Levemir® Penfield® (Levemir® Penfill®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceInsulin DetemirInsulin Detemir
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  • 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 100 ED (14.2 mg);

    Excipients: glycerol 16 mg, phenol 1.8 mg, metacresol 2.06 mg, zinc 65.4 μg (as zinc acetate), sodium hydrogen phosphate dihydrate 0.80 mg, sodium chloride 1.17 mg, acid hydrochloric q.s. or sodium hydroxide q.s., water for injection up to 1 ml.

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

    1 unit of insulin detemir contains 0.142 mg of salt-free insulin detemir.

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

    Pharmacotherapeutic group:hypoglycemic agent - long-acting insulin analog
    ATX: & nbsp

    A.10.A.E.05   Insulin Detemir

    Pharmacodynamics:

    The Levemir® Penfill® preparation 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® Penfill® action is significantly less variable than isophane-insulin and insulin glargine.

    The prolonged action of the drug Levemir® Penphill® is due to the pronounced self-association of insulin detemir molecules at the site of injection and the binding of the drug molecules to albumin by binding 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® Penphyl® 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 fasting plasma glucose concentration day after day in the treatment of patients with the Levemir® Penphyl® preparation, 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) on the background of therapy with the drug Levemir® Penfill®, was comparable to that for the treatment of isophane-insulin and insulin 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 combined use of Levemir® Penfill® and oral hypoglycemic medications resulted in a 61-65% reduction in the risk of mild hypoglycemia at night, in contrast to isophane-insulin.

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

    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 HbA1c <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 therapy with liraglutide with metformin, were prescribed Levemir® Penfill® 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® Penphill®, demonstrated a further decrease in the HbA1FROM 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® Penfill® to liraglutide therapy, the latter retained its advantage with respect to a statistically significant decrease in body weight in patients, see Table 2.

    Table 2. Clinical trial data - therapy with Levemir®, prescribed in addition to the combined scheme of treatment with liraglutide with metformin

    Weeks

    treatment

    Patients,

    randomized

    for of obtaining

    of therapy drug

    Levemir®

    Penfill® in

    addition to therapy of liraglootid+metformin

    N = 160

    Patients,

    randomized

    for getting

    of therapy

    lyraglutype +

    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

    HbA1C <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)

    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 Levemir® Penphill® compared to isophane-insulin,appointed in the basis / bolus therapy. Glycemic control (HbA1c) on background therapy with Levemir® Penfill® it was comparable to that in the treatment of isophane insulin, but with a lower risk of nocturnal hypoglycaemia and lack of weight gain during treatment with the drug Levemir® Penfill®.

    Results from clinical studies evaluating the basal-bolus insulin therapy, suggest a comparable incidence of hypoglycaemia as a whole against the background of therapy with Levemir® Penfill® and isophane insulin. Analysis of the development of nocturnal hypoglycemia in patients with type 1 diabetes showed a significantly lower incidence of lung nocturnal hypoglycemia during treatment with the drug Levemir® Penfill® (when the patient may self-eliminate state hypoglycemia, hypoglycemia, and when the result is confirmed by measurement of capillary blood glucose concentration of less than 2 8 mmol / l or effect of the concentration measuring plasma glucose less than 3.1 mmol / l), compared with that in the application of isophane insulin; wherein between the two study medication did not reveal differences in the occurrence frequency of episodes of nocturnal hypoglycemia lung in patients with type 2 diabetes.

    The profile of nocturnal glycemia is more flat and even in Levemir® Penfill® compared to isofan-insulin, which is reflected in a lower risk of developing nocturnal hypoglycemia.

    With the use of Levemir® Penfill®, 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® Penphill® 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® Penphill®, a similar decrease was observed in comparison with the group receiving isophane-insulin HbA1c at 36 weeks of gestation. A group of patients treated with Levemir® Penphill® and a group receiving isofan-insulin therapy showed similarity throughout the gestation period for the overall profile of HbA1C.

    Target level HbA1c <6.0% at 24 and 36 weeks of gestation was achieved in 41% of patients in the levemir® Penphill® treatment group and 32% 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 took Levemir® Penphill®, compared to the group receiving isophane-insulin therapy.

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

    Both groups of pregnant women treated with Levemir® Penphill® 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%) vs. 32 (20%)) was higher in the Levemir® Penphill® 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® Penphyl® treatment group and 55 (89%) in the isophane treatment group -insulin. The number of children born with congenital malformations was 4 (5%) in the treatment group Levemir® Penphill® and 11 (7%) in the isofan-insulin treatment group. Of these, serious congenital malformations were noted in 3 (4%) children in the Levemir® Penphill® treatment group and 3 (2%) in the isophane-insulin treatment group.

