Expiration date: 09/2026

Release form and composition:

The solution for the p/to the introduction transparent, colorless.

1 ml 1 syringe pen contains:

insulin detemir 100 UNITS* 300 UNITS*

Auxiliary substances: mannitol, phenol, metacresol, zinc acetate, sodium chloride, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, water d/I.

* 1 UNIT contains 142 g of salt-free insulin detemir, which corresponds to 1 unit of human insulin (IU).

3 ml - pen with multidose dispenser (5) - packs of cardboard.

Pharmacological action:

Hypoglycemic drug. It is a soluble analog of human basal long-acting insulin with a flat and predictable profile of activity. Is produced by biotechnology recombinant DNA using a strain of Saccharmyces cerevisiae.

The action profile of Levemir® Flexpen® is much less variable compared with isophane insulin and insulin glargine.

The prolonged action of Levemir® Flexpen® due to the pronounced self-Association of insulin detemir molecules at the injection site, and binding molecules of the drug to albumin through a connection to a side chain. Insulin detemir compared with isophane insulin to peripheral tissues-targets goes slowly. These combined mechanisms of delayed distribution gives a more reproducible profile of the adsorption and action of the drug Levemir® Flexpen® compared to isophane insulin.

Interacts with the specific receptor zitoplazmaticescoy external cell membrane of cells to form insulin-receptor complex stimulates intracellular processes, including synthesis of several key enzymes (geksokinazoj, pyruvate kinase, glikogensintetaza).

The decrease in the content glucose in the blood due to its increase of intracellular transport, increased assimilation of tissues, stimulation of lipogenesis, glikogenogeneza, a decrease in the rate of glucose production by the liver.

For doses of 0.2-0.4 U/kg 50% of maximum effect of the drug is in the range of 3-4 h to 14 h after administration. Duration of action is up to 24 hours depending on the dose, which enables the introduction of 1 times/day or 2 times/day.

After p/to the introduction of the pharmacodynamic response was observed, proportional to the administered dose (maximum effect, duration of action, total effect).

Long-term studies (ge6 months) an indicator of the level of glucose in blood plasma fasting in patients with diabetes mellitus type 1 was better compared to isophane insulin, appointed in basis/bolus therapy. Glycemic control (glycated hemoglobin - HbA1C) during therapy with Levemir® Flexpen® was comparable in the treatment of isophane insulin, with lower risk of nocturnal hypoglycaemia and no increase in body mass on the background of the use of the drug Levemir® Flexpen®.

Profile night glucose control is more flat and smooth in the drug Levemir® Flexpen® compared to isophane insulin, which is reflected in a lower risk of developing hypoglycemia at night.

Pharmacokinetics:

Suction

When s/to the introduction of the concentration in serum was proportional to the administered dose.

Cmax achieved through 6-8 h after injection. The daily mode of introduction of Css is attained after 2-3 doses.

Interindividual variability in absorption is lower in the Levemir® Flexpen® compared to other drugs basal insulin.

Distribution

The average Vd of insulin detemir (approximately 0.1 l/kg) indicates that a high fraction of insulin detemir is circulating in the blood.

Metabolism

Biotransformation of insulin detemir was similar with that of human insulin preparations, all metabolites formed are inactive.

Excretion

Terminal T1/2 after p/to the injections depends on the extent of absorption from subcutaneous tissues and is 5-7 hours depending on the dose.

Pharmacokinetics in special clinical cases

No clinically significant gender differences in pharmacokinetics of Levemir® Flexpen® have been identified.

The pharmacokinetic properties of Levemir® Flexpen® were investigated in children (6-12 years) and adolescents (13-17 years) and compared. Differences in pharmacokinetic properties as compared with adult patients with diabetes mellitus type 1 not found.

Clinically significant differences in pharmacokinetics of Levemir® Flexpen® between the elderly and younger patients, or between patients with impaired renal function and liver and healthy patients, were not revealed.

Indications:

• diabetes.
  

Dosing regimen:

Levemir® Flexpen® designed for p/to the introduction.

