a neutral medium. At pH 4 (in an acidic medium), the insulin glargine is completely soluble. After introduction into the subcutaneous fat cellulose the acid reaction of the solution is neutralized, which leads to the formation of micro-precipitates, from which small amounts of insulin glargine are constantly released.

The onset of action of the insulin glargine 100 U / ml insulin was slower than that of human insulin isophane, the curve of its action was smooth and devoid of peaks, and the duration of its action was prolonged (data from euglycemic clamp studies conducted in healthy volunteers and patients With type 1 diabetes mellitus).

The hypoglycemic effect of Tudzheo SoloStar® after its administration was inferior to that of insulin glargine 100 U / ml insulin, which was more constant in magnitude and more prolonged (data from a 36-hour cross-eaglycemic clamp test conducted in 18 patients With type 1 diabetes mellitus). The effect of Tudzheo SoloStar® continued for more than 24 hours (up to 36 hours) with its administration to the clinically significant doses

- the vertical axis indicates the rate of glucose infusion, mg / kg · min;

- on the horizontal scale - time after injection, h.

The solid line on the chart indicates Treatment with TUDZHEOO 0.4 U / kg; The dotted line 0 treatment with insulin glargine 100 U / ml.

The prolonged hypoglycemic effect of Tudzheo SoloStar®, which lasts for more than 24 hours, allows, if necessary, to change the time of administration of the drug within 3 hours before or 3 hours after the usual injection time for the patient (see "Method of administration and dose").

Differences in the curves of the hypoglycemic effect of Tudzheo SoloStar® and insulin glargin 100 U / ml are associated with a change in the release of insulin glargine from the precipitate.

For the same amount of insulin glargine, the injected volume of Tudzhelo SoloStar® is one third of that given insulin glargine 100 U / ml. This leads to a decrease in the surface area of the precipitate, which provides a more gradual release of insulin glargine from the precipitate of Tudzheo SoloStar® as compared to 100g / ml of glargine insulin.

With iv introduction of identical doses of insulin glargine and human insulin, their hypoglycemic effect was the same.

Connection with insulin receptors. Insulin glargine is metabolized to two active metabolites M1 and M2 (see "Pharmacokinetics"). In vitro studies have shown that the affinity of insulin glargine and its metabolites M1 and M2 to human insulin receptors is similar to that of human insulin.

Communication with the IGF-1 receptors. The affinity of insulin glargine to the IGF-1 receptor is approximately 5-8 times higher than in human insulin (but approximately 70-80 times lower than in IGF-1), while at the same time compared to human insulin, the metabolites of insulin glargine M1 and M2 have a somewhat lower affinity for the IGF-1 receptor. The total therapeutic concentration of insulin (the concentration of insulin glargine and its metabolites), determined in patients with type 1 diabetes mellitus, was markedly lower than that required for half-maximal binding to IGF-1 receptors and subsequent activation of the mitogen-proliferative pathway through IGF-1 receptors . The physiological concentrations of endogenous IGF-1 can activate the mitogen-proliferative pathway, however the therapeutic insulin concentrations determined by insulin therapy, including treatment with Tudzheo SoloStar®, are significantly lower than the pharmacological concentrations required to activate the mitogenic-proliferative pathway.

The results obtained in all clinical studies of Tudzheo SoloStar®, conducted with the participation of a total of 546 patients with type 1 diabetes mellitus and 2474 patients with type 2 diabetes mellitus, showed that the decrease in glycosylated hemoglobin (HbAlc) compared to their original Values by the end of the study was no less than that for insulin glargine treatment 100 U / ml.

The percentage of patients achieving the target HbA1c (below 7%) was comparable in both treatment groups.

Reducing plasma glucose concentrations by the end of the study with Tudzheo SoloStar® and insulin glargine 100 U / ml was the same, but with the Tudzheo SoloStar® treatment, the decline was more gradual during the dose selection period.

Glycemic control, including an improvement in HbAlc, when administered with Tudzheo SoloStar® in the morning or evening was comparable, and a change in administration time between 3 hours before or 3 hours after the patient's usual administration time did not affect its effectiveness.

Patients treated with Tudzheo SoloStar® showed a change in body weight at the end of the 6-month therapy period, on average less than 1 kg.

The improvement in HbA1c was independent of sex, ethnicity, age, duration of diabetes (<10 and ≥10 years), HbAlc outcome (<8 or ≥8%), or BMI in outcome.

In patients with type 2 diabetes mellitus, the results of clinical trials demonstrated a lower incidence of severe and / or confirmed hypoglycemia, as well as documented hypoglycemia with clinical symptoms, when treated with Tudzheo SoloStar®, compared with insulin glargine 100 U / ml.

The advantage of TUDZHEO SoloStar® before insulin glargine of 100 U / ml in reducing the risk of developing severe and / or confirmed nocturnal hypoglycemia was shown in patients who had previously received oral hypoglycemic drugs (23% risk reduction) or insulin at meal time (21% risk reduction ) During the period from the 9th week to the end of the study, compared with the treatment with insulin glargine 100 U / ml.

In the group of patients treated with Tudzheo SoloStar®, compared with patients treated with insulin glargine 100 U / ml, a reduction in the risk of hypoglycemia was observed in patients who had previously received insulin therapy and in patients who had not previously received insulin; The risk reduction was greater during the first 8 weeks of treatment (initial treatment period) and did not depend on age, sex, race, BMI and duration of diabetes (<10 and ≥10 years).

