Levemir FlexPen - instructions for use, doses, side effects, contraindications

Active substanceInsulin DetemirInsulin Detemir

Similar drugsTo uncover

Levemir® Penfield®

solution PC

Novo Nordisk A / S Denmark

Lewemir® FlexPen®

solution PC

Novo Nordisk A / S Denmark

Dosage form: & nbsphypodermic solution

Composition:

In 1 ml of the drug contains:

active substance: insulin detemir 100ED (14.2 mg);

Excipients: glycerol 16 mg, phenol 1.8 mg, metacresol 2.06 mg, zinc acetate 65.4 μg, sodium hydrogen phosphate dihydrate 0.89 mg, sodium chloride 1.17 mg, hydrochloric acid q.s. or sodium hydroxide q.s., water for injection up to 1 ml.

One syringe pen contains 3 ml of a solution equivalent to 300 units.

1 unit of insulin detemir contains 0.142 mg of insoluble insulin detemir.

1 unit of insulin detemir (ED) corresponds to 1 unit of human insulin (ME).

Description:

A clear, colorless solution.

Pharmacotherapeutic group:hypoglycemic agent - long-acting insulin analog

ATX: & nbsp

A.10.A.E.05 Insulin Detemir

Pharmacodynamics:

Lewemir® FlexPen® is produced by the biotechnology of recombinant DNA using a strain Saccharomyces cerevisiae. It is a soluble basal analogue of human long-acting insulin with a flat action profile.

The profile of the Levemir® FlexPene® activity is significantly less variable than isophane-insulin and insulin glargine.

The prolonged action of the Levemir® FlexPen® drug 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 side fatty acid chain. Insulin Detemir in comparison with isophane-insulin, it enters the peripheral target tissues more slowly. These combined delayed distribution mechanisms provide a more reproducible absorption profile and the action of the Levemir® FlexPen® preparation as compared to isophane-insulin.

For doses of 0.2-0.4 units / kg 50%, the maximum effect of the drug occurs in the interval from 3-4 hours to 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 administration, the equilibrium concentration of the drug is achieved after the administration of 2-3 doses of the drug.

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

Long-term studies have demonstrated low variabilityof plasma glucose concentration on an empty stomach day after day in the treatment of patients with the Levemir® FlexPen® preparation as opposed 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 - HbA₁_c) on the background of therapy with Lewemir® FlexPen®, was comparable to that for isophane-insulin and insulin treatment of glargine with low body weight gain (see Table 1).

Table 1. Change in body weight with insulin therapy

Duration research	Insulin Detemir once	Insulin Detemir Twice	Isofan- insulin	Insulin glargine
20 Weeks	+ 0.7 kg		+ 1.6 kg
26 weeks		+ 1.2 kg	+ 2.8 kg
52 weeks	+ 2.3 kg	+ 3.7 kg		+ 4.0 kg

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

An open randomized clinical trial was conducted with patients with type 2 diabetes mellitus who did not reach the target glycemia against oral hypoglycemic therapy.

The study began with a 12-week preparatory period, during which patients received combination therapy with liraglutide in combination with metformin, and against which 61% of patients achieved a HbA₁_c <7%. 39% of patients who did not achieve the target values of glycemia against the background of combined therapy with liraglutide with metformin were randomized to two therapeutic groups for further treatment. Patients of one of the therapeutic groups, in addition to the therapy of liraglutide with metformin, were prescribed Levemir® FlexPen® in a daily single dose; patients continued to receive another lyraglutide 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® FlexPen®, demonstrated a further decrease in the index HbA₁_c from the baseline of 7.6% to 7.1% at the end of the 52-week period, with no episodes of severe hypoglycemia. When adding a dose of Levemir® FlexPen® to liraglutide therapy, the latter's advantage was maintained with respect to a statistically significant decrease in body weight in patients, see Table 2.

