Active material: Insulin detemir
When ATH: A10AE05
CCF: Human insulin analog long-acting
ICD-10 codes (testimony): E10, E11
When CSF: 15.01.01.04
Manufacturer: NOVO NORDISK A/S (Denmark)
Pharmaceutical form, composition and packaging
The solution for the p / to the introduction clear, colorless.
|1 syringe pen
|100 U *
|300 U *
Excipients: mannitol, phenol, cresol, Zinc acetate, sodium chloride, disodium phosphate dihydrate, Sodium hydroxide, hydrochloric acid, water d / and.
* 1 ED contains 142 g of salt-free insulin detemir, corresponding 1 Power. human insulin (ME).
3 ml – pen with multidose dispenser (5) – packs cardboard.
Hypoglycemic agents. It is a soluble analog of human basal long-acting insulin with a flat and predictable profile of activity. Produced by recombinant DNA biotechnology using the strain Saccharomyces cerevisiae.
Profile of the drug Levemir® FlexPen® variabelen significantly less compared to izofanom insulin and insulin glargine.
The prolonged effect of the drug Levemir® FlexPen® caused severe self-association of insulin detemir molecules at the injection site and the binding of molecules to albumin preparation by coupling of the side chain. Insulin detemir compared with izofanom insulin to peripheral target tissues goes slowly. These combined mechanisms of delayed distribution gives a more reproducible absorption profile of the drug and Levemir® FlexPen® compared to insulin izofanom.
It interacts with a specific receptor cytoplasmic outer cell membrane to form insulin-receptor complex, stimulating intracellular processes, incl. Several key enzymes (geksokinaza, pyruvate, glikogensintetaza).
The decrease in blood glucose due to an increase of intracellular transport, increasing assimilation tissue, stimulation of lipogenesis, glikogenogeneza, reducing the rate of hepatic glucose production.
For doses 0.2-0.4 U / kg 50% the maximum effect of the drug comes in the range of 3-4 h to 14 hours after injection. The duration of action is up to 24 hours depending on the dose, which enables administration 1 time / day or 2 times / day.
After p / to the introduction of pharmacodynamic response was observed, proportional to the administered dose (maximum effect, duration, cumulative effect).
In long-term studies (≥6 months) figure glucose fasting plasma in patients with diabetes mellitus type 1 It was better than insulin izofanom, appointed to the basis / bolus therapy. Glycemic control (glycated hemoglobin – HbA1C) on background therapy with Levemir® FlexPen® It was comparable to that in the treatment of insulin izofanom, with a lower risk of nocturnal hypoglycaemia and lack of weight gain during treatment with the drug Levemir® FlexPen®.
Profile Night glucose control is more flat and smooth at the drug Levemir® FlexPen® compared to insulin izofanom, which is reflected in a lower risk of nocturnal hypoglycemia.
When s / to a serum concentrations were proportional to the administered dose.
Cmax achieved through 6-8 hours after injection. With twice daily regimen introduction of the Css achieved after 2-3 introduced.
Interindividual variability in absorption is lower in the drug Levemir® FlexPen® in comparison with other drugs basal insulin.
Average Vd Insulin detemir (about 0.1 l / kg) indicates, that a high percentage of insulin detemir is circulating in the blood.
Biotransformation insulin detemir similar to that in preparations of human insulin; all metabolites formed are inactive.
Терминальный T1/2 after s / c injection is determined by the degree of absorption from the subcutaneous tissue and is 5-7 hours depending on the dose.
Pharmacokinetics in special clinical situations
No clinically significant gender differences in the pharmacokinetics of the drug Levemir® FlexPen® There were no.
The pharmacokinetic properties of the drug Levemir® FlexPen® They 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.
No clinically significant differences in the pharmacokinetics of the drug Levemir® FlexPen® between elderly and younger patients, or between patients with impaired renal and hepatic function, and healthy patients, not found.
Levemir® FlexPen® for s / c administration.