In patients with type 1 diabetes mellitus, the incidence of hypoglycemia with Tudzheo SoloStar® was similar to that in patients treated with insulin glargine 100 U / ml. However, the incidence of nocturnal hypoglycemia (for all hypoglycaemia categories) during the initial treatment period was lower in patients treated with Tudzheo SoloStar® than in patients treated with insulin glargine 100 U / ml.

In clinical trials, a single administration of Tudzheo SoloStar® in the evening, with a fixed schedule of administration (at the same time) or a flexible schedule of administration (at least 2 times a week, the drug was administered 3 hours before or 3 hours after the usual Of the administration time, whereby the intervals between administrations were shortened to 18 hours or extended to 30 hours) had the same effect on the HbA1c index, fasting plasma glucose (GPN) concentration and the average pre-injection concentration of glucose Oz in blood plasma for self-determination. In addition, with the use of Tudzheo SoloStar® with a fixed or flexible time schedule, there was no difference in the incidence of hypoglycaemia at any time of the day or night hypoglycemia. The results of the studies did not indicate any differences in the formation of antibodies to insulin in the efficacy, safety or dose of basal insulin between patients treated with Tudzheo SoloStar® and insulin glargine 100 U / ml (see "Side effects"). . The ORIGIN study was an international, multicenter, randomized study conducted in 12537 patients with impaired fasting glucose (NGH), impaired glucose tolerance (NTG) or early stage 2 diabetes mellitus and confirmed cardiovascular disease. Participants in the study were randomly assigned to groups receiving insulin glargine ≤100 U / ml (n = 6264), which was titrated to a GPN concentration of <5.3 mmol, or standard treatment (n = 6273). The mean value of the follow-up period was approximately 6.2 years.

The median of the initial HbA1c values was 6.4%. The average value of HbA1c during treatment was in the range of 5.9-6.4% in the group of insulin glargine and 6.2-6.6% in the standard treatment group throughout the observation period.

The ORIGIN study showed that treatment with insulin glargine 100 U / ml compared with standard hypoglycemic therapy did not change the risk of cardiovascular events (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke), the risk of revascularization procedure (coronary, carotid or Peripheral arteries) or hospitalization for the development of heart failure, the risk of developing microvascular complications (combined index of microvascular complications: conduction of a Corneal photocoagulation or vitrectomy, loss of vision due to diabetic retinopathy, progression of albuminuria or a doubling of the creatinine concentration in the blood, or the emergence of the need for dialysis therapy).

In a study evaluating the effect of insulin glargin 100 U / ml on the development of diabetic retinopathy, there was no significant difference in the progression of diabetic retinopathy in insulin glargine 100 U / ml compared with insulin isophane in five-year follow-up of patients with type 2 diabetes mellitus.

Special patient groups

Sexual and racial affiliation. There were no differences in the efficacy and safety of Tudzheo SoloStar® and insulin glargin 100 U / ml, depending on the sex and race of patients.

Elderly age. In controlled clinical trials, 716 patients (23% of the population for safety assessment) with type 1 and type 2 diabetes were aged ≥65 years and 97 patients (3%) were ≥75 years of age. In general, there was no difference in efficacy and safety between these patients and younger patients. In elderly patients with diabetes mellitus, to avoid hypoglycemic reactions, the initial and maintenance dose should be lower, and the dose increase is slower. Elderly patients may have difficulty in recognizing hypoglycemia. It is recommended that the blood glucose concentration be carefully monitored, and the insulin dose should be adjusted individually (see "Dosage and Administration" and "Pharmacokinetics").

Renal insufficiency. In controlled clinical trials, subgroup analysis based on the functional state of the kidneys (defined in the outcome by GFR <60 or ≥60 ml / min / 1.73 m2 body surface area) showed no difference in safety and efficacy between Tudzheo SoloStar® and insulin glargine 100 units / ml. It is recommended that the blood glucose concentration be carefully monitored, and the insulin dose should be adjusted individually (see "Dosage and Administration" and "Pharmacokinetics").

Patients with obesity. In clinical studies, subgroup analysis based on BMI (up to 63 kg / m2) showed no difference in efficacy and safety between Tudzheo SoloStar® and insulin glargine 100 U / ml.

Children. Data on the use of Tudzheo SoloStar® in children is not available.

Pharmacokinetics

Absorption and distribution. After the injection of Tudzheo SoloStar® to healthy volunteers and patients with diabetes mellitus, serum insulin concentration indicates a much slower and more prolonged absorption, which results in a more flat AUC curve for up to 36 hours compared with insulin glargine 100 U / Ml. The AUC curve of Tudzheo SoloStar® was consistent with the curve of its pharmacodynamic activity. Css within the therapeutic range of concentrations was achieved after 3-4 days of daily use of Tudzheo SoloStar®.

After injection of Tudzheo SoloStar®, the variability in the same patient, defined as the coefficient of variation in the systemic exposure of insulin for 24 hours in the Css-reaching state, was low (17.4%).

Metabolism. In humans, after the administration of Tudzheo SoloStar®, insulin glargine is rapidly metabolized from the carboxyl terminus (C-terminus) of the β chain to form two active metabolites of M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B -Thr-insulin). The M1 metabolite predominantly circulates in the blood plasma. Systemic exposure of M1 metabolite increases with increasing dose of Tudzheo SoloStar®. Comparison of pharmacokinetics and pharmacodynamics data showed that the effect of the drug is mainly due to the systemic exposure of the metabolite M1. The overwhelming majority of patients failed to detect insulin glargine and M2 metabolite in the systemic circulation. In cases when it was possible to detect in the blood insulin glargine and metabolite M2, their concentrations did not depend on the administered dose and the dosage form of insulin glargine.