Table 2.Data from clinical trials - therapy with Levemir ®, prescribed in addition to the combined scheme of treatment with liraglutide with metformin

	Weeks treatment	Patients, randomized for getting drug therapy Levemir® FlexPhen® in addition to therapy lyraglutide+ metformin N = 160	Patients, randomized for getting of therapy liraglutide + metformin N = 149	Coefficient authenticity changes P-value
Average change indicator values HbA₁c over with a starting point tests (%)	0-26	-0,51	+0,02	<0,0001
	0-52	-0,50	0,01	<0,0001
Ratio of patients, reached the target indicator values HbA_1C <7% (%)	0-26	43,1	16,8	<0,0001
	0-52	51,9	21,5	<0,0001
Change in body weight patients compared with indicators in the original test point (kg)	0-26	-0,16	-0,95	0,0283
	0-52	-0,05	-1,02	0,0416
Episodes of mild hypoglycemia (by the number of patient-years of exposure of the drug studied)	0-26	0,286	0,029	0,0037
	0-52	0,228	0,034	0,0011

In long-term studies (> 6 months) in patients with type 1 diabetes mellitus, the fasting plasma glucose concentration was better when treated with the drug Levemir® FlexPen® as compared to isophane-insulin prescribed in the basis / bolus therapy. Glycemic control (HbA₁_c) against the backdrop of therapy with Leveem® FlexPen® was comparable to that in the treatment of isophane-insulin,but with a lower risk of developing nocturnal hypoglycemia and a lack of weight gain when using Levemir® FlexPen®.

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® 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 mild hypoglycemia at night with the use of Levemir® FlexPen® (when the patient can independently eliminate hypoglycemia and when hypoglycemia is confirmed by measuring the glucose concentration in capillary blood less than 2 , 8 mmol / L or as a result of measuring the glucose concentration in the blood plasma less than 3.1 mmol / L), compared with that with isophane-insulin; while between the two drugs studied there were no differences in the incidence of episodes of light nocturnal hypoglycemia in patients with type 2 diabetes mellitus.

The profile of nocturnal glycemia is more flat and smooth in the Levemir® FlexPen® preparation compared with isophane-insulin, which is reflected in a lower risk of developing nocturnal hypoglycemia.

When levemir® FlexPen® was used, antibody production was observed. However, this fact does not affect glycemic control.

Pregnancy

A randomized controlled clinical trial involving 310 pregnant women with type 1 diabetes mellitus evaluated the efficacy and safety of Levemir® FlexPen® 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 the patients who received Levemir® FlexPen® received a similar decrease in the value of H compared with the group receiving isophane-insulinbA_1C at 36 weeks of gestation. A group of patients treated with Levemir® FlexPen® and a group receiving isophane-insulin therapy showed similarity throughout the gestation period in the overall profile HbA₁_c.

Target level HbA₁_c <6.0% at 24 and 36 weeks of gestation was achieved in 41% of patients in the levemir® FlexPen® therapy group and in 32% of patients in the isofan-insulin therapy group.

Fasting glucose at gestational age 24 and 36 weeks was statistically significantly lower in that group of women who were taking Levemir® FlexPen®, compared to the group receiving isofan-insulin therapy.

During the entire period of pregnancy, there were no statistically significant differences between the patients who received the Levemir® FlexPen® and isophane-insulin, according to the incidence of episodes of hypoglycemia.

Both groups of pregnant women treated with Lewemir® FlexPen® and isophane-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 in quantitative terms (61 (40%) vs 49 (31%)), in infants during the intrauterine growth period and after birth (36 (24%)) versus 32 (20%)) was higher in the Levemir® FlexPen® treatment group compared to the isofan-insulin therapy group.

The number of live-born children from mothers who became pregnant afteras were randomized to therapeutic groups for treatment with one of the drugs studied, was 50 (83%) in the 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® 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® FlexPen® treatment group and 3 (2%) in the isofan-insulin.

Children and teens

The efficacy and safety of the Levemir® FlexPen® in children has been studied in two 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 in the age group of two to five years. The results of these studies demonstrated that glycemic control (HbA₁_c) against the backdrop of 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 concentrations measured by patients alone) and absence of weight gain (standard deviation for body weight adjusted according to the sex and age of the patient) against the background of Levemir® FlexPen® treatment, compared with isophane-insulin.