The dose is determined individually. The drug Levemir® FlexPen® should be appointed 1 or 2 times / day based on the patient's needs. Patients, which requires the use of the drug 2 times / day for optimal control of blood glucose levels, the evening dose can be administered either during dinner, or before going to bed, or via 12 hours after the morning dose.
Levemir® FlexPen® is introduced into the femoral region, the anterior abdominal wall or shoulder. It is necessary to change the injection site within the anatomical region, to prevent the development of lipodystrophy.
In patients Seniors, and y Patients with renal or hepatic insufficiency should more carefully control the level of glucose in the blood and to conduct correction of the dose.
Dose adjustment may also be required in the amplification of the physical activity of the patient, change its usual diet or during concomitant diseases.
At Translated from the intermediate-acting insulin and long-acting insulin to insulin Levemir® FlexPen® you may need correction of dose and timing of administration. It is recommended that careful monitoring of blood glucose levels during the transfer and in the first week of the appointment of a new drug. You may need correction of concomitant hypoglycemic therapy (Dose and time of administration of short insulin or oral hypoglycemic drug dose).
How to use the drug Levemir® FlexPen®
Levemir® FlexPen®– syringe pen with dispenser. The administered dose of insulin ranges from 1 to 60 Units can be changed in steps 1 edïnïcw. Needles NovoFayn®S up to 8 mm or shorter length is designed for use with Levemir® FlexPen®. Marking S have short needle tip. For precautions should always carry a spare insulin delivery device in case of loss or damage FleksPen®.
Before using the drug Levemir® FlexPen® make sure, that the correct type of insulin.
Preparing for injection: should remove the cap; rubber septum sanitized with a swab, dipped in rubbing alcohol; remove the protective label from the needle with a short cap NovoFayn®S; carefully screw the needle in Levemir® FlexPen®; remove the outer and inner caps from the needle (do not throw away the outer cap). Each injection should always use a new needle.
Preliminary air evacuation from the cartridge. In normal use, the pen before each injection needle and a reservoir can accumulate air. To avoid getting air bubbles and enter the assigned dose follow these guidelines:
-dial 2 ED drug;
-arrange Levemir® FlexPen® vertically upwards and the needle a few times gently tap the reservoir tip of your finger, air bubbles moved to the top of the cartridge;
-holding Levemir® FlexPen® needle up, press the start button all the way; dose selector returns to zero;
-at the end of the needle should see a drop of insulin; If this does not happen, then repeat the procedure, but not more 6 time. If insulin is not supplied from the needle, which indicates, that syringe pen is faulty and is not subject to further use.
Installation dose. Check, that the dosage selector is set to “0”. Dial the number of units, required for injection. The dosage can be adjusted by rotating the dosage selector in either direction. When rotating the selector clockwise dosage should be careful, not to accidentally press the start button, avoid the release of insulin dose. Set dose, exceeding the number of units, remaining in the cartridge, impossible.
The introduction of the drug. Enter the needle subcutaneously. To make an injection, press the start button all the way. With the introduction of the drug should only press the start button. After injection, the needle should be left under the skin on 6 sec. When removing the needle, hold the release button is fully pressed, This will ensure that the introduction of a full dose of the drug.
Removing the needle. Close the outer needle cap and unscrew it from the pen. Discard the needle, observing precautions. After each injection, the needle should be removed. Otherwise, at a differential temperature of the liquid may leak from the pen.
Medical staff, relatives and others who care for patients should follow the general rules of caution when removing and disposing of needles in order to avoid the risk of accidental needle stick.
Used Levemir® FlexPen® Discard the needle with detached.
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 alcohol, clean and lubricate it unnecessarily. it can damage the device. Avoid damage to the pen dispenser with Levemir® FlexPen®.