Excretion. T1 / 2 metabolite M1, the quantitatively prevalent metabolite of the drug Tudzio SoloStar®, after sc injection of the drug is 18-19 hours, regardless of dose.

Special patient groups

Sexual and racial affiliation. Information on the effect of race and sex on the pharmacokinetics of insulin glargine is absent (see "Pharmacodynamics").

Elderly age. The influence of age on the pharmacokinetics of Tudzheo SoloStar® has not been studied to date. In elderly patients with diabetes, in order to avoid hypoglycemic reactions, the initial dose and maintenance dose should be lower, and the dose should be increased more slowly (see "Pharmacodynamics" and "Method of administration and dose").

Children. In children, the pharmacokinetics of Tudzheo SoloStar® have not been studied at this time.

Renal and hepatic insufficiency. The effect of renal and hepatic insufficiency on the pharmacokinetics of Tudzheo SoloStar® has not been studied to date. However, in some studies conducted with human insulin, an increase in insulin concentrations in patients with renal and hepatic insufficiency was shown. It is recommended that blood glucose concentration in the blood be carefully monitored and individual insulin dose adjustment (see "Dosage and Administration" and "Pharmacodynamics").

Indications

Diabetes in adults requiring treatment with insulin.

Contraindications

Hypersensitivity to insulin glargine or any of the excipients of the drug;

Age to 18 years (due to the lack of clinical data confirming the efficacy and safety of the drug in children and adolescents).

With caution: pregnant women (the possibility of changing the need for insulin during pregnancy and after childbirth), elderly patients (see "Pharmacokinetics", "Pharmacodynamics", "Method of administration and dose" and "Special instructions"); Patients with uncompensated endocrine disorders (such as hypothyroidism, adenohypophysis failure and adrenal cortex); Diseases accompanied by vomiting or diarrhea; Severe stenosis of the coronary arteries or vessels of the brain; Proliferative retinopathy (especially if patients did not undergo photocoagulation); Kidney failure; Severe hepatic insufficiency (see "Special instructions").

pregnancy and lactation

Patients with diabetes should inform the attending physician of an existing or planned pregnancy.

There were no randomized controlled clinical trials on the use of Tudzheo SoloStar® in pregnant women.

A large number of observations (more than 1000 outcomes of pregnancies with retrospective and prospective observation) with the use of insulin glargin 100 U / ml aftermarketing showed no specific effects on the course and outcome of pregnancy, fetal status or neonatal health.

In addition, in order to assess the safety of the use of insulin glargine and insulin isophane in pregnant women with pre-existing or gestational diabetes mellitus, a meta-analysis of eight observational clinical trials was carried out, including women who had insulin glargine 100 U / ml during pregnancy (n = 331) and insulin isophane (n = 371). This meta-analysis did not reveal significant differences regarding the safety of maternal or newborn health, with the use of insulin glargine and insulin isophane during pregnancy.

In animal studies, no direct or indirect data were obtained on the embryotoxic or fetotoxic effect of insulin glargin 100 U / ml when administered at doses 6-40 times the recommended doses in humans.

For patients with pre-existing or gestational diabetes mellitus, it is important during the entire pregnancy to maintain adequate regulation of metabolic processes to prevent the emergence of unwanted outcomes associated with hyperglycemia.

If necessary, the use of Tudzheo SoloStar® in pregnancy may be considered.

The need for insulin can decrease in the first trimester of pregnancy and, in general, increase during the II and III trimesters. Immediately after delivery, the need for insulin decreases rapidly (the risk of developing hypoglycemia increases). In these conditions, careful monitoring of the concentration of glucose in the blood is essential.

Patients during breastfeeding may need to adjust the dosage regimen of insulin and diet.

Side effects

The following undesirable reactions (HP) were observed during clinical trials with Tudzheo SoloStar® and during the clinical use of 100 mg / ml of glargine insulin. These HPs are represented by organ systems (according to the MedDRA classification in accordance with the recommended WHO guidelines for the following incidence rates: very often (≥10%), often (≥1; <10%), infrequently (≥0,1; <1 %), Rarely (≥0.01, <0.1%), very rarely (<0.01%), the frequency is unknown (it is not possible to determine the frequency of occurrence of HP according to available data).

From the side of metabolism and nutrition: hypoglycemia. Hypoglycemia, the most common undesirable reaction in insulin therapy, can occur if the dose of insulin is too high compared to the need for it. As with the use of other insulins, episodes of severe hypoglycemia, especially recurrent, can lead to neurologic disorders.

Episodes of prolonged and severe hypoglycemia can endanger the lives of patients.

In many patients, signs and symptoms of neuroglycopenia (fatigue, inadequate fatigue or weakness, decreased ability to concentrate, drowsiness, visual disturbances, headache, nausea, confusion or loss of it, convulsive syndrome) precede signs of adrenergic counterregulation (sympathetic adrenal activation System in response to hypoglycemia) - hunger, irritability, nervous excitement or tremor, anxiety, pale skin, cold sweat, tachycardia, vomiting Heart palpitations. Usually, the faster the hypoglycemia develops and the more severe it is, the stronger the symptoms of adrenergic counterregulation.

