Instruction for use: Levemir Penfill

ATX Code A10AE05 Insulin detemir

Active substance Insulin detemir

Pharmacological group

Hypoglycemic agent - an insulin analogue of human long-acting [Insulin]

Nosological classification (ICD-10)Z31.1 Artificial insemination

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 detemir 100 ED (14.2 mg)

1 cartridge contains 3 ml of a solution equivalent to 300 U

1 ED contains 0.142 mg of salt-free insulin detemir, which corresponds to one unit of human insulin (ME)

Excipients: glycerol - 16 mg; Phenol 1.8 mg; Meta-cresol - 2.06 mg; Zinc - 65.4 μg (in the form of zinc acetate); Sodium hydrogen phosphate dihydrate 0.89 mg; Sodium chloride - 1,17 mg; Hydrochloric acid or sodium hydroxide - q.s .; Water for injection - up to 1 ml

Levemir® FlexPen®

Solution for subcutaneous administration 1 ml

active substance:

Insulin detemir 100 ED (14.2 mg)

Auxiliary substances: glycerol - 16 mg; Phenol 1.8 mg; Meta-cresol - 2.06 mg; Zinc - 65.4 μg (in the form of zinc acetate); Sodium hydrogen phosphate dihydrate 0.89 mg; Sodium chloride - 1,17 mg; Hydrochloric acid or sodium hydroxide - q.s .; Water for injection - up to 1 ml

1 syringe-pen contains 3 ml of a solution equivalent to 300 units

1 ED contains 0.142 mg of salt-free insulin detemir, which corresponds to 1 unit of human insulin (ME)

Description of dosage form

A clear, colorless solution.

pharmachologic effect

Pharmacological action - hypoglycemic.

Pharmacodynamics

Levemir® Penfill® and Levemir® FlexPix® are produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain. It is a soluble basal analogue of human long-acting insulin with a flat action profile. The action profile of Levemir® Penfill® and Levemir® FlexPix® is significantly less variable than isophane-insulin and insulin glargine.

The prolonged action of Levemir® Penfill® and Levemir® FlexPen® is due to the pronounced self-association of insulin detemir molecules at the injection site and the binding of the drug molecules to albumin by bonding to the fatty acid side chain. Insulin detemir is slower than isophane-insulin to peripheral target tissues. These combined delayed distribution mechanisms provide a more reproducible absorption profile and the effects of Levemir® Penfill® and Lewemer® FlexPix® versus isophane-insulin.

For doses of 0.2-0.4 units / kg, 50% of the maximum effect of the drug occurs between 3-4 and 14 hours after administration. The duration of action is up to 24 hours, depending on the dose, which provides the possibility of a single and twice daily administration. With a double injection of Css the drug is achieved after the introduction of 2-3 doses of the drug.

After SC administration, a pharmacodynamic response was observed proportional to the dose administered (maximum effect, duration of action, total effect).

In long-term studies, low plasma fasting plasma glucose variability was shown on a daily basis when treated with Levemir® Penfill® or Levemir® FlexPix®, in contrast to isophane insulin.

In long-term studies in patients with type 2 diabetes mellitus who received basal insulin therapy in combination with oral hypoglycemic drugs, it was demonstrated that glycemic control (in terms of glycosylated hemoglobin - HbA1c) against the background of Levemir® Penfill® or Levemir® FlexPan® treatment was Comparable to that in the treatment of isophane-insulin and insulin glargine with low body weight gain

In studies, the use of combination therapy with Levemir® Penfill® or Levemir® FlexPen® and oral hypoglycemic drugs led to a reduction in the risk of developing mild nocturnal hypoglycemia by 61-65% compared with isofan-insulin.