    Children and teens

    The efficacy and safety of Levemir® Penphill® 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 who have type 1 diabetes (a total of 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 (HbA1c) on the background of therapy with the drug Levemir® Penfill® was comparable to that in the treatment of isophane-insulin, with their appointment in basal-bolus therapy. In addition, there was a lower risk of developing nocturnal hypoglycemia (based on plasma glucose concentrations measured by patients on their own) and the absence of weight gain (standard deviation for body weight adjusted according to the sex and age of the patient) when treated with Levemir® Penfill®, in comparison 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® Penphill®.

    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® Penphill®; However, by the end of the second year of treatment, the antibody titer to Lewemir® Penfill® was reduced in patients to a value slightly above the baseline at the time of initiation of Levemir® Penfill®.Thus, it is proved that the formation of antibodies in patients with diabetes mellitus against the background of treatment with Leveum® Penphill® 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® Penfill® than in other basal insulin preparations. Clinically significant intervertebral differences in the pharmacokinetics of the Levemir® Penphill® preparation were not identified.

    Distribution

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

    Metabolism

    Inactivation of the Levemir® Penfill® preparation 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 were no pharmacokinetic or pharmacodynamic interaction between the drug and liraglutide Levemir® Penfill®, in equilibrium, while the introduction of patients with type 2 diabetes drug Levemir® Penfill® in a single dose of 0.5 U / kg and 1.8 mg liraglutide.

    Special patient groups

    The pharmacokinetic properties of the drug Levemir® Penfill® were investigated in children (6-12 years) and adolescents (13-17 years) and compared with the pharmacokinetic properties in adults with type 1 diabetes. No differences were found. Clinically significant differences in pharmacokinetics Levemir® Penfill® between older and younger patients or between patients with impaired renal and hepatic function and healthy patients, have 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 studies 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.

    It is not recommended to use Levemir® Penphill® 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 Leveum Penfill® 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® Penfill® therapy with insulin aspart (152 pregnancies) 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® Penfill®, 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 the 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® Penfill® 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 titration of doses:

    Mean plasma glucose values ​​measured alone before breakfast

    Correction of the dose of Levemir® Penfill®, YE

    > 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 Levemir® Penphill® 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 with increasing physical activity of the patient, changing his usual diet or with concomitant disease.

    Medicinal preparation Leveem® Penfill® 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 that Levemir® Penphyl ® be used once a day, starting at a dose of 10 U or 0.1-0.2 U / kg. The medicinal preparation Levemir® Penphill® 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 followed.

    Levemir® Penfill® is intended for subcutaneous administration only. Levemir® Penfill® should not be administered intravenously, because this can lead to severe hypoglycemia. Also, intramuscular injection should be avoided. Levemir® Penfill® is not suitable for use in insulin pumps. Levemir® Penfill® is injected subcutaneously into the thigh, anterior abdominal wall, shoulder region, 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.

    Translation from other insulin preparations

    Transfer from medications of insulin of average duration of action and from prolonged insulin preparations to the drug Levemir® Penfill® may require dose adjustment 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).

    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

    Efficacy and safety of Levemir® Penfill® in adolescents and children older than 2 years confirmed in clinical studies lasting up to 12 months.

    Side effects:

    Adverse reactions observed in patients using the Levemir® Penphyl® preparation are mainly dose-dependent and develop due to the pharmacological effect of insulin. Hypoglycemia, as a rule, is the most common side effect. Hypoglycemia develops if too high a dose of the drug is administered relative to the body's need for insulin. From clinical studies, it is known, yoke severe hypoglycemia, requiring the intervention of third parties, develop approximately 6% patients receiving Levemir® Penphill®.

    Reactions at the site of administration may occur more frequently with Levemir® Penfill® than with human insulin. These reactions include redness, inflammation, bruising, swelling and itching at the injection site. Most of the reactions at the sites of administration are insignificant and temporary. disappear when continuing treatment for several days to several weeks.

    The proportion of patients receiving treatment and who are expected to develop side effects is estimated at 12%. The incidence of side effects, which, according to the general assessment, is related to the Levemir® Penphill® preparation, during clinical trials, is presented below.

    Metabolic and nutritional disorders

    Frequent (> 1/100, <1/10)

    Hypoglycemia:

    Symptoms of hypoglycemia usually develop suddenly. They include cold sweats, pallor of the skin, fatigue, nervousness or tremor, anxiety, unusual fatigue or weakness, disorientation, decreased concentration, drowsiness, severe hunger, visual impairment, headache, nausea, palpitations.Severe hypoglycemia can lead to loss of consciousness and / or convulsions, temporary or irreversible impairment of brain function up to a lethal outcome.

