Insulin detemir

When ATH: A10AE05

Pharmacological action

Modern recombinant DNA technology have improved the profile of a simple action (regular) insulin. Insulin detemir is produced by biotechnology Recombinant DNA using strain Saccharomyces cerevisiae, It is a soluble analog of human basal insulin with a prolonged action profile of action Thus, the peakless. Avatar actions are much less compared with variabelen isophane insulin and insulin glargine. Prolonged effect of self-association is due to a pronounced insulin detemir molecules at the injection site and the binding of molecules to albumin through a connection with a side-chain fatty acid. Insulin detemir compared with isophane insulin in peripheral target tissues distributed slower. These combined mechanisms of delayed distribution profile gives a more reproducible absorption and action of insulin detemir. Insulin detemir is characterized by a much greater predictability intraindividualnoy patients compared with NPH insulin or insulin glargine. Said predictability caused by two factors: insulin detemir remains dissolved in all phases of its formulation and to bind with the insulin receptor and the effect of binding buffer with serum albumin.

Pharmacokinetics

By interaction with a specific receptor outer plasma membrane of cells, forms of insulin-receptor complex, stimulating intracellular processes, including the synthesis of a number of key enzymes (geksokinaza, pyruvate, glikogensintetazy and others.). 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, etc.. For a dose of 0.2-0.4 U / kg 50% maximum effect occurs in the range of 3-4 hours before 14 hours after injection. After subcutaneous administration was observed pharmacodynamic response, proportional to the administered dose (maximum effect, duration, cumulative effect). After s / c injection of detemir binds to albumin through its fatty acid chain. Thus, in the state of stable concentration of free unbound action of insulin significantly reduced, which leads to a stable level of glucose. The duration of a dose of detemir 0,4 U / kg - about 20 no, and the drug is administered twice a day for most patients. In long-term studies ( 6 Months) figure glucose fasting plasma in patients with type I diabetes was better than isophane insulin, appointed to the basis / bolus therapy. Glycemic control (гликозилированный гемоглобин — HbA1c) against the background of insulin detemir was comparable to that in the treatment of insulin isophane, with a lower risk of nocturnal hypoglycaemia and no increase in body weight compared to his application. Profile Night glucose control is more flat and smooth in the insulin detemir compared with isophane insulin, which is reflected in a lower risk of nocturnal hypoglycemia.

Insulin detemir maximum concentration in serum is attained after 6-8 hours after administration. When twice daily regimen of administration stable drug concentration in serum is achieved after 2-3 injections.

Inactivation similar to that in preparations of human insulin; all metabolites formed are inactive. Results of studies of binding proteins in vitro and in vivo showed no clinically significant interactions between insulin detemir and fatty acids or other agents, Associated with the blood.

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

When s / to a serum concentrations were proportional to the administered dose (maximum concentration, the extent of absorption).

Special groups of patients

Pharmacokinetic properties were investigated in children (6-12 Years) and adolescents (13-17 Years) and compared with adults with diabetes type I. differences in pharmacokinetic properties were found. No clinically significant differences in the pharmacokinetics of insulin detemir between elderly and younger patients, or between patients with impaired renal and hepatic function, and healthy patients were found.

Testimony

Diabetes.

Dosage regimen

It is intended for subcutaneous administration. The dose is determined individually in each case. Insulin detemir should be used 1 or 2 times a day based on the patient's needs. Patients, which requires the use of twice a 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. Insulin detemir is injected s / c in the thigh area, the anterior abdominal wall or shoulder. Injection sites should be changed even when administered in the same region. As with other insulins, in elderly patients and patients with renal or hepatic impairment should be more carefully monitored blood glucose and insulin detemir corrected individually. Dose adjustment may also be required and enhance the physical activity of the patient, change its usual diet or during concomitant diseases.

Contraindications

Increased individual sensitivity to insulin detemir or any of its komponentov.Ne recommended for use in children under 6 years, since clinical studies in children younger 6 years have not been conducted.

Side effect

Adverse Reactions, observed in patients, using insulin detemir are generally dose-related and develop due to the pharmacological effect of insulin. Gipoglikemiâ, usually, It is the most common side effect. Hypoglycemia occurs when the, If too high a dose of the drug with respect to the body's need for insulin.

Injection site reactions can be observed in the treatment of approximately 2% patients. The proportion of patients, treated and who are expected to develop side effects, It is estimated as 12%. The incidence of adverse events during clinical trials, represented below.

Disorders of metabolism and nutrition disorders: frequent (1/100, ≤1/10).

Gipoglikemiâ: Symptoms of hypoglycaemia usually develop suddenly. These include a "cold sweat", pale skin, fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, disorientation, poor 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.