One of the clinical trials was extended for a further 12 months (a total of 24 months of clinical data were obtained) in order to obtain a more complete database for evaluating the formation of antibodies in patients with long-term treatment with Levemir® FlexPen®.

The results obtained in the course of the study indicate that during the first year of treatment against the background of the Levemir® FlexPen® preparation, the titer of antibodies to insulin detemir increased; However, by the end of the second year of treatment, the antibody titer to Lewemir® FlexPen® was reduced in patients to a value slightly above the baseline at the time of initiation of Levemir® FlexPen®. Thus, it is proved,that the formation of antibodies in patients with diabetes mellitus against the background of treatment with Levemir® FlexPen® does not adversely affect the glycemic control and the dose of insulin detemir.

Pharmacokinetics:

Absorption

The maximum concentration in the blood plasma is reached in 6-8 hours after administration.

With a twice daily mode of administration, the equilibrium concentrations of the drug in the blood plasma are achieved after 2-3 injections.

Inside, the individual suction variability is lower in the Levemir® FlexPen® compared to other basal insulin preparations. There were no clinically significant gender differences in the pharmacokinetics of the Levemir® FlexPen® preparation.

Distribution

The average volume of distribution of the Levemir® FlexPene® preparation (approximately 0.1 l / kg) indicates that most of the insulin detemir circulates in the blood.

Metabolism

Inactivation of the Levemir® FlexPene® is similar to that of human insulin preparations; all formed metabolites are inactive. Results of studies of protein binding in vitro and in vivo show the absence of clinically significant interactions between insulin detemir and fatty acids or other drugs that bind to proteins.

Excretion

The terminal half-life after subcutaneous injection is determined by the degree of absorption from the subcutaneous tissue and is 5-7 hours, depending on the dose.

Linearity

With subcutaneous administration, plasma concentrations were proportional to the dose administered (maximum concentration, degree of absorption).

There was no pharmacokinetic or pharmacodynamic interaction between liraglutide and Lewemir® FlexPen® in an equilibrium state, while patients with type 2 diabetes, Lewemir® FlexPen®, were given a single dose of 0.5 U / kg and 1.8 mg liraglutide.

Special patient groups

Pharmacokinetic properties of the 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 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

Research in vitro, in the human cell line, including studies on binding to insulin receptors and IGF-1 (insulin-like growth factor), showed 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 pharmacological safety studies, repeat dose toxicity, 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.

It is not recommended to use Levemir® FlexPen® in children under 2 years of age. clinical studies in children younger than 2 years have not been conducted.

Pregnancy and lactation:

Pregnancy

When using 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,in which the efficacy and safety of combined Levemir® FlexPen® therapy with insulin aspart (152 pregnant women) were studied and compared with isophane-insulin therapy in combination with insulin aspart (158 pregnancies), there was no difference in the overall safety profile during pregnancy, in the outcomes of pregnancy or the health of the fetus and newborn (see section "Pharmacological properties").

Additional data on the efficacy and safety of 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 reproductive system (see section "Pharmacological properties").

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.

Breastfeeding period

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

Women in the period of breastfeeding may need to adjust the dose of insulin and diet.

Dosing and Administration:

The dose of Levemir® FlexPen® should be selected individually in each specific case, based on needs of the patient.

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

Mean plasma glucose values measured alone before breakfast	Correction of the dose of Levemir® FlexPen®, ED
> 10.0 mmol / l (180 mg / dl)	+8
9.1-10.0 mmol / L (163-180 mg / dl)	+6
8.1-9.0 mmol / L (145-162 mg / dL)	+4
7.1-8.0 mmol / L (127-144 mg / dl)	+2
6.1-7.0 mmol / L (109-126 mg / dl)	+2
4.1-6.0 mmol / l	No change (target value)
If any single value of plasma glucose:
3.1-4.0 mmol / L (56-72 mg / dL)	-2
<3.1 mmol / L (<56 mg / dL)	-4

If the drugLevemir® FlexPen® is used as part of the basic-bolus regimen, it should be prescribed 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 with increasing physical activity of the patient, changing his usual diet or with concomitant disease.