    General disorders and reactions at the injection site

    Frequent (> 1/100, <1/10)

    Reactions at the site of administration:

    Local hypersensitivity reactions (redness, swelling, and itching at the injection site) may develop during insulin treatment. These reactions are usually temporary and disappear when the treatment is continued.

    Rare (> 1/1000, <1/100)

    Lipodystrophy:

    Lipodystrophy can develop at the injection site as a result of non-compliance with the rule of changing the injection site within one area.

    Edema:

    Edema can occur at the initial stage of insulin therapy. These symptoms are usually temporary.

    Immune system disorders

    Rare (> 1/1000, <1/100)

    Allergic reactions, urticaria, skin rash:

    Such symptoms can develop due to generalized hypersensitivity. Other signs of generalized hypersensitivity may include itching, sweating, gastrointestinal disorders, angioedema, difficulty breathing, palpitations, and lowering blood pressure.Generalized hypersensitivity reactions (anaphylactic reactions) are potentially life threatening.

    Impaired Visual Function

    Rare (> 1/1000, <1/100)

    Refractive disorders:

    Refractive disorders can occur at the initial stage of insulin therapy. These symptoms are usually temporary.

    Diabetic retinopathy:

    Long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy. However, the 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.

    Nervous System Disorders

    Very rare (> 1/10000, <1/1000)

    Peripheral Neuropathy:

    Rapid improvement in glycemic control can lead to a state of "acute pain neuropathy," which is usually reversible.

    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 constantly 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 reinforce 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, preparations containing ethanol.

    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.

    Under the influence of reserpine and salicylates, both weakening and enhancement of the action of the drug are possible.

    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 enhance and prolong the hypoglycemic effect of insulin.

    Incompatibility

    Some drugs, for example, containing thiol or sulphite groups, when added to the Levemir® Penfill® preparation, can cause the destruction of insulin detemir.

    Levemir® Penfill® should not be added to infusion solutions.

    Special instructions:

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

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

    Levemir® Penfill® treatment 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 lesser 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® Penphill® in combination with oral hypoglycemic drugs.

    Levemir® Penfill® 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 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® Penfill® 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 Levemir® Penphill®

    Leveem® Penfill® cartridges are designed for use with Novo Nordisk insulin injection systems and NovoFine needles. If both Levemir® Penfill® and another insulin in the Penfill® cartridge are used simultaneously for treatment, two Novo Nordisk insulin injection systems should be used, one for each type of insulin.

    Levemir® Penfill® is intended for individual use only. Do not refill the cartridge with insulin.

    Before using Levemir® Penfill®:

    - Check the labeling on the label and make sure that you use the type of insulin you need.

    - Always check the cartridge, including the rubber piston. Do not use the cartridge if it has been damaged or if the width of the visible part of the rubber piston is greater than the width of the white code strip. Return the cartridge to the supplier.

    - Disinfect the rubber membrane with a cotton swab dipped in medical alcohol.

    - Always use a new needle for each injection to avoid contamination.

    Do not use Levemir® Penfill®:

    - In insulin pumps.

    - If the cartridge or insertion device containing the cartridge is dropped, or if the cartridge is damaged or crushed, as there is a risk of leakage of insulin.

    - If the storage conditions of the drug do not match the specified, or if the drug has been frozen.

    - If insulin has ceased to be transparent and colorless.

    How to administer this insulin

    - Insulin should be injected under the skin. Use the injection technique recommended by your doctor, or follow the insulin administration instructions in the manual for the insulin delivery device.

    - Hold the needle under the skin for at least 6 seconds to be sure that you have entered the full dose of the drug.

    - Always remove and discard the needle after each injection. Otherwise, it is possible to leak the liquid from the cartridge, which can lead to an incorrect dosage of insulin.

    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 in cartridges of glass 1 of hydrolytic class, sealed with discs of brombutyl rubber on one side and pistons of bromobutyl rubber on the other.

    5 cartridges per blister of PVC / aluminum foil.

    1 blister with instructions for use in a cardboard box.

    Storage conditions:

    Store at a temperature of 2 to 8 ° C (in the refrigerator), but not next to the freezer. Do not freeze.

    Store in a cardboard box to protect from light.

    For opened cartridges: 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-000597
    Date of registration:18.01.2010
    The owner of the registration certificate:Novo Nordisk A / SNovo Nordisk A / S Denmark
    Manufacturer: & nbsp
    Representation: & nbspNOVO NORDISK TOVNOVO NORDISK TOVDenmark
    Information update date: & nbsp25.10.2015
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