Adverse Reactions, observed in patients, applying Levemir® FlexPen®, are dose dependent and are mainly due to develop pharmacological effect of insulin. The most frequent side effect is hypoglycaemia, which develops when administered dose is too high relative to the body's need for insulin. From clinical investigations it is known, that severe hypoglycemia, defined as the need for intervention of third parties, develop approximately 6% patients, receiving Levemir® FlexPen®.
The proportion of patients, receiving treatment with Levemir® FlexPen®, which is expected to develop side effects, It is estimated as 12%. The incidence of side effects, which are related to the overall assessment of the drug Levemir® FlexPen®, during clinical trials, represented below.
Adverse Reactions, related to the effect on carbohydrate metabolism: often (>1%,<10%) – gipoglikemiâ, whose symptoms, usually, develop suddenly and may include pale skin, cold sweat, fatigue, nervousness, tremor, anxiety, unusual tiredness or weakness, disorientation, impaired concentration, drowsiness, pronounced hunger, blurred vision, Headache, nausea, heartbeat. Severe hypoglycemia may lead to unconsciousness and / or convulsions, temporary or permanent impairment of brain function or death.
Local reactions: in 2% cases – Local hypersensitivity reactions (redness, swelling and itching at the injection site), usually, are temporary, ie. disappear with continued treatment; rarely (>0.1%, <1%) – lipodystrophy (as a result of non-compliance with the rules of the change of the injection site within the same field).
Allergic reactions: rarely (>0.1%, <1%) – hives, skin rash, as well as generalized reaction – itching, increased sweating, disorders of the gastrointestinal tract, angioedema, difficulty breathing, tachycardia, decrease in blood pressure.
On the part of the organ of vision: rarely (>0.1%, <1%) – violation of refraction (usually it is temporary and occurs at the beginning of the treatment with insulin), diabeticheskaya retinopathy (long-term improved glycemic control decreases the risk of progression of diabetic retinopathy; However, intensification of insulin therapy with abrupt improvement in the control of carbohydrate metabolism may lead to a temporary deterioration of diabetic retinopathy).
From the nervous system: rarely (>0.01%, <0.1%) – perifericheskaya neuropathy, which is generally reversible. The rapid improvement in glycemic control may be associated with development of acute neuropathic pain, which is generally reversible.
Other: rarely (>0.1%, <1%) – swelling (occur in the early stages of insulin therapy and are usually temporary).
- Individual hypersensitivity to the drug.
Do not use the drug Levemir® FlexPen® in children aged 6 years, tk. clinical trials in these 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 a pregnancy and for the duration of pregnancy is necessary to conduct a thorough monitoring of patients with diabetes and control the level of glucose in the blood plasma. The need for insulin, usually, decreases in I trimester, and gradually increased in the II and III trimester of pregnancy. Shortly after birth, insulin requirements quickly return to the level, that was before pregnancy.
During the period of breast-feeding may be necessary to correct the dose and diet.
IN experimental studies animals not found differences between embryotoxic and teratogenic action of insulin detemir and human insulin.
Generalized allergic reactions are potentially life threatening.
In distinction from insulin Others, intensive therapy with Levemir® FlexPen® no increase in body weight.
Less compared with other insulins risk of nocturnal hypoglycemia allows you to carry out more intensive dose selection in order to achieve the target blood glucose.
Levemir® FlexPen® It provides better glycemic control (based on the measurement of fasting plasma glucose) compared with the use of insulin isophane. Lack of dose or discontinuation of treatment, particularly diabetes Type 1, can lead to hyperglycemia, or diabetic ketoacidosis. Usually, the first symptoms of hyperglycaemia appear gradually, for several hours or days. These symptoms include thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, acetone odor breath. In diabetes type 1 Without treatment 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 intense exercise may lead to hypoglycaemia.
After compensation of carbohydrate metabolism, eg, when intensified insulin therapy, patients can change their typical symptoms of hypoglycemia-precursors, what patients should be informed. Common symptoms-precursors may disappear with prolonged duration of diabetes.
Comorbidities, particularly infectious and accompanied by fever, usually increase the body's need for insulin.