The Levemir® FlexPen® medicinal preparation can be used both as a 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 drugs or in addition to liraglutide, Lewemir® FlexPlex® is recommended once a day, starting at a dose of 10 U or 0.1-0.2 U / kg.

The Levemir® FlexPen® drug 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. Lewemir® FlexPen® is for subcutaneous administration only. Levemir® FlexPen® should not be administered intravenously, this can lead to severe hypoglycemia. Also, intramuscular injection should be avoided. Lewemir® FlexPen® is not suitable for use in insulin pumps.

Levemir® FlexPen® is injected subcutaneously into the thigh, anterior abdominal wall, shoulder area, deltoid or gluteal region. Injection sites should be changed regularly 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, in elderly patients and patients with renal or hepatic impairment should more closely monitor the concentration of glucose in the blood and adjust the dose of insulin Detemir individually.

Children and teens

The efficacy and safety of Levemir® FlexPen® in adolescents and children over 2 years of age is confirmed in clinical trials lasting up to 12 months.

Translation from other insulin preparations

Transfer from medications of insulin of average duration of action and from prolonged insulin preparations to the Levemir® FlexPen® preparation may require correction of the dose and time 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 the concomitant hypoglycemic therapy (dose and time of administration of short-acting insulin preparations or a dose of oral hypoglycemic drugs).

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 the section below.

From clinical studies, it is known 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, bruises, 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 continuing treatment 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 the control of carbohydrate metabolism can lead to a temporary deterioration in the state of diabetic retinopathy,at the same time, 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 / 1,000 to <1/100); rarely (≥1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000) and unknown (impossible to estimate based on available data).

Immune system disorders	Infrequently - allergic reaction, potentially allergic reactions, urticaria, skin rash, rashes on the skin *
Immune system disorders	Rarely - Anaphylactic reactions *
Disorders from the metabolism and nutrition	Often - hypoglycemia
Disturbances from the nervous system	Rarely - peripheral neuropathy ("acute pain neuropathy")
Disturbances on the part of the organ of sight	Infrequently refractive disorders
Disturbances on the part of the organ of sight	Infrequently - diabetic retinopathy
Disturbances from the skin and subcutaneous tissues	Infrequently - lipodystrophy *
General disorders and	Often - reactions in places of administration
violations at the site of administration	Infrequently swellings

* See "Description of Selected Adverse Reactions"

Description of individual adverse reactions

Allergic reactions, potentially allergic reactions, hives, skin rashes, skin rashes

When levemir® was used in the basal-bolus regimen, infrequent development of allergic reactions, potentially allergic reactions, hives, skin rashes and skin rashes was noted. However, data from three clinical studies showed frequent development of adverse reactions with Levemir® as part of a 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, lowering blood pressure) are very rare, but are potentially life threatening.

Hypoglycaemia

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, as a rule, develop suddenly. They include the cold yogi, the pallor of the 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 lipohydrophy, lipoatrophy) can develop at the injection site. Adherence to the rule of changing the injection site within one area can help reduce the risk of developing this adverse reaction.

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: slight hypoglycemia, the patient can eliminate himself by taking glucose, sugar or carbohydrate-rich foods inside. 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 administered intramuscularly or subcutaneously (can be administered by a trained person) or an intravenous solution of dextrose (glucose) (can be administered only by a medical professional). It is also necessary to inject dextrose intravenously in the case if the patient does not regain consciousness 10 to 15 minutes after the administration of glucagon. After restoration of consciousness, the patient is recommended to take food rich in carbohydrates, to prevent the recurrence of hypoglycemia.

Interaction:

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

Hypoglycemic action of insulin enhances oral hypoglycemic agents, monoamine oxidase inhibitors, angiotensin-converting enzyme inhibitors, carbonic anhydrase inhibitors, nonselective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, salicylates.

Hypoglycemic action of insulin weakens oral contraceptives, glucocorticosteroids, iodine-containing thyroid hormones, somatropin, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, blockers of "slow" calcium channels, diazoxide, morphine, phenytoin, nicotine.