The dose is determined individually. The Levemir® Flexpen® should be used 1 or 2 times/day based on the needs of the patient. Patients requiring the use of the drug 2 times/day for optimal control of blood glucose levels, can introduce a bedtime dose either at dinner time or before bedtime, or 12 hours after the morning dose.

Levemir® Flexpen® is injected in the femoral region, anterior abdominal wall or shoulder. It is necessary to change the injection site within the anatomical region to prevent the development of lipodystrophy.

In elderly patients and in patients with renal or hepatic insufficiency should more carefully monitor the level of blood glucose and correction doses of the drug.

Dose adjustment may also be required with increased physical activity of the patient, changing his usual diet or during concomitant illness.

When transferring from insulin average duration of action and long-acting insulin to insulin Levemir® Flexpen® may require adjustment of dose and timing of administration. It is recommended to carefully monitor the level of blood glucose during transfer and in the first weeks of a new drug. May require correction of concomitant hypoglycemic therapy (dose and time of administration of short-or insulin dose of oral hypoglycemic drugs).

Rules for the use of the drug Levemir® Flexpen®

Levemir® Flexpen® pen dispenser. The administered dose of insulin ranges from 1 to 60 units can be changed in increments of 1 unit. Needle novofayn®S to 8 mm or shorter in length designed for use with Levemir® Flexpen®. Marking's are needles with short tip. To comply with the precautions you should always carry a spare device for administering insulin in case of loss or damage Flexpen®.

Before you use Levemir® Flexpen® you should make sure that you select the correct type of insulin.

Preparations for the injection: it should remove the cap to disinfect the rubber membrane with swab dipped in rubbing alcohol to remove the protective label from the needle with a short cap Novofine®S gently screw the needle on the Levemir® Flexpen® to remove outer and inner caps from the needle (do not throw the outer cap). For each injection you should always use a new needle.

Preliminary removal of air from the cartridge. During normal use of the pen before each injection needle and the reservoir can accumulate air. To avoid getting air bubbles and to enter the prescribed dose of the drug should comply with the following guidelines:

• to collect 2 UNITS of the drug
  
• place the Levemir® Flexpen® vertically upwards and the needle a few times, gently tap the reservoir with your finger tip so that the air bubbles moved to the top of the cartridge
  
• hold the Levemir® Flexpen® with the needle upwards, press the start button until the dose selector returns to zero
  
• at the end of the needle should see a drop of insulin if it does not, then repeat the procedure, but not more than 6 times. If insulin is not supplied from the needle, which indicates that the pen is faulty and is not subject to further use.
  

Setting the dose. Make sure that the dose selector is set to 0. Dial the number of UNITS required for injection. The dose can be adjusted by rotating the dosage selector in either direction. When turning the dose selector counter-clockwise, be careful not to accidentally press the trigger to prevent release of insulin dose. To set a dose exceeding the number of UNITS remaining in the cartridge, it is impossible.

The introduction of the drug. Insert the needle subcutaneously. To make the injection, press the start button until it stops. With the introduction of the drug should only press the start button. After injection, the needle should be left under the skin for 6 seconds. When removing the needle, hold the release button is fully pressed, this will ensure that the introduction of the full dose of the drug.

Removing the needle. To close outer needle cap and Unscrew it from the pen. Discard the needle, observing precautions. After each injection, the needle should be removed. Otherwise, when the temperature of the liquid may leak from the pen.

Medical staff, relatives and others to care for patients should follow the General rules of precautions in removal and disposal of needles to avoid the risk of accidental pricking with a needle.

Used Levemir® Flexpen® should be discarded in detached needle.

Storage and care. The surface of the pen can be cleaned with a cotton swab dipped in rubbing alcohol. Do not immerse the pen in rubbing alcohol to clean and lubricate it as this may damage the device. Avoid damage to the pen dispenser with Levemir® Flexpen®.