From the side of the eye: a significant improvement in glycemic control may cause temporary visual impairment due to temporary disruption of the turgor and the refractive index of the lens of the eye.

Long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy. However, as with any scheme of prescribing insulin, the intensification of insulin therapy with a sharp improvement in glycemic control may be associated with a temporary increase in the course of diabetic retinopathy.

In patients with proliferative retinopathy, especially those who do not receive photocoagulation treatment, episodes of severe hypoglycemia can lead to transient loss of vision.

From the skin and subcutaneous tissues: as with any other insulin preparations, lipodystrophy can be developed at the injection site that can slow the local absorption of insulin. With the use of insulin regimens including insulin glargine, lipodystrophy was observed in 1-2% of patients, and lipoatrophy was infrequent. The constant change of injection sites within the body regions recommended for insulin administration may help to reduce the severity of this reaction or prevent its development.

From the musculoskeletal and connective tissue: very rarely - myalgia.

General disorders and disorders at the site of administration: local allergic reactions at the site of administration. As with any insulin therapy, such reactions include redness of the skin, pain, itching, hives, rashes, swelling and inflammation. In clinical studies conducted in adult patients, the frequency of all reactions at the site of administration in patients treated with Tudzheo SoloStar® (2.5%) was similar to that in patients treated with insulin glargine 100 U / ml (2.8% ). Most minor reactions at the site of insulin administration usually take place within a few days or a few weeks.

From the immune system: systemic allergic reactions. Allergic reactions of an immediate type to insulin are rare. Such reactions to insulin (including insulin glargine) or excipients may, for example, be accompanied by generalized skin reactions, angioedema (Quincke's edema), bronchospasm, lowering of blood pressure and shock, and a threat to the life of the patient.

Other reactions: the use of insulin can cause the formation of antibodies to it. In clinical studies comparing the Tudzheo SoloStar® and insulin glargin 100 U / ml, the formation of antibodies to insulin in both treatment groups was observed with equal frequency. As with the use of other insulins, in rare cases, the presence of such antibodies to insulin may require a change in the dose of insulin in order to eliminate the tendency to develop hypoglycemia or hyperglycemia.

In rare cases, insulin can cause sodium retention and the appearance of edema, especially when improving previously inadequate metabolic control in the intensification of insulin therapy.

Children. The safety profile for children and adolescents under the age of 18 is not currently established.

Interaction

A number of drugs affect the metabolism of glucose, so that when they are used simultaneously with insulin, you may need to adjust the dose of insulin and especially careful observation.

Drugs (drugs) that can increase the hypoglycemic effect of insulin and the tendency to develop hypoglycemia. Oral hypoglycemic agents, ACE inhibitors, salicylates, disopyramide; Fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, sulfonamide antibiotics. Simultaneous reception of these drugs with insulin glargine may require correction of the dose of insulin.

Drugs that can weaken the hypoglycemic action of insulin. GCS, danazol, diazoxide, diuretics, sympathomimetics (such as epinephrine, salbutamol, terbutaline); Glucagon, isoniazid, phenothiazine derivatives, somatotropic hormone, thyroid hormones, estrogens and gestagens (eg in hormonal contraceptives), protease inhibitors and atypical antipsychotics (eg olanzapine and clozapine). Simultaneous reception of these drugs with insulin glargine may require correction of the dose of insulin.

Beta-adrenoblockers, clonidine, lithium salts and ethanol - is possible as an enhancement, and weakening of hypoglycemic action of insulin.

Pentamidine, when combined with insulin, can cause hypoglycemia, which is sometimes replaced by hyperglycemia.

Sympatholytic drugs - under the influence of sympatholytic agents, such as beta-blockers, clonidine, guanethidine and reserpine, signs of adrenergic counterregulation (activation of the sympathetic nervous system in response to the development of hypoglycemia) may be reduced or absent.

Interaction with pioglitazone. When pioglitazone was used in combination with insulin, cases of heart failure were reported, especially in patients at risk of developing heart failure (see "Special instructions"). With the appearance or weighting of cardiac symptoms, the use of pioglitazone should be discontinued.

Dosing and Administration

General recommendations

The units of Tudzheo SoloStar® (insulin glargine 300 U / ml) are only for Tudzheo SoloStar® and are not equivalent to other units expressing the strength of the action of other insulin analogues. Tudzheo SoloStar® should be given once a day at any time of the day, preferably at the same time. Tudzheo SoloStar®, once given once a day, allows for a flexible schedule for injections: if necessary, patients can be injected for 3 hours before or 3 hours after the usual time for them.

Target values of blood glucose concentration, dose and time of intake / administration of hypoglycemic drugs should be determined and adjusted individually.

Correction of the dose may also be required, for example, with a change in the patient's body weight, lifestyle, changes in the time of insulin administration, or in other conditions that may increase the predisposition to hypo- or hyperglycaemia (see "Special instructions"). Any changes in the dose of insulin should be conducted with caution and only under medical supervision. Tudzheo SoloStar® is not an insulin of choice for the treatment of diabetic ketoacidosis. In this case, preference should be given to / in the introduction of short-acting insulin.

In all patients with diabetes it is recommended to monitor the concentration of glucose in the blood.

Initiation of Tudzheo SoloStar®

Patients with type 1 diabetes mellitus. Tudzheo SoloStar® should be applied once a day in combination with insulin administered during meals and requires an individual dose adjustment.