An open, randomized clinical trial was conducted with patients with type 2 diabetes mellitus who did not achieve glycemic targets against oral hypoglycemic therapy. The study began with a 12-week preparatory period, during which patients received combined therapy with liraglutide in combination with metformin, and against which 61% of patients reached HbA1c <7%. 39% of patients who did not achieve the target glycemia values with combination therapy with liraglutide and metformin were randomized to 2 therapeutic groups for further treatment. Patients of one of the therapeutic groups, in addition to the therapy of liraglutide with metformin, were prescribed Levemir® Penfill® / Levemir® FlexPen® in a daily single dose; Patients continued to receive liraglutide in combination with metformin for the next 52 weeks. During this period, the therapeutic group receiving additionally to the therapy of liraglutide with metformin a daily single injection of Levemir Penfill® / Lewemer® FlexPix® showed a further decrease in HbA1c from baseline of 7.6% to 7.1% at the end of the 52-week Period, in the absence of episodes of severe hypoglycemia. When adding a dose of Levemir® Penfill® / Levemir® FlexPix® to liraglutide therapy, the latter's advantage was maintained with respect to statistically significant weight loss in patients

In long-term studies (≥6 months) in patients with type 1 diabetes mellitus, the fasting plasma glucose concentration was better when treated with Levemir® Penfill® / Levemir® FlexPen® compared to isofan-insulin in basal bolus therapy . Glycemic control (HbA1c) against the background of Levemir® Penfill® / Levemir® FlexPen® therapy was comparable to that for isophane-insulin therapy, but with a lower risk of developing nocturnal hypoglycemia and a lack of weight gain with the use of Levemir® Penfill® / Levemir® FlexPlex®.

The results of clinical studies evaluating the basal-bolus regimen of insulin therapy indicate a comparable incidence of hypoglycemia as a whole against the background of Levemir® Penfill® / Levemir® FlexPen® and isophane-insulin therapy. Analysis of the development of nocturnal hypoglycemia in patients with type 1 diabetes mellitus demonstrated a significantly lower incidence of light nocturnal hypoglycemia with the use of Levemir® Penfill® / Levemir® FlexPen® (when the patient can independently eliminate hypoglycemia and hypoglycemia is confirmed by measuring the glucose concentration in the capillary Blood - less than 2.8 mmol / l or glucose in the blood plasma - less than 3.1 mmol / l) compared with that when using isophane-insulin; And there was no difference in the incidence of episodes of light nocturnal hypoglycemia in patients with type 2 diabetes mellitus between the two study drugs. The profile of nighttime glycemia is more flat and smooth in Levemir Penfill® / Lewemer® FlexPen® compared to isophane-insulin, Which is reflected in a lower risk of developing nocturnal hypoglycemia. With the use of Levemir® Penfill® / Levemir® FlexPen®, antibody production was observed. However, this fact does not affect glycemic control.

Pregnancy

A randomized, controlled clinical trial of 310 pregnant women with type 1 diabetes mellitus evaluated the efficacy and safety of Levemir® Penfill® / Levemir® FlexPlex® in a basal-bolus regimen (152 patients) compared with isophane-insulin (158 Patients), in combination with insulin aspart used as prandial insulin.

The results of the study showed that in patients treated with Levemir® Penfill® / Levemir® FlexPlex®, the decrease in HbA1c at the 36th week of pregnancy was similar to that of the group receiving isofan-insulin. A group of patients treated with Levemir® Penfill® / Levemir® FlexPen® and a group receiving isophane-insulin therapy showed similarity throughout the gestation period for the overall profile of HbA1c.

The target level of HbA1c ≤6% at the 24th and 36th weeks of gestation was achieved in 41% of patients in the levemir® Penfill® / Levemir® FlexPen® therapy group and 32% in the isofan-insulin therapy group.

Fasting glucose concentrations at gestational age 24 and 36 weeks were statistically significantly lower in that group of women who were taking Levemir® Penfill® / Levemir® FlexPen®, compared to the group receiving isophane-insulin therapy. During the entire gestation period, there were no statistically significant differences between the patients who received the Levemir® Penphyl® / Levemir® FlexPen® and isophane-insulin, according to the incidence of episodes of hypoglycemia.