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

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

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

Incompatibility

Some drugs, for example, containing thiol or sulphite groups, when added to Leveem® FlexPen®, can cause destruction of insulin detemir. Lewemir® FlexPen® should not be added to infusion solutions. This drug should not be mixed with other medicines.

Special instructions:

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

Unlike other insulin preparations, the basis-bolus therapy with the Levemir® FlexPen® does not lead to an increase in body weight.

Levemir® FlexPen® medication provides a smaller increase in body weight, compared with the use of isophane-insulin and insulin glargine.

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

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

Lewemir® FlexPen® provides better glycemic control (based on measuring fasting plasma glucose concentration) compared with the use of 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 must 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.

Hypoglycaemia can develop if the dose of insulin is too high in relation to the need for insulin, with a missed meal or an unplanned intensive exercise.

After compensating for carbohydrate metabolism, for example, with intensified insulin therapy, the symptoms typical for them, precursors of hypoglycemia, can 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 a patient from other insulin preparations

The transfer of a patient to a new type or preparation of another manufacturer's insulin should be carried out under strict medical supervision. If the concentration, producer, type, species (human, analogue of human insulin) and / or method of production thereof changes, dose adjustment may be required. Patients switching to treatment with Levemir® FlexPen® 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.

The simultaneous use of drugs of the thiazolidinedione group and insulin preparations

Cases of chronic heart failure in the treatment of patients with thiazolidinediones in combination with insulin preparations have been reported, especially if such patients have risk factors for developing chronic heart failure. This fact should be taken into account when appointing patients combination therapy with thiazolidinediones and insulin preparations. In the appointment of such combination therapy, it is necessary to conduct medical examinations of patients to identify signs and symptoms of chronic heart failure, increase in body weight and the presence of edema.If the symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

Instructions for patients on the use of the drug

- Do not use Levemir® FlexPlex®.

- In case of allergies (hypersensitivity) to insulin detemir or any of the components of the drug.

- If you have hypoglycemia (low blood sugar).

- In insulin pumps.

- If FlexPen® is dropped, if it is damaged or crushed.

- If the storage conditions of the preparation have been violated, or it has been frozen.

- If insulin has ceased to be transparent and colorless

Before use, Lewemir® FlexPen®:

Check the label to make sure you are using the right type of insulin.

Always use a new needle for each injection to prevent infection.

Lewemir® FlexPlex® and needles are for personal use only.

Method of administration

Lewemir® FlexPen® is for subcutaneous administration only.

Never administer it intravenously or intramuscularly. Each time, change the injection site within the anatomical area. This will help reduce the risk of seals and ulcers at the injection site.It is best to inject the drug into the front of the thigh, the anterior abdominal wall, and the shoulder. Regularly measure blood glucose.

How to handle Lewemir® FlexPen®

Carefully read and follow the enclosed instruction for the patients on the application of Levemir® FlexPen®.

Instruction for patients on the use of Levemir® FlexPen®

Read this manual carefully before use. Lewemir® FlexPene®

Lewemir® FlexPlex® is a unique insulin pen with a dispenser and color coding. The injected dose of insulin, ranging from 1 to 60 units, can vary in steps of 1 unit. Lewemir® FlexPlex® is designed for use with NovoFine® and NovoTvist® disposable needles up to 8 mm long. As a precaution, always carry a spare insulin delivery system in case you lose or damage your Levemir® FlexPan®.

Lewemir® FlexPen®

See Fig. 1

Preparing Lewemir® FlexPen®

Check the label to make sure that your FlexPen® contains the type of insulin you need.

Remove the cap from the syringe pen.

AT.

Remove the protective label with a disposable needles.

Carefully and tightly screw the needle onto the Levemir® FlexPlex®.

FROM.

Remove the outer cap from the needle, but do not throw it away.

Remove and discard the inner needle cap.

- For each injection, use a new needle to prevent infection.

- Be careful not to bend or damage the needle before use.

- To avoid accidental injections, never put the inner cap back on the needle.