Patients with type 2 diabetes mellitus. The recommended initial dose is 0.2 U / kg 1 time per day with subsequent individual dose adjustment.

Transition from the introduction of insulin glargin 100 U / ml on the drug Tudzheo SoloStar ® and, conversely, from the drug Tudzheo SoloStar ® on insulin glargine 100 U / ml

Insulin glargine 100 U / ml and the drug Tudzheo SoloStar® are nonbioequivalent and are not directly interchangeable.

- The transition from insulin glargin 100 U / ml to the Tudzheo SoloStar® preparation may be based on a unit per unit, but a higher dose of Tudzheo SoloStar® may be required to achieve the target range of plasma glucose concentrations.

- When switching from Tudzheo SoloStar® to insulin glargine 100 U / ml to reduce the risk of hypoglycemia, the dose should be reduced (approximately 20%), followed by dose adjustment if necessary.

It is recommended that careful metabolic monitoring be performed during and for the first few weeks after switching from one of these drugs to another.

Transition from other basal insulins to Tudzheo SoloStar®

When switching from a treatment regimen with insulin of intermediate and long duration of action to a treatment regimen with Tudzheo SoloStar®, a change in the dose of basal insulin and correction of concomitant hypoglycemic therapy (changes in the doses and timing of short-acting insulin or fast-acting insulin analogues, or doses of non-insulin hypoglycemic Preparations).

- Transition from a single day during the day of basal insulin administration for a single day during the day, the administration of Tudzhelo SoloStar® can be carried out at a unit per unit of the previously administered dose of basal insulin.

- When switching from twice daily basal insulin administration to a single injection of Tudzio SoloStar®, the recommended initial dose of Tudzheo SoloStar® is 80% of the total daily dose of basal insulin, the treatment of which ceases. Patients with high doses of insulin, due to their antibodies to human insulin, may have an improved response to Tudzheo SoloStar®.

During the transition to Tudzheo SoloStar® and within a few weeks after it, careful metabolic monitoring is recommended.

With an improvement in metabolic control and the resulting increase in insulin sensitivity, additional dosage adjustment may be required. Correction of the dosing regimen may also be required, for example, with a change in the body weight or lifestyle of the patient, with a change in the time of administration of the insulin dose, or with the emergence of other conditions that increase the predisposition to the development of hypo- and hyperglycemia.

Transition from the introduction of Tudzheo SoloStar® to other basal insulins

During the transition from the introduction of Tudzheo SoloStar® to the use of other basal insulins and for several weeks after it, medical supervision and careful metabolic monitoring are recommended.

It is recommended that you consult the instructions for the use of the medication to which the patient is being referred.

Mixing and dilution

Tudzheo SoloStar® should not be mixed with any other insulin. Mixing leads to a change in the profile of the Tudzheo SoloStar® action in time and causes precipitation. Tudzheo SoloStar® can not be diluted. Breeding can lead to a change in the profile of the Tudzheo SoloStar® in time.

Special patient groups

Children. The safety and effectiveness of Tudzheo SoloStar® in children and adolescents under 18 years of age have not been established (see "Pharmacokinetics").

Elderly age. Tudzheo SoloStar® can be used in elderly patients. It is recommended to carefully monitor the concentration of glucose in the blood, and the dose of insulin should be selected individually. In elderly patients, progressive impairment of kidney function can lead to a permanent decrease in the need for insulin (see "Special instructions", "Pharmacodynamics" and "Pharmacokinetics").

Renal insufficiency. Tudzheo SoloStar® can be used in patients with renal insufficiency. It is recommended to carefully monitor the concentration of glucose in the blood, and the dose of insulin should be selected individually. In patients with renal insufficiency, the need for insulin may decrease as a result of a slowdown in the metabolism of insulin (see "Special instructions", "Pharmacodynamics" and "Pharmacokinetics").

Liver failure. Tudzheo SoloStar® can be used in patients with hepatic insufficiency. It is recommended to carefully monitor the concentration of glucose in the blood, and the dose of insulin should be selected individually. In patients with hepatic insufficiency, the need for insulin may decrease due to a decrease in gluconeogenesis and a slowdown in the metabolism of insulin (see Pharmacodynamics, Pharmacokinetics and Specific Guidance).

Mode of application

Tudzheo SoloStar® is injected into the subcutaneous fat of the abdomen, shoulders or thighs. The injection sites should alternate with each new injection within the recommended areas for the administration of the drug.

Tudzheo SoloStar® is not intended for intravenous administration. The prolonged action of insulin glargine is observed only when it is injected into the subcutaneous fat. In / in the introduction of a usual SC dose can cause severe hypoglycemia. Tudzheo SoloStar® is not intended for administration with an insulin infusion pump.

TUDZHEO SoloStar® is a clear solution, not a suspension, so no resuspension is required before use. With the help of the Tudzheo SoloStar® syringe pen, doses of 1 to 80 units per injection can be administered in increments of 1 dose of ED:

- the counter of doses of the syringe-pen Tudzheo SoloStar® shows the amount of ED of Tudzheo SoloStar®, which will be introduced. The Tudzheo SoloStar® pen was specially developed for Tudzheo SoloStar®, so no additional dose recalculation is required;

- Tudzheo SoloStar® should never be removed from the syringe cartridge into the syringe (see "Special instructions");

- You can not reuse needles. Before each injection, a new sterile needle should be attached. Reuse of needles increases the risk of their blockage, which can lead to a lower dose or an overdose. In addition, the use of a new sterile needle for each injection minimizes the risk of contamination and infection;

- if the needle is blocked, the patient must follow the instructions in step 3 (see the Tudzheo SoloStar® Instruction Manual).