Side effects:

Adverse reactions observed in patients using Levemir® Flexpen® are mainly dose-dependent and are caused by the pharmacological effect of insulin. The most frequent side effect is hypoglycaemia, which occurs when the introduction of too high a dose of the drug on the body's need for insulin. From clinical studies it is known that severe hypoglycemia, defined as the need for the intervention of third parties, develop approximately 6% of patients receiving Levemir® Flexpen®.

The proportion of patients receiving treatment with Levemir® Flexpen®, which is expected to develop side effects is estimated as 12%. The incidence of side effects, which are generally assessed are Levemir® Flexpen® during clinical trials, presented below.

Adverse reactions associated with the effect on carbohydrate metabolism: often (gt1%,t10%) - hypoglycemia, symptoms which usually develop suddenly and may include pale skin, cold sweat, fatigue, nervousness, tremor, anxiety, unusual tiredness or weakness, violation of orientation, breach of concentration, sleepiness, feeling of hunger, blurred vision, headache, nausea, palpitations. Severe hypoglycemia can lead to unconsciousness and/or seizures, temporary or permanent impairment of brain function or death.

Local reactions: in 2% of cases - local hypersensitivity reactions (redness, swelling and itching at the site of injection), usually of a temporary nature, i.e. disappear with continued treatment rare (gt0.1%, t1%) - lipodystrophy (as a result of non-compliance with the rules of changing the injection site within one area).

Allergic reactions: rarely (gt0.1%, t1%) - urticaria, skin rash, and generalized reactions - itching, increased sweating, disorders of the gastrointestinal tract, angioedema, shortness of breath, tachycardia, decrease in blood pressure.

On the part of the organ of vision: rare (gt0.1%, t1%), violation of refraction (usually temporary and occurs in the beginning of treatment with insulin), diabetic retinopathy (sustained improvement in glycemic control reduces the risk of progression of diabetic retinopathy, however, intensification of insulin therapy with abrupt improvement in the control of carbohydrate metabolism can lead to a temporary deterioration of diabetic retinopathy).

From the nervous system: very rare (gt0.01%, t0.1%) - peripheral neuropathy, which is usually reversible. Rapid improvement of glycemic control may be associated with development of acute neuropathic pain, which is usually reversible.

Other: rarely (gt0.1%, t1%) - swelling (occur at the initial stages of insulin therapy and are usually temporary).

Contraindications:

• increased individual sensitivity to product components.
  

It is not recommended to use Levemir® Flexpen® in children under 6 years of age, because clinical studies in this group of patients have not been conducted.

Pregnancy and lactation:

Currently, there are no data of the clinical use of insulin detemir during pregnancy and lactation.

When planning pregnancy and during pregnancy is necessary to conduct careful monitoring of patients with diabetes and control the glucose level in the blood plasma. The need for insulin usually decreases in the first trimester and gradually rises in the II and III trimester of pregnancy. Shortly after birth the need for insulin quickly returns to the level it was before pregnancy.

In the period of breast-feeding may be necessary to correct dose and diet.

In experimental studies in animals have not found differences between embryotoxic and teratogenic action of insulin detemir and human insulin.

Special instructions:

Generalized allergic reactions are potentially life-threatening.

Unlike other insulins, intensive therapy with Levemir® Flexpen® does not increase body mass.

Smaller in comparison with other insulins, the risk of nocturnal hypoglycemia allows more intensively to carry out the selection of doses to achieve target blood glucose levels.

Levemir® Flexpen® provides better glycemic control (based on measurements of fasting plasma glucose) compared with insulin isophane. Lack of dose or discontinuation of treatment, especially in diabetes mellitus type 1 can lead to the development of hyperglycemia or diabetic ketoacidosis. Typically, the first symptoms of hyperglycemia are gradually, for a few hours or days. These symptoms include thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, the smell of acetone in exhaled air. In diabetes type 1 if left untreated, hyperglycemia leads to the development of diabetic ketoacidosis and can lead to death.

Hypoglycemia can develop if the insulin dose is too high in relation to the need for insulin.