Insulin intake check

Even with the correct use of the syringe pen, a small amount of air can accumulate in the cartridge before each injection.

To prevent the ingress of air bubbles and ensure the introduction of the correct dose of the drug:

Type 2 units of the drug by turning the dose selector.

While holding the Lewemir® FlexPlex® with the needle up, tap the cartridge lightly with your fingertip several times to allow air bubbles to move to the top of the cartridge.

Hold the needle with the needle up, press the start button all the way. The dosage selector will return to zero.

At the end of the needle should appear a drop of insulin. If this does not happen, replace the needle and repeat the procedure, but no more than 6 times.

If insulin does not come from the needle, this indicates that the pen syringe is faulty and is not subject to further use.

Dose setting

Make sure that the dose selector is set to "0".

Dial the number of units needed for the injection.

The dose can be adjusted by rotating the dose selector in any direction until the correct dose is established opposite the dosing indicator. When rotating the dose selector, be careful not to accidentally press the start button to avoid dosing the insulin dose.

It is not possible to set a dose that exceeds the number of units remaining in the cartridge.

- You can not use a residue scale to measure the dose of insulin.

Introduction of insulin

Insert the needle under the skin. Use the injection technique recommended by your doctor.

To do the injection, press the start button all the way until "0" appears opposite the dosing indicator.

Be careful: when you inject the drug, you should only press the start button.

When the selector is rotated, the dose will not enter the dose.

When removing the needle from under the skin, hold the start button all the way down.

After injection, leave the needle under the skin for at least 6 seconds. This will ensure the introduction of a full dose of insulin.

TO.

Point the needle into the outer cap of the needle without touching the cap. When the needle goes inside, put on the cap and unscrew the needle (see Figure A-K).

Throw out the needle, observing the precautionary measures, and close the syringe handle with a cap.

- Remove the needle after each injection and never store Levemir® FlexPen® with attached needle. Otherwise, levemir® FlexPix® may leak out, which may result in an incorrect dosage.

- Persons caring for the patient should be careful when removing and discarding needles to avoid risk of accidental needle pricking.

- Throw out the used Leveem® FlexPen® with the needle disconnected.

- Needles and Levemir® FlexPix® are for personal use only.

Storage and Care

Lewemir® FlexPlex® is designed for effective and safe use and requires careful handling. In the event of a fall or strong mechanical impact, it is possible to damage the syringe handle and leakage of insulin. The Lewemir® FlexPen® surface can be cleaned with a cotton swab dipped in alcohol.Do not immerse the syringe handle in alcohol, do not wash or lubricate it. this may damage the mechanism.

Do not refill Leewemir® FlexPen®.

Effect on the ability to drive transp. cf. and fur:

The ability of patients to concentrate and react quickly may be compromised by hypoglycemia, which can be dangerous in situations where these abilities are particularly necessary (for example, when driving vehicles or working with machinery 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, the desirability of driving a vehicle or performing such work should be considered.

Form release / dosage:

Solution for subcutaneous administration, 100 units / ml.

Packaging:

3 ml per cartridge of glass 1 of hydrolytic class, sealed with a disk of brombutyl rubber on one side and sealed in a plastic multi-dose disposable syringe pen for multiple injections on the other.

For 5 plastic multi-dose disposable syringes-pens for multiple injections together with instruction but application in a cardboard pack.

Storage conditions:

Store at a temperature of 2 to 8 ° C (in the refrigerator), but not next to the freezer. Do not freeze. To protect from light, store FlexPen® with the cap on.

Lewemir® FlexPen® should be protected from the effects of excessive heat and light.

Used or carried as a spare syringe pen with the drug do not store in the refrigerator. Store for 6 weeks at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Shelf life:

30 months.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000596

Date of registration:11.01.2010

The owner of the registration certificate:Novo Nordisk A / SNovo Nordisk A / S Denmark

Manufacturer: & nbsp

NOVO NORDISK, A / S Denmark

Representation: & nbspNOVO NORDISK TOVNOVO NORDISK TOVDenmark

Information update date: & nbsp25.10.2015