To avoid possible transmission of blood-borne diseases, insulin syringe pens should not be used by more than one patient, even if the needle is replaced.

For the correct use of the Tudzheo SoloStar® syringe pen, see the Tudzheo SoloStar® Instruction Manual for the syringe pen. To exclude the possibility of erroneous (accidental) introduction of another type of insulin in place of Tudzheo SoloStar®, always check the label on the syringe pen before each injection (on the label, the Tudzheo SoloStar® syringe concentration "300 U / ml" is highlighted by a honey-gold background ).

The period of use of the drug in a disposable syringe-pen Tudzheo SoloStar® after the first use is 4 weeks, when stored in a dark place. It is recommended that the date of its first use be indicated on the syringe-stick label.

Instructions for the use of the TUDZHEO SoloStar® syringe pen (insulin glargine 300 U / ml)

The Tudzheo SoloStar® pen contains insulin glargine at a concentration of 300 U / ml.

1. Never reuse the needle. If the needle is reused, because the needle may become clogged, the patient may not receive the dose required (lower dose) or get too much (overdose).

2. Never use a syringe to remove insulin from a syringe pen. In this case, the patient can get too much insulin. The scale on most insulin syringes is intended only for non-concentrated insulin.

Important information

1. Do not use one syringe pen at the same time as other people, even if the needle is replaced. The patient can get a serious infection from other people or give them a serious infection, transmitted through the blood.

2. Never use a syringe pen if it is damaged or the patient is not sure that it is working.

3. Always conduct a safety test.

4. Always carry a spare syringe pen and spare needles in case they are lost or become defective.

5. Before using the syringe pen, ask your health care provider how to properly administer the SC injection.

6. If the patient has visual problems, he may need the help of others who are able to follow all the recommendations of this instruction manual for the use of the Tudzheo SoloStar® syringe pen.

Before using the syringe pen, read the entire instructions. If the patient does not follow all the recommendations, he can get either too much or too little insulin.

The patient will additionally need: a new sterile needle, an alcohol-soaked tissue, a puncture resistant container for used needles and syringes.

Indication of sites for injections

Acquaintance with a syringe pen

1 - a cap of a syringe-handle;

2 - rubber membrane;

3 - scale of insulin;

4 - the name of insulin;

5 - the selector of doses;

6 - dose button;

7 - dose indicator;

8 - window of the dose indicator;

9 - the piston *;

10 - the cartridge holder.

* The patient may not see the plunger until several doses are given.

Step 1. Checking the syringe pen

Remove the new syringe pen from the refrigerator, at least 1 hour before the injection. The introduction of cold insulin is more painful.

A. Check the insulin name and expiration date on the label of this syringe pen.

Make sure that the patient has the right (needed) insulin.

Never use a syringe pen after the expiration date.

B. Remove the cap from the syringe pen.

C. Check the transparency of insulin.

Do not use a syringe pen if the insulin is cloudy, has a color or contains foreign particles.

D. Wipe the rubber membrane with a cloth moistened with ethyl alcohol.

If the patient has other syringe-pens, it is especially important to make sure that he took the right (desired) drug.

Step 2. Attaching a new needle

Always use a new sterile needle for each injection. This will help prevent clogging of the needle, contamination and infection. Always use BD Micro-Fine® Plus needles.

Take a new needle and remove the protective coating.

E. Hold the needle directly in front of the syringe pen and screw it onto the syringe pen until it stops. Do not apply excessive force when screwing the needle.

F. Remove the outer needle cap. Save it for later use.

G. Remove the inner cap from the needle and discard it

Step 3. Conducting a security test

Handling of needles. Care should be taken when handling needles - this will prevent needle damage and cross infection.

It is mandatory to conduct a safety test before each injection - it is carried out to check the correctness of the syringe handle operation and to avoid the obstruction of the needle, and also to ensure that the patient enters the correct dose of insulin.

H. Dial 3 units by rotating the dose selector until the dose indicator appears between numbers 2 and 4.

I. Press the dose button until it stops.

If a drop of insulin appears at the tip of the needle, this indicates that the syringe pen works correctly.

If insulin is not shown at the tip of the needle:

- the patient may need to repeat this step up to 3 times before insulin appears. If insulin does not appear at the tip of the needle and after the third repetition of this step, then perhaps the needle is impassable; Then replace the needle (see Steps 6 and 2) and then repeat the safety test (Step 3);

- Do not use a syringe pen if insulin does not show up at the tip of the needle. Use a new syringe pen;

- Never use a syringe to extract insulin from the Tudzheo SoloStar® pen.

If air bubbles are visible. The patient can see air bubbles in the insulin. It's normal, they will not hurt him.

Step 4. Dose Set

Never take a dose and do not press the dose button without a needle attached. This can damage the syringe pen.

J. Make sure that the needle is attached and the dose is set to "0"

K. Rotate the dose selector until the dose indicator is in line with the patient's desired dose.

If the patient has turned the dose selector beyond the required dose, you can turn it back.