Both groups of pregnant women treated with Levemir® Penfill® / Levemir® FlexPen® and isofan-insulin showed similar results for the incidence of adverse events during the entire gestation period; However, it was found that the incidence of serious adverse events in women throughout the gestation period was quantitative (61 (40%) vs 49 (31%), in infants during the intrauterine growth period and after birth (36 (24%) vs 32 (20%) was higher in the Levemir® Penfill® / Levemir® FlexPen® treatment group compared to the isofan-insulin therapy group.

The number of live-born children from mothers who became pregnant after they were randomly assigned to therapeutic groups for treatment with one of the drugs studied was 50 (83%) in the Levemir® Penfill® / Levemir® FlexPen® treatment group and 55 (89% ) In the isofan-insulin treatment group. The number of children born with congenital malformations was 4 (5%) in the Levemir® Penfill® / Levemir® FlexPen® treatment group and 11 (7%) in the isofan-insulin treatment group. Of these, serious congenital malformations were noted in 3 (4%) children in the Levemir® Penfill® / Levemir® FlexPen® treatment group and 3 (2%) in the isofan-insulin treatment group.

Children and teens

The efficacy and safety of the Levemir® Penfill® / Levemir® FlexPen® in children was studied in 2 controlled clinical trials of 12 months with the participation of adolescents and children over the age of 2 years with Type 1 diabetes mellitus (total 694 patients); One of these studies included a total of 82 children with type 1 diabetes mellitus in the age group 2 to 5 years. The results of these studies demonstrated that the glycemic control (HbA1c) against the background of Levemir® Penfill® / Levemir® FlexPen® therapy was comparable to that of isophane-insulin therapy when administered in basal bolus therapy. In addition, there was a lower risk of developing nocturnal hypoglycemia (based on plasma glucose values measured by patients alone) and the absence of weight gain (standard deviation for body weight adjusted according to the sex and age of the patient) against the background of Levemir® Penfill® / Levemir® FlexPen® compared to the use of isophane-insulin. One of the clinical trials was extended for a further 12 months (a total of 24 months clinical data were obtained) in order to obtain a more complete database for assessing the formation of antibodies in patients with long-term treatment with Levemir® Penfill® / Levemir® FlexPen®.

The results obtained in the course of the study indicate that during the first year of treatment, an increase in the titer of antibodies to insulin detemir occurred with the use of Levemir® Penfill® / Levemir® FlexPix®; But by the end of the second year of treatment, the antibody titer to Levemir Penfill® / Lewemer® FlexPix® was reduced in patients to slightly above baseline at the time of initiation of Levemir® Penfill® / Levemir® FlexPan®. Thus, it has been proved that the formation of antibodies in patients with diabetes mellitus against the background of treatment with Levemir® Penfill® / Levemir® FlexPix® does not adversely affect the level of glycemic control and the dose of insulin detemir.

Pharmacokinetics

Absorption

Cmax in blood plasma is achieved 6-8 hours after administration.

With a double daily regimen of administration of Css drug in blood plasma is achieved after 2-3 injections.

The intra-individual variability of absorption is lower in the Levemir® Penfill® / Levemir® FlexPen® than in other basal insulin preparations.

Clinically significant gender differences in the pharmacokinetics of the Levemir® Penfill® / Levemir® FlexPen® preparation were not identified.

Distribution

The median Vd of Levemir® Penfill® / Levemir® FlexPix® (approximately 0.1 l / kg) indicates that a high proportion of insulin detemir circulates in the blood.

Metabolism

Inactivation of the Levemir® Penphyl® / Levemir® FlexPix® is similar to that of human insulin preparations; All formed metabolites are inactive.

The results of studies of protein binding in vitro and in vivo indicate the absence of clinically significant interactions between insulin detemir and fatty acids or other preparations that bind to proteins.

Excretion

Terminal T1 / 2 after SC injection is determined by the degree of absorption from the subcutaneous tissue and is 5-7 hours depending on the dose.