Skipping a meal or unplanned strenuous physical activity may lead to hypoglycemia.

After the compensation carbohydrate exchange, for example, when intensified insulin therapy, patients can change their typical symptoms-signs of hypoglycemia, what patients need to be informed. The usual symptoms-signs can disappear in the long course of diabetes.

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

A patient on a new type of drug or insulin from another manufacturer should be under strict medical supervision. If you change concentration, manufacturer, type, species (animal, human, analogues of human insulin) and/or the method of its production (genetic engineering or animal insulin) may require dosage adjustment. Patients, going over treatment with Levemir® Flexpen®, may need to change the dose, compared to previously used doses of insulin. The need for dose adjustment may occur after the first dose or during the first few weeks or months.

Levemir® Flexpen® should not be administered in/in, as this may lead to severe hypoglycemia.

If the Levemir® Flexpen® is mixed with other insulin preparations the profile of action of one or both components will change. Mixing Levemir® Flexpen® with fast-acting insulin analog like insulin aspart, results profile actions with reduced and delayed maximum effect compared to their separate administration.

Levemir® Flexpen® is not intended for use in insulin pumps.

Effects on ability to drive vehicles and management mechanisms

The patients ' ability to concentration of attention and speed of reaction can be violated at the time of hypoglycemia and hyperglycemia that may pose a risk in situations where these abilities are especially needed (for example when driving or working with machines and mechanisms). Patients should be advised to take measures to prevent hypoglycemia and hyperglycemia while driving and operating machinery. This is especially important for patients with no or reduced severity of symptoms-the harbingers of developing hypoglycemia or who have frequent episodes of hypoglycemia. In these cases, you should consider the appropriateness of performing such work.

Overdose:

A certain dose is required for insulin overdose is not installed, however, hypoglycaemia may develop gradually, if you enter too high a dose for a particular patient.

Treatment: mild hypoglycemia, the patient can remove the, taking into glucose, sugar or carbohydrate-rich foods. Therefore, patients with diabetes are advised to constantly carry around a sugar, sweets, biscuits or sugary fruit juice.

In the case of severe hypoglycemia when the patient is unconscious, should be administered from 0.5 to 1 mg glucagon/m or s/C (may introduce a trained person), or to/dextrose solution (glucose) (can enter only a medical professional). Also, it is is administered dextrose if after 10-15 min after injection of glucagon, the patient regains consciousness. After recovering consciousness, the patient is advised to take food rich in carbohydrates to prevent recurrence of hypoglycemia.

Drug interactions:

Hypoglycemic effect of insulin increase the oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, nonselective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, drugs containing ethanol.

Hypoglycemic effect of insulin to weaken oral contraceptives, corticosteroids, tireoidnye hormones, tiazidnye dioretiki, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, blockers slow calcium channels, diazoxide, morphine, phenytoin, nicotine.

Under the influence of rezerpina and salicylates may as weakening, and strengthening actions of the drug.

Octreotide, lanreotide can both improve and reduce the body's need for insulin.

Beta-adrenoblokatora may mask symptoms of hypoglycaemia and delay recovery from hypoglycemia.

Ethanol can enhance and prolong the hypoglycemic effect of insulin.

The results of studies of protein binding in all vitr and in viv showed no clinically significant interactions between insulin detemir and fatty acids or other drugs, binds to a protein.

Pharmaceutical interaction

Some medicines, for example, containing a thiol or sulphite, when added to Levemir® Flexpen®, can cause destruction of insulin detemir. Levemir® Flexpen® should not be added to infusion solutions.

Terms and conditions of storage:

List B. the Drug should be stored in a refrigerator at 2° to 8°C (away from the freezer) do not freeze. Shelf life - 2 years.

To protect from light the pen should be stored with a plastic cap.

After the first use of Levemir® Flexpen® should not be stored in the refrigerator. Used or carried as a spare syringe pen with with Levemir® Flexpen® should be stored at temperature not exceeding 30°C for up to 6 weeks.

The drug should be stored out of reach of children.