Transfer the patient to a new type of drug or another manufacturer of insulin should be under strict medical supervision. If you change the concentration, Manufacturer, type, type (animal, human, analogs of human insulin) and / or the method of its production (genetically engineered insulin or animal origin) may require dose adjustment. Patients, going over treatment with Levemir® FlexPen®, may need to change the dose in comparison with the previously used doses of insulin. The need for dose adjustment may occur after the first dose, or during the first several weeks or months.
Levemir® FlexPen® should not be administered in /, t. to. it can lead to severe hypoglycemia.
If the drug Levemir® FlexPen® mixed with other insulin preparations, profile actions of one or both components of changes. Mixing Levemir drug® FlexPen® with fast insulin analog, such as insulin aspart, It leads to reduced activity profile and delayed maximum effect compared to their separate administration.
Levemir® FlexPen® It is not intended for use in insulin pumps.
Effects on ability to drive vehicles and management mechanisms
The patient's ability to concentrate and the reaction rate can be violated at the time of hypoglycemia and hyperglycemia, that may constitute a danger in situations, When these abilities are especially needed (eg, when driving or operating machines and mechanisms). Patients should be advised to take measures to prevent the development of hyperglycemia and hypoglycemia while driving and operating machinery. This is especially important for patients with absence or reduction in symptoms, precursors of developing hypoglycemia or frequent episodes of hypoglycemia sufferers. In these cases, you should consider the appropriateness of performing such work.
A certain dose, needed for an overdose of insulin is not installed, However, hypoglycaemia may develop gradually, if it introduced too high dose for a particular patient.
Treatment: light hypoglycaemia the patient can resolve itself, taking into glucose, sugar or carbohydrate-rich foods. Therefore, patients with diabetes should always carry sugar, confection, biscuits or sugary fruit juice.
In the case of severe hypoglycemia, when the patient is unconscious, enter from 0.5 to 1 glucagon mg / m or s / c (can be administered by trained persons), or in / dextrose solution (Glucose) (may enter only medical worker). It is also necessary in / dextrose when administered, if in 10-15 minutes after the administration of glucagon, the patient does not regain consciousness. After regaining consciousness of the patient is recommended to take food rich in carbohydrates to prevent the recurrence of hypoglycemia.
Hypoglycemic effect of insulin increase the oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, sulfonamides, anabolic steroid, tetracikliny, clofibrate, ketoconazole, meʙendazol, pyridoxine, theophylline, cyclophosphamide, fenfluramin, lithium preparations, preparations, containing ethanol.
Hypoglycemic effect of insulin impaired oral contraceptives, GCS, thyroid hormones, thiazide diuretics, Heparin, tricyclic antidepressants, sympathomimetic, danazol, klonidin, blockers slow calcium channels, diazoksid, morphine, phenytoin, nicotine.
Under the influence of reserpine and possibly as a weakening of salicylates, and strengthening of the drug.
Octreotide, lanreotide can either increase, and reduce the body's need for insulin.
Beta-blockers may mask the symptoms of hypoglycaemia and delay recovery from hypoglycemia.
Ethanol can enhance and prolong the hypoglycaemic effect of insulin.
The results of studies of protein binding in vitro and in vivo showed no clinically significant interaction between insulin detemir and fatty acids or other agents, binds to a protein.
Some medicines, eg, containing thiol or sulfite, when added to the drug Levemir® FlexPen®, can cause destruction of the insulin detemir. Levemir® FlexPen® should not be added to infusion solutions.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored in a refrigerator at 2 ° to 8 ° C (away from the freezing chamber); Do not freeze. Shelf life – 2 year.
To protect from light pen syringe should be stored while wearing the cap.
After the first use Levemir® FlexPen® It must not be stored in the refrigerator. Used or carried as a spare pen syringe with a drug Levemir® FlexPen® should be kept at a temperature no higher than 30 ° C for up to 6 weeks.
The drug should be stored out of reach of children.