Linearity

With n / to the introduction of concentration in the blood plasma were proportional to the administered dose (Cmax, the degree of absorption).

There was no pharmacokinetic or pharmacodynamic interaction between liraglutide and Levemir® Penfill® / Lewemer® FlexPen®, in equilibrium, while concomitantly administered to patients with type 2 diabetes mellitus Levemir® Penfill® / Levemir® FlexPen® in a single dose of 0.5 U / Kg and liraglutide in a dose of 1.8 mg.

Special patient groups

The pharmacokinetic properties of the Levemir® Penfill® / Levemir® FlexPen® preparation were studied in children (6-12 years) and adolescents (13-17 years) and compared with pharmacokinetic properties in adults with type 1 diabetes mellitus. No differences were found.

Clinically significant differences in the pharmacokinetics of the Levemir® Penfill® / Levemir® FlexPen® between elderly and young patients or between patients with impaired renal and hepatic function and healthy patients have not been identified.

Pre-clinical safety data

In vitro studies in the human cell line, including studies on binding to insulin receptors and IGF-1, have shown that insulin detemir has a low affinity for both receptors and has little effect on cell growth as compared to human insulin. Preclinical data based on routine studies of pharmacological safety, toxicity of repeated doses, genotoxicity, carcinogenic potential, toxic effect on reproductive function, did not reveal any danger to humans.

Indications

Diabetes mellitus in adults, adolescents and children over 2 years.

Contraindications

Increased individual sensitivity to insulin detemir or any of the components of the drug;

Children under 2 years of age (no clinical studies have been performed in this group of patients).

pregnancy and lactation

When using Levemir® Penfill® / Levemir® FlexPen® during pregnancy, it is necessary to consider how far the benefits of its use outweigh the possible risks.

One of the randomized controlled clinical trials involving pregnant women with type 1 diabetes mellitus, which examined the efficacy and safety of the combined Levemir® Penfill® / Levemir® FlexPen® with insulin aspart (152 pregnancies) versus isophan-insulin therapy in The combination with insulin aspart (158 pregnant women) did not reveal a difference in the overall safety profile during pregnancy, in pregnancy outcomes or in the effects on fetus and newborn health (see Pharmacodynamics, Pharmacokinetics ").

Additional data on the efficacy and safety of Levemir® Penfill® / Levemir® FlexPen®, obtained from approximately 300 pregnant women during post-marketing use, indicate that there are no undesirable side effects of insulin detemir, leading to congenital malformations and malformative or feto / neonatal Toxicity.

Studies of reproductive function in animals have not revealed a toxic effect of the drug on the reproductive system (see "Pharmacodynamics", "Pharmacokinetics").

In general, careful monitoring of pregnant women with diabetes during their entire pregnancy, as well as in the planning of pregnancy, is necessary. The need for insulin in the first trimester of pregnancy is usually reduced, then in the II and III trimesters increases. Shortly after birth, the need for insulin quickly returns to the level that was before pregnancy.

It is not known whether insulin detemir is excreted in breast milk. It is assumed that insulin detemir does not affect the metabolic reactions in the body of newborns / infants during the period of breastfeeding, since it belongs to a group of peptides that are easily digested in the digestive tract by amino acids and are absorbed by the body.

Nursing women may need to adjust their insulin dose and diet.

Side effects

Adverse reactions observed in patients using Levemir® mainly develop due to the pharmacological effect of insulin. The proportion of patients receiving treatment and who are expected to develop adverse reactions is estimated as 12%.

The most common adverse reaction that develops during treatment with Levemir® is hypoglycemia (see section below).

It is known from clinical studies that severe hypoglycemia requiring third-party intervention develops in approximately 6% of patients receiving Levemir®.

Reactions at the site of administration may occur more frequently with Levemir® than with human insulin preparations. These reactions include pain, redness, hives, inflammation, bruising, swelling and itching at the injection site. Most of the reactions at the sites of administration are insignificant and transient in nature, i.e. Usually disappear when the treatment is continued for several days to several weeks.