If there is not enough ED in the syringe pen for the proper dose, the patient can inject it in 2 injections, using a new syringe pen for the 2nd injection, or immediately use a new syringe pen for the entire dose.

How to read the indicator of the dose indicator window. Even numbers of the number of units are displayed opposite the dose indicator:

Odd numbers of the number of units are displayed on the line between even numbers.

Units of insulin in the syringe-pen. The syringe pen contains a total of 450 units of insulin. The patient can take doses from 1 to 80 units in steps of 1 unit. Each syringe pen contains more than one dose.

The patient can approximately determine the amount of remaining insulin IU by the location of the piston on the insulin scale.

Step 5. Dosing Introduction

If difficulties arise when you press the dose button, do not use force, because This can damage the syringe pen (see the section below, which describes the patient's actions in this situation).

L. Choose a site for injection, as shown in the figure above.

M. Insert the needle into the skin, as was shown by the medical worker. Do not touch the dose button

N. Place your thumb on the dose button. Then press it all the way and hold it in this position. Do not press the button at an angle - the thumb can block the rotation of the dose selector.

O. Continue to press the dose button, and when in the dose window the patient sees "0", slowly count to five. This will ensure the introduction of a full dose.

P. After holding the dose entry button and counting to five, release the dose button. Then remove the needle from the skin. If there are difficulties when pressing the dose button: change the needle (see Steps 6 and 2), then conduct a safety test (see Step 3). If difficulties persist when you press the dose button, take A new syringe pen.

Step 6. Removing the needle

Care should be taken when handling the needle - this will prevent needle damage and cross infection.

Never again put an inner needle cap on the needle.

Q. Take the wide end of the outer needle cap with two fingers. Hold the needle straight and insert it into the outer needle cap. Then press the cap tightly. If the needle is inserted into the cap at an angle, it can pierce it.

R. Firmly grasp the wide part of the outer needle cap. Turn the syringe handle several times with the other hand to remove the needle. If the needle is not removed the first time, try again.

S. Discard the used needle in a tight (puncture-resistant) container that should be carefully closed and discarded after filling in accordance with the instructions of the medical professional.

T. Close the syringe pen with its cap.

Do not put the syringe pen in the refrigerator.

Term of use

Use a syringe pen for 4 weeks after first use.

Storage of the syringe pen

Before first use. Store new syringe pens in the refrigerator at 2-8 ° C. Do not freeze the pen-syringe.

After first use. Store the syringe pen at a temperature below 30 ° C. Never put the syringe handle back in the refrigerator. Never store a syringe pen with attached needle. Keep the syringe pen closed with a cap.

Handling of the TUDZHEO SOLO STAR® syringe pen. Handle with the syringe-handle with caution.

Do not drop the syringe pen or avoid its impact on hard surfaces.

If the patient thinks that the pen syringe may have been damaged without trying to repair it, use a new syringe pen.

Protect the syringe handle from dust and dirt. You can clean the outside of the syringe pen by wiping it with a damp cloth. Do not soak, wash or lubricate the syringe pen - this can damage it.

Disposal of the syringe pen

Remove the needle before discarding the syringe pen.

Dispose used used syringes according to the instructions of the health care provider.

Overdose

Symptoms: an overdose of insulin (an excess of insulin relative to food intake, energy consumption, or both) can lead to a severe and sometimes prolonged and life-threatening patient with hypoglycemia.

Treatment: episodes of moderate-to-moderate hypoglycemia are usually stopped by ingesting rapidly digested carbohydrates. It may be necessary to change the dosage regimen of the drug, diet or physical activity.

Episodes of more severe hypoglycemia, manifested by coma, convulsions or neurological disorders, can be stopped in / m or by / by the administration of glucagon or iv by the administration of a concentrated solution of dextrose (glucose). It may be necessary to take carbohydrates for a long time and observe the specialist, since After a visible clinical improvement, a relapse of hypoglycemia is possible.

special instructions

Patients should have the skills of self-monitoring of diabetes, including monitoring of blood glucose concentration, and adhere to the correct technique of carrying out injections and be able to curtail the development of hypoglycemia and hyperglycemia. Insulin therapy requires constant alertness regarding the possibility of developing hyperglycemia or hypoglycemia.

In case of insufficient control of blood glucose concentration, and if there is a tendency to develop hypo- or hyperglycemia, before proceeding with correcting the dosage regimen, it is necessary to check the accuracy of the prescribed treatment regimen, adherence to the directions for the injection site, the correct technique of subcutaneous injection and Handling of the SoloStar® syringe pen, and also consider the possibility of all other factors capable of causing such a condition.

Hypoglycaemia

The time of development of hypoglycemia depends on the profile of the action of the insulin used and can thus change when the treatment regimen is changed. Special care should be taken to intensify monitoring of blood glucose concentration when the drug is used in patients in whom episodes of hypoglycemia may be of particular clinical importance, such as patients with severe stenosis of the coronary arteries or cerebral vessels (risk of cardiac and cerebral complications of hypoglycemia), and Also patients with proliferative retinopathy, especially if they do not receive photocoagulation treatment (risk of transient loss of vision following hypoglycemia). As with any type of insulin, in some states, symptoms-precursors of hypoglycemia may change, become less pronounced or absent.

These include:

- a marked improvement in glycemic control;

- gradual development of hypoglycemia;

- elderly age;

- the presence of autonomic neuropathy;

- a long history of diabetes mellitus;

- the presence of mental disorders;

- simultaneous use of insulin glargine with some other drugs (see "Interaction").

