Levemir Flexpen solution for n / a injection 100 units / ml, 3ml No. 5 syringe-pen

Inject s / c into the thigh, anterior abdominal wall or shoulder. It is necessary to change injection sites within the anatomical region to prevent the development of lipodystrophy. Insulin will act faster if it is injected into the anterior abdominal wall.

Administered 1 or 2 times / day based on the patient's needs. Patients who require the use of the drug 2 times / day for optimal glycemic control can enter the evening dose either during dinner, or before bedtime, or 12 hours after the morning dose.

Elderly patients, as well as with impaired liver and kidney function, should be more closely monitored blood glucose levels and adjust the dose of insulin.

A dose adjustment may also be required if the patient is more physically active, changes his usual diet, or if there is a concomitant illness.

When transferring from insulins of intermediate duration and prolonged-acting insulins to insulin detemir, dose and time of administration may need to be adjusted. Careful monitoring of blood glucose levels during transfer and in the first weeks of treatment with insulin detemir is recommended. Correction of concomitant hypoglycemic therapy (dose and timing of short-acting insulin preparations or oral hypoglycemic drugs dose) may be required.

The solution for subcutaneous administration is transparent, colorless.

1 ml insulin detemir 100 UNITS *

Excipients: glycerol - 16 mg, phenol - 1.8 mg, metacresol - 2.06 mg, zinc acetate - 65.4 ?g, sodium hydrogen phosphate dihydrate - 0.89 mg, sodium chloride - 1.17 mg, hydrochloric acid or sodium hydroxide - qs, water d / i - up to 1 ml.

Increased individual sensitivity to insulin detemir.

pharmachologic effect

Long-acting insulin, a soluble analogue of human insulin. Produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain.

The prolonged action is due to the pronounced self-association of the insulin detemir molecules at the injection site and the binding of the drug molecules to albumin through the connection with the side chain. Insulin detemir is delivered to peripheral target tissues more slowly than insulin isophane. These combined mechanisms of delayed distribution provide a more reproducible absorption and action profile of insulin detemir compared to insulin isophane.

Interacts with a specific receptor of the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase).

A decrease in blood glucose is due to an increase in its intracellular transport, increased assimilation by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver.

At doses of 0.2-0.4 U / kg 50%, the maximum effect 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.

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

The nocturnal glucose control profile is flatter and smoother for insulin detemir compared to insulin isophane, which is reflected in a lower risk of nocturnal hypoglycemia.

Pharmacokinetics

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

Side effect

Adverse reactions associated with the effect on carbohydrate metabolism: often - hypoglycemia, the symptoms of which usually develop suddenly and may include pallor of the skin, cold sweat, increased fatigue, nervousness, tremors, anxiety, unusual fatigue or weakness, disorientation, impaired concentration attention, drowsiness, severe hunger, visual impairment, headache, nausea, palpitations. Severe hypoglycemia can lead to loss of consciousness and / or seizures, temporary or irreversible dysfunction of the brain, or even death.

Adverse reactions at the injection sites: often - reactions of local hypersensitivity (redness, swelling and itching at the injection site), as a rule, are temporary in nature, i.e. disappear with continued treatment; rarely - lipodystrophy (as a result of non-compliance with the rule of changing the injection site within the same area).

Allergic reactions: rarely - urticaria, skin rash, as well as generalized reactions - itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, decreased blood pressure.

On the part of the organ of vision: rarely - refractive error (usually temporary and observed at the beginning of insulin treatment), diabetic retinopathy (long-term improvement in glycemic control reduces the risk of diabetic retinopathy progression; however, intensification of insulin therapy with a sharp improvement in control of carbohydrate metabolism can lead to a temporary worsening of the condition diabetic retinopathy).

From the nervous system: in some cases - peripheral neuropathy, which is usually reversible.

Others: rarely - edema.

Application during pregnancy and lactation

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

During the period of possible onset and throughout the entire period of pregnancy, it is necessary to closely monitor the condition of patients with diabetes mellitus and control the level of glucose in the blood plasma. The need for insulin, as a rule, decreases in the first trimester and gradually rises in the second and third trimesters of pregnancy. Soon after childbirth, the need for insulin quickly returns to pre-pregnancy levels.

During breastfeeding, it may be necessary to adjust the dose of the drug and diet.

In experimental animal studies, no differences were found between the embryotoxic and teratogenic effects of insulin detemir and human insulin.

Application for violations of liver function

In case of impaired liver function, blood glucose levels should be more closely monitored and the dose of insulin adjusted.

Application for impaired renal function

In case of impaired renal function, blood glucose levels should be more closely monitored and the dose of insulin adjusted.

Application in children

It is not recommended to use insulin detemir in children under 6 years of age.

Use in elderly patients

In elderly patients, blood glucose levels should be more closely monitored and the dose of insulin adjusted.

special instructions

It is not recommended to use insulin detemir in children under 6 years of age.

It is believed that intensive therapy with insulin detemir does not lead to an increase in body weight.

The lower risk of nocturnal hypoglycemia compared to other insulins allows for more intensive dose selection in order to achieve the target blood glucose level.

Insulin detemir provides better glycemic control (based on fasting plasma glucose measurements) compared to insulin isophane. An insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes mellitus, can lead to the development of hyperglycemia or diabetic ketoacidosis. As a rule, the first symptoms of hyperglycemia appear gradually, over several hours or days. These symptoms include thirst, increased urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone in the breath. In type 1 diabetes mellitus without appropriate treatment, hyperglycemia leads to the development of diabetic ketoacidosis and can be fatal.

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

Skipping meals or unplanned strenuous exercise can lead to hypoglycemia.

After compensation of carbohydrate metabolism, for example, with intensified insulin therapy, patients may change their typical symptoms, precursors of hypoglycemia, about which patients should be informed. The usual precursor symptoms can disappear with prolonged diabetes mellitus.

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

Transfer of a patient to a new type or preparation of insulin from another manufacturer should be carried out under strict medical supervision. If the concentration, manufacturer, type, species (animal, human, analogs of human insulin) and / or method of its production (genetically engineered or animal insulin) changes, dose adjustment may be required.

Insulin detemir should not be given IV as it can lead to severe hypoglycemia.

Mixing insulin deremir with a fast-acting insulin analog such as insulin aspart results in an action profile with a reduced and delayed maximum effect compared to their separate administration.

Influence on the ability to drive vehicles and use mechanisms

The ability of patients to concentrate and reaction speed can be impaired during hypoglycemia and hyperglycemia, which can be dangerous 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 the development of hypoglycemia and hyperglycemia while driving and operating machinery. This is especially important for patients with no or decreased severity of symptoms, precursors of developing hypoglycemia or suffering from frequent episodes of hypoglycemia. In these cases, the advisability of performing such work should be considered.

Drug interactions

The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, drugs, ketoconazole, meboxinendazolum, drugs containing ethanol. The hypoglycemic effect of insulin is weakened by oral contraceptives, GCS, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, slow calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.

Under the influence of reserpine and salicylates, both weakening and strengthening of the action of insulin detemir 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 from hypoglycemia.

Ethanol can enhance and prolong the hypoglycemic effect of insulin.

Pharmaceutical interactions

Certain drugs, such as those containing a thiol or sulfite, when added to insulin detemir, can cause the detemir to break down insulin.