At the initial stage of insulin therapy, refractive disorders and edema can occur. These symptoms are usually transient. Rapid improvement in glycemic control can lead to a state of acute pain neuropathy, which is usually reversible. Intensification of insulin therapy with a sharp improvement in carbohydrate metabolism control may lead to a temporary deterioration in the state of diabetic retinopathy, while a prolonged improvement in glycemic control reduces the risk of progression of diabetic retinopathy.

The list of adverse reactions is presented in the table.

All of the adverse reactions presented below, based on data from clinical trials, are grouped according to the frequency of development according to 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 / 10000 to <1/1000); Very rarely (<1/10000) and unknown (can not be estimated based on available data)

Description of individual adverse reactions

Allergic reactions, potentially allergic reactions, urticaria, skin rash, rashes on the skin. When levemir® was used in the basal-bolus regimen of therapy, the development of allergic reactions, potentially allergic reactions, urticaria, skin rashes and skin rashes was noted infrequently. However, data from 3 clinical studies showed frequent development of adverse reactions with Levemir® as part of combination therapy with other oral hypoglycemic drugs (2.2% of allergic reactions and potentially allergic reactions).

Anaphylactic reactions. Reactions of generalized hypersensitivity (including generalized skin rash, itching, sweating, gastrointestinal disorders, angioedema, difficulty breathing, heart palpitations, decreased blood pressure) are very rare, but are potentially life threatening.

Hypoglycemia. Hypoglycemia is the most common adverse reaction. It can develop if the dose of insulin is too high in relation to the need for insulin. Severe hypoglycemia can lead to loss of consciousness and / or convulsions, temporary or irreversible impairment of brain function or even death. Symptoms of hypoglycemia tend to develop suddenly. They include cold sweat, pale skin, increased fatigue, nervousness or tremor, anxiety, unusual fatigue or weakness, impaired orientation, decreased concentration, drowsiness, severe hunger, visual impairment, headache, nausea, palpitations.

Lipodystrophy. Lipodystrophy (including lipohypertrophy, lipoatrophy) can develop at the injection site. Adherence to the rules for changing the injection site within one area can help reduce the risk of developing this adverse reaction.

Interaction

There are a number of drugs that affect the need for insulin.

Hypoglycemic action of insulin increases oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, nonselective beta adrenoblockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, salicylates.

The hypoglycemic effect of insulin is weakened by oral contraceptives, GCS, iodine-containing thyroid hormones, somatropin, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, BCC, diazoxide, morphine, phenytoin, nicotine.

Octreotide / lanreotide can both increase and decrease the body's need for insulin.

Beta-adrenoblockers can mask symptoms of hypoglycemia and delay recovery after hypoglycemia.

Alcohol can both enhance and reduce the hypoglycemic effect of insulin.

Incompatibility. Some medicines, for example those containing thiol or sulphite groups, may cause the destruction of insulin detemir upon addition to the preparation of Levemir® Penphyl® / Levemir® FlexPix®. Levemir® Penfill® / Levemir® FlexPlex® should not be added to infusion solutions. This drug should not be mixed with other drugs.

Dosing and Administration

PC.

The dose of Levemir® Penfill® / Levemir® FlexPix® should be selected individually in each case, based on the patient's needs.

Based on the results of the studies, the following are recommendations for titrating doses

If Levemir® Penfill® / Levemir® FlexPlex® is used as part of the basal-bolus regimen, it should be administered 1 or 2 times a day, based on the patient's need.

Patients who require the use of the drug twice a day for optimal glycemic control can enter the evening dose either during supper or at bedtime. Dose adjustment may be necessary if the patient's physical activity is increased, his usual diet changes or if he has a concomitant disease.

The Levemir® Penfill® / Levemir® FlexPen® medicinal preparation can be used both as monotherapy and in combination with bolus insulin. It can also be used in combination with oral hypoglycemic drugs, as well as in addition to existing therapy with liraglutide.