General disorders and reactions to the injection site: frequent (1/100, ≤1/10).

Reactions at the injection site: Local hypersensitivity reactions (redness, swelling and itching at the injection site) may develop during treatment with insulin. These reactions are usually short-lived and disappear with continued treatment.

Few (1/1000, ≤1/100).

Lipodystrophy: It may develop at the injection site as a result of non-compliance with the rules of the change of the injection site within the same field. Swelling: may occur in the early stages of insulin. These symptoms are usually temporary.

Disorders of the immune system: few (1/1000, ≤1/100).

Allergic reactions: hives, skin rash may develop as a result of hypersensitivity. Signs of hypersensitivity may be itching, Sweating, gastrointestinal disorders, angioedema, difficulty breathing, heartbeat, decrease in blood pressure. The development of hypersensitivity reactions may be potentially life-threatening.

Violations of visual function: few (1/1000, ≤1/100).

Refractive errors: refractive errors can occur in the early stages of insulin. These symptoms are usually temporary. 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 the temporary strengthening signs of diabetic retinopathy.

Disorders of the nervous system: very rare (1/10000, ≤1/1000).

Peripheral neuropathy: rapid improvement in glycemic control may lead to a state of acute painful neuropathy, which is generally reversible.

Cautions

Insulin detemir provides better glycemic control (by measuring the fasting plasma glucose) compared with isophane insulin. Insufficient insulin dose or discontinuation of treatment, particularly diabetes type I, 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 Type I diabetes 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 insulin needs for a particular patient. Skipping meals or intensive physical activity may lead to hypoglycaemia. After compensation of carbohydrate metabolism, such as 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.

Translation from other types of insulin

Transfer the patient to a new type of insulin or insulin another manufacturer should take place 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 insulin detemir, may need to change the dose in comparison with the previously used dose of insulin. The need for correction of the dosage may already after the first dose, or during the first several weeks or months. Insulin detemir should not be administered in /, as this may lead to a state of severe hypoglycemia. Absorption at / m administration is faster and to a greater extent as compared with subcutaneous administration. If insulin detemir is mixed with other types of insulin, profile actions of one or both components of changes. Mixing of insulin detemir with fast insulin analog, such as insulin aspart, It leads to reduced activity profile and delayed maximum effect compared to their separate administration.

Translation from intermediate-acting insulin and long-acting insulin to insulin Levemir may require correction of the dose and timing of administration. As with other insulins, we recommend careful monitoring of blood glucose levels during the transfer and in the first week of the appointment of a new insulin. Maybe, need correction of concomitant hypoglycemic therapy (dose and time of administration of insulin types of short-range or the dose of oral hypoglycemic agents).

Insulin detemir is not intended for use in insulin pumps.

Pregnancy and lactation

Currently, there are no data of clinical use of insulin detemir during pregnancy and lactation. Reproduction studies in animals did not reveal any differences between insulin detemir and human insulin in terms of embryotoxicity and teratogenicity. Generally, careful observation of pregnant women, diabetes during the pregnancy, as well as planning pregnancy. Insulin requirements in the I trimester of pregnancy usually decreases, then in the II and III trimester increases. Shortly after birth, insulin requirements quickly return to the level, that was before pregnancy. In women, breast-feeding may require dose adjustment of inulin and diet.

Effects on ability to drive a car and operate machinery

The patient's ability to concentrate and the reaction rate can be violated at the time of hypoglycemia or 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. In these cases, you should consider the advisability of driving or performing such work.

Drug Interactions

There are several drugs, that affect the demand for insulin.

Hypoglycemic effect of insulin increase: oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, неселективные b-адреноблокаторы, 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 may either increase, and reduce the body's need for insulin. Β-adrenergic blockers may mask the symptoms of hypoglycaemia and delay recovery from hypoglycemia. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

Incompatibility

Some medicines, eg, containing thiol or sulfite, adding to a solution of insulin detemir, can cause its destruction. Therefore it is not necessary to add insulin detemir infusion r-ry.

Overdose

A certain dose, lets talk about an overdose of insulin is not installed, However, hypoglycaemia may develop gradually, if it introduced too high dose for a particular patient. Symptoms of hypoglycemia.

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 0.5-1 mg of glucagon / m or s / c, (can be administered by trained persons), or in / rr dextrose (Glucose)(may enter only medical worker). You also need to / vennoe introduction of dextrose in the case, If after 10-15 minutes after administration of glucagon, the patient does not regain consciousness. After regaining consciousness of the patient it is recommended to take food, rich in carbohydrates to prevent recurrent hypoglycaemia.