Such situations can lead to the development of severe hypoglycemia (with possible loss of consciousness) before the patient realizes that he is developing hypoglycemia.

It should be taken into account that the prolonged action of Tudzheo SoloStar® with its p / c introduction can delay the patient's exit from the state of hypoglycemia.

In case normal or reduced rates of glycosylated Hb are observed, it is necessary to consider the possibility of developing recurrent unrecognized episodes of hypoglycemia (especially at night).

Patient compliance with the dosing regimen and diet, proper insulin administration and knowledge of hypoglycemia precursors contribute to a significant reduction in the risk of developing hypoglycemia.

Factors that increase the tendency to hypoglycemia, in the presence of which a particularly careful observation is required and correction of the insulin dose may be necessary:

- change of place of insulin administration;

- Increased sensitivity to insulin (for example, when stress factors are eliminated);

- unusual, increased or prolonged physical activity;

- intercurrent diseases, accompanied by vomiting, diarrhea;

- Inadequate intake of food;

- consumption of ethanol;

- Some uncompensated endocrine disorders (such as hypothyroidism, insufficiency of the anterior lobe of the pituitary gland or insufficiency of the adrenal cortex);

- simultaneous use of insulin glargine with some other drugs (see "Interaction").

In patients with renal insufficiency, the need for insulin can be reduced by slowing the metabolism of insulin (see "Pharmacodynamics", "Pharmacokinetics" and "Method of administration and dose"). In elderly patients, a progressive impairment of kidney function can lead to a steady decrease in insulin requirements (see Pharmacodynamics, Pharmacokinetics, and Dosage and Administration).

In patients with severe hepatic insufficiency, the need for insulin can be reduced due to a decrease in the ability to gluconeogenesis and slowing down the metabolism of insulin (see Pharmacodynamics, Pharmacokinetics and Dosage and Administration).

Hypoglycemia as a whole can be eliminated by the immediate administration of rapidly digestible carbohydrates. Since the initial actions to correct hypoglycemia should be carried out immediately, patients should always have at least 20 grams of fast-digestible carbohydrates with them.

Intercurrent diseases

With intercurrent diseases, a more intensive control of the concentration of glucose in the blood is required. In many cases, the analysis of the presence of ketone bodies in the urine is shown, and often a correction of the insulin dosage regimen is required. When an intercurrent disease occurs, the need for insulin often rises. Patients with type 1 diabetes should continue to receive carbohydrates on a regular basis, even if they are able to eat only small amounts or not at all or in case of vomiting; Patients with type 1 diabetes mellitus should never completely miss the introduction of insulin.

Combination of insulin glargine with pioglitazone

When pioglitazone was used in combination with insulin, cases of heart failure were reported, especially in patients at risk of developing heart failure. This information should be taken into account when considering the use of a combination of pioglitazone with Tudzheo SoloStar®. When using this combination, patients should be observed for signs and symptoms of heart failure, such as weight gain, edema. With the appearance or weighting of cardiac symptoms, the use of pioglitazone should be discontinued.

Prevention of errors with the introduction of insulin preparations

In order not to confuse Tudzheo SoloStar® with other insulins, always check the label on the syringe pen before each injection. It has been reported that other insulins, in particular short-acting insulins, were accidentally mistakenly introduced, instead of long-acting insulins.

To avoid dosing errors and a possible overdose, patients should never use a syringe to remove the Tudzheo® drug from the SoloStar® syringe pen (see "Dosing and Administration", "Overdose").

As with the use of other insulin syringes, patients should visually check the number of dialed dose units in the dose indicator box on the syringe pen. Blind or visually impaired patients should receive assistance from other people with good eyesight and who can use the Tudzheo SoloStar® pen.

Recommendations for the storage of the Tugo SoloStar® pen

When storing Tudzheo SoloStar® in the refrigerator (unopened / prior to use), make sure that the syringe pen packs do not directly touch the freezer compartment or frozen food. The drug should not be frozen. If the insulin has been frozen, it can not be used, and the syringe-pen should be disposed of.

Used SoloStar® handles should be stored at a temperature not exceeding 30 ° C, protected from light and heat.

Impact on the ability to drive vehicles and engage in other potentially hazardous activities. The ability of patients to concentrate attention and speed of psychomotor reactions can be disturbed, for example, as a result of the development of hypoglycemia or hyperglycemia, as well as as a result of visual impairment. This can be a risk in situations where these capabilities are particularly important (for example, driving or working with other mechanisms). Patients are advised to take precautions to avoid the development of hypoglycemia during the management of vehicles. This is especially important for those who have mild or no symptoms that are precursors of developing hypoglycemia, or for patients with frequent episodes of hypoglycemia. These features of the patient should be taken into account when deciding whether to manage the vehicle.

Form of issue

Solution for subcutaneous administration, 300 U / ml. For 1.5 ml of the preparation in a cartridge of colorless glass (type I). The cartridge is sealed on one side with a cork and crimped with an aluminum cap, on the other hand - by a plunger. The cartridge is mounted in a disposable syringe pen SoloStar®. 1, 3 or 5 SoloStar® syringes are placed in a cardboard box.

Terms of leave from pharmacies

On prescription.

Storage conditions

In the dark place at a temperature of 2-8 ° C (do not freeze).

Keep out of the reach of children.

Shelf life

2.5 years.

Do not use after the expiry date printed on the package.