In combination with oral hypoglycemic agents or in addition to liraglutide, it is recommended to use Levemir® Penphyl® / Levemir® FlexPlex® once a day, starting at a dose of 10 U or 0.1-0.2 U / kg. The Levemir® Penfill® / Levemir® FlexPix® medicinal preparation can be administered at any time convenient for the patient during the day, however, after determining the time of daily injection, the prescribed injection regimen should be adhered to.

Levemir® Penfill® / Levemir® FlexPix® is intended for use only for administration. Leuemir® Penfill® / Levemir® FlexPix® should not be administered iv. This can lead to severe hypoglycemia. Also, I / m administration of the drug should be avoided. Levemir® Penfill® / Levemir® FlexPix® is not intended for use in insulin pumps.

Levemir® Penfill® / Levemir® FlexPlex® is injected into the thigh, anterior abdominal wall, shoulder, deltoid or gluteal region. The injection sites should be regularly changed even when administered in the same area to reduce the risk of developing lipodystrophy. As with other insulin preparations, the duration of action depends on the dose, place of administration, intensity of blood flow, temperature and level of physical activity.

Special patient groups

As with the use of other insulin preparations, elderly patients and patients with renal or hepatic insufficiency should more closely monitor the concentration of glucose in the blood and adjust the dose of insulin detemir individually.

Children and teenagers. Efficacy and safety of Levemir® Penfill® / Levemir® FlexPlex® in adolescents and children over 2 years of age has been confirmed in clinical trials of up to 12 months.

Translation from other insulin preparations. Transfers from insulin medications of medium duration and prolonged insulin preparations to the Levemir® Penfill® / Levemir® FlexPen® preparation may require adjustment of the dose and timing of administration.

As with the use of other insulin preparations, careful monitoring of blood glucose concentration during the transfer and in the first weeks of the appointment of a new drug is recommended.

It may be necessary to correct concomitant hypoglycemic therapy (dose and time of administration of short-acting insulin preparations or a dose of oral hypoglycemic drugs).

Overdose

A certain dose required for an insulin overdose has not been established, however hypoglycemia can develop gradually if a very high dose has been administered for a particular patient.

Treatment: mild hypoglycemia, the patient can eliminate himself by taking glucose, sugar or carbohydrate-rich foods. Therefore, patients with diabetes are encouraged to always carry sugar, sweets, cookies or sweet fruit juice.

In case of severe hypoglycemia, when the patient is unconscious, 0.5 to 1 mg of glucagon should be injected in / m or s / c (a trained person can inject) or / in a solution of dextrose (glucose) (can be administered only by a medical professional) . It is also necessary in / dextrose administered if after 10-15 min after administration of glucagon patient does not regain consciousness. After recovery of consciousness the patient is advised to take food rich in carbohydrates, for the prevention of relapse of hypoglycaemia.

special instructions

Levemir® Penfill® / Levemir® FlexPen® is a soluble basal analogue of insulin with prolonged action (up to 24 hours).

Unlike other insulin preparations, the baseline bolus therapy with the Levemir® Penfill® / Levemir® FlexPen® does not result in an increase in body weight.

Levemir® Penfill® / Levemir® FlexPen® medication provides less weight gain than isophane-insulin and insulin glargine.

The lower risk of nocturnal hypoglycemia compared with isophane-insulin allows more intensive titration of the dose in order to achieve the target blood glucose in basal bolus therapy.

Compared to other insulins, in particular isophane-insulin, a lesser risk of episodes of mild nocturnal hypoglycemia allows a more intensive dose selection to achieve the blood glucose target in the treatment with Levemir® Penfill® / Levemir® FlexPen® in combination with oral hypoglycemic Preparations.

Levemir® Penfill® / Levemir® FlexPlex® provides better glycemic control (based on measuring fasting plasma glucose concentration) compared to isophane-insulin.

Before a long trip associated with the change of time zones, the patient should consult with his attending physician, as changing the time zone means that the patient should take food and inject insulin at another time.

Insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia or diabetic ketoacidosis. Typically, the first symptoms of hyperglycemia appear gradually, within a few hours or days. These symptoms include thirst, rapid urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, odor of acetone in the exhaled air. With type 1 diabetes mellitus, without appropriate treatment, hyperglycemia leads to the development of diabetic ketoacidosis and can lead to death.

Hypoglycemia can develop if the dose of insulin is too high in relation to the need for insulin, with skipping meals or unplanned intensive physical exertion.

After the compensation of carbohydrate metabolism, for example, with intensified insulin therapy, the symptoms typical for them-precursors of hypoglycemia may change in patients, which patients should be informed about. Common symptoms-precursors can disappear with prolonged course of diabetes.

Concomitant diseases, especially infectious and accompanied by fever, usually increase the body's need for insulin.

Correction of the dose of the drug may also be required if the patient has concomitant diseases of the kidneys, liver or disorders of the adrenal, pituitary or thyroid gland function.

Transfer of the patient from other insulin preparations. Transfer of the patient to a new type or preparation of insulin of another manufacturer should occur under strict medical supervision. If the concentration, producer, type, species (human, analog of human insulin) and / or the method of production thereof changes, dose adjustment may be required. Patients switching to treatment with Levemir® Penfill® / Levemir® FlexPlex® from another type of insulin may need a dose change compared to the doses of previously used insulin preparations. Dose adjustment can be performed with the administration of the first dose or during the first few weeks or months of treatment.

Reactions at the site of administration. As with other insulin preparations, reactions at the injection site can develop, which is manifested by pain, redness, hives, inflammation, bruises, swelling and itching. Regular injection site changes in the same anatomical area can reduce symptoms or prevent the development of a reaction. Reactions usually disappear for a few days to several weeks. In rare cases, reactions at the site of administration require discontinuation of treatment.

Simultaneous use of the preparations of the thiazolidinedione group and insulin preparations. Cases of CHF in the treatment of patients with thiazolidinediones in combination with insulin preparations have been reported, especially if such patients have risk factors for CHF. This fact should be taken into account when appointing patients combination therapy with thiazolidinediones and insulin preparations. When this combination therapy is prescribed, it is necessary to conduct medical examinations of patients to identify signs and symptoms of CHF, weight gain and edema. In case of worsening of symptoms of heart failure in patients, treatment with thiazolidinediones should be stopped.

Impact on the ability to drive vehicles and work with mechanisms. The ability of patients to concentrate and respond to the reaction may be compromised due to hypoglycemia, which can be dangerous in situations where these abilities are particularly needed (for example, when driving vehicles or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia in the management of vehicles and work with mechanisms. This is especially important for patients with a lack or decrease in the severity of symptoms-precursors of developing hypoglycemia or suffering from frequent episodes of hypoglycemia. In these cases, consideration should be given to the desirability of driving a vehicle or performing such work.

Form of issue

Levemir® Penfill®

3 ml in cartridges of glass 1 of hydrolytic class, sealed with discs of brombutyl rubber on one side and pistons of brombutyl rubber on the other. 5 cartridges per blister of PVC / aluminum foil. 1 blister in a cardboard box.

Levemir® FlexPen®

Solution for subcutaneous administration 100 U / ml. By 3 ml of the drug in the cartridges of glass I of hydrolytic class, sealed with bromobutyl rubber / polyisoprene stoppers on one side and pistons of bromobutyl rubber on the other side. The cartridge is sealed in a plastic multi-dose disposable syringe pen for multiple injections. For 5 plastic multi-dose disposable syringe pens for multiple injections are placed in a cardboard pack.

Terms of leave from pharmacies

On prescription.

Storage conditions

At a temperature of 2-8 ° C (in the refrigerator). But not next to the freezer. Do not freeze. Store the cartridges in a cardboard box to protect them from light. The drug should be protected from exposure to excessive heat and light. For opened cartridges: Do not store in the refrigerator. Store for 6 weeks at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf Life

30 months

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