Composition, form of production and packaging
Solution for injections is transparent, colorless.
1 ml of 1 fl.
Insulin soluble (human genetically engineered) 100 IU * 1000 IU *
Excipients: zinc chloride, glycerol, metacresol, sodium hydroxide and / or hydrochloric acid (to maintain the pH level), water d / u.
* 1 IU corresponds to 35 Ојg of anhydrous human insulin.
10 ml - bottles of glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
Actrapid NM is a short-acting insulin preparation produced by the method of biotechnology of recombinant DNA using the strain of Saccharomyces cerevisiae.Interacts with a specific receptor of the outer cytoplasmic cell membrane and forms an insulin-receptor complex. Through the activation of cAMP biosynthesis (in fat cells and liver cells) or directly penetrating the cell (muscles), the insulin-receptor complex stimulates intracellular processes, including the synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase, etc.). Reduction of blood glucose is due to increased intracellular transport, increased absorption and assimilation by tissues, stimulation of lipogenesis, glycogenogenesis, protein synthesis, decrease in the rate of production of glucose by the liver, etc.
The duration of action of insulin preparations is mainly due to the rate of absorption, which depends on several factors (for example, on the dose, method, site of administration and type of diabetes). Therefore, the profile of insulin action is subject to significant fluctuations, both in different people and in the same person.
The action of the drug Actrapid NM begins within half an hour after administration, and the maximum effect is manifested within 1.5-3.5 hours, with a total duration of action of about 7-8 hours.
Completeness of absorption and the beginning of the effect of insulin depends on the mode of administration (subcutaneously, intramuscularly), the injection site (abdomen, thigh, buttocks), the dose (volume of insulin administered), the concentration of insulin in the preparation, etc. The maximum concentration (C max ) of insulin in plasma is achieved for 1.5-2.5 hours after subcutaneous administration. Distribution
Expressed binding to plasma proteins is not observed, sometimes only circulating antibodies to insulin are detected.
Human insulin is cleaved by insulin protease or insulin-degrading enzymes, and possibly also by protein disulfide isomerase. It is assumed that in the human insulin molecule there are several cleavage sites (hydrolysis); but none of the metabolites formed due to the cleavage is active.
The half-life (T 1/2 ) is determined by the rate of absorption from the subcutaneous tissues. Thus, T 1/2 is rather a measure of absorption, and not actually a measure of insulin release from the plasma (T 1/2 of insulin from the bloodstream is only a few minutes). Studies have shown that T 1/2 is about 2-5 hours.
Pharmacokinetics in special clinical cases
The pharmacokinetic profile of the drug Actrapid NM was studied in a small group of children with diabetes mellitus (18 people) aged 6-12 years, as well as adolescents (aged 13-17 years). Although the data obtained are considered to be limited, they nevertheless showed that the pharmacokinetic profile of the drug Actrapid NM in children and adolescents is similar to that of adults. At the same time, differences between different age groups were revealed by the indicator such as C max , which once again emphasizes the need for individual dose selection.
- Urgent conditions in patients with diabetes mellitus, accompanied by a violation of glycemic control.
The drug is intended for p / to and / in the introduction.
The dose of the drug is selected individually, taking into account the needs of the patient. Typically, the need for insulin is 0.3 to 1 IU / kg / day. Daily need for insulin may be higher in patients with insulin resistance (eg, during puberty, as well as in obese patients), and lower in patients with residual endogenous insulin production.
If patients with diabetes mellitus achieve optimal control of glycemia, then complications of diabetes, they usually appear later. In this regard, we should strive to optimize metabolic control, in particular, by carefully monitoring the level of glucose in the blood.
Actrapid HM is a short-acting insulin and can be used in combination with long-acting insulins.
The drug is administered 30 minutes before a meal or a light snack containing carbohydrates.
Actrapidum HM is usually injected sc, into the region of the anterior abdominal wall. If it is convenient, then injections can be done also in the thigh area, in the gluteal region or in the area of вЂ‹вЂ‹the deltoid muscle of the shoulder. When the drug is injected into the anterior abdominal wall, a faster absorption is achieved than when injected into other areas. Execution of an injection in the skin fold reduces the risk of getting into the muscle.
It is necessary to change the injection site within the anatomical area to prevent the development of lipodystrophy.
In / m injections are also possible, but only for the doctor's prescription.
Actrapid NM can also be administered iv, and such procedures can only be performed by a medical professional.
Correction of dose
With the defeat of the kidneys or liver, the need for insulin decreases.
Instructions for use and handling of the drug
For intravenous administration infusion systems containing the drug Actrapid HM 100 IU / ml, in concentrations from 0.05 IU / ml to 1 IU / ml human insulin in infusion solutions, such as 0.9% sodium chloride solution, 5% and 10% dextrose solutions, including potassium chloride at a concentration of 40 mmol / l; in the system for intravenous administration, infusion bags made of polypropylene are used; these solutions are stable for 24 hours at room temperature.
Although these solutions remain stable for a certain period of time, an initial absorption of some insulin with the material from which the infusion bag is made is noted. During the infusion it is necessary to monitor the blood glucose level.
Instructions on the use of Actrapid NM, which must be given to the patient.
Vials with the drug Actrapid NM can Use only together with insulin syringes, which have a scale that allows you to measure the dose in units of action. The vials with the drug Actrapid NM are intended only for individual use.
Before using Actrapid В® HM it is necessary: вЂ‹вЂ‹вЂў Check the label to make sure that the correct type of insulin is selected; to disinfect the rubber plug with a cotton swab.
The drug Actrapid В® HM can not be used in the following cases:
- in insulin pumps;
- patients need to explain that if on a new, just received from a pharmacy vial, there is no protective cap or it sits loosely - such insulin should be returned to the pharmacy;
- if the insulin was stored incorrectly, or if it was frozen.
- if insulin has ceased to be transparent and colorless.
If the patient uses only one type of insulin
1.Set the air in the syringe in the amount corresponding to the desired dose of insulin.
2. Insert air into the vial with insulin. To do this, the needle is pierced with a rubber plug and press the plunger.
3. Turn the bottle with the syringe upside down.
4. Type the desired the dose of insulin in the syringe.
5. Remove the needle from the vial.
6. Remove air from the syringe.
7. Check if the insulin dose is correct.
8. Immediately inject.
If the patient needs to mix ActrapidВ® HM with long-acting insulin
1. Roll a vial of long-acting insulin ("cloudy") between the palms until the insulin becomes evenly white and cloudy.
2. Draw in the syringe air in an amount corresponding to the dose of "turbid" insulin. Enter the air into the bottle with a "cloudy" insulin and remove the needle from the bottle.
3. Draw in the syringe air in an amount corresponding to the dose of the drug Actrapid NM ("transparent"). Enter the air into the vial from the drug Actrapid NM.
4. Turn the bottle with the syringe ("transparent") upside down and dial the desired dose of the drug Actrapid NM. Remove the needle and remove air from the syringe. Check the correctness of the dialed dose.
5. Insert the needle into the vial with "turbid" insulin.
6. Turn the bottle with the syringe upside down.
7. Dial the required dose of "cloudy" insulin.
8. Remove the needle from the vial.
9. Remove air from the syringe and check the correctness of the dialed dose.
10. Immediately inject the dialed insulin mixture with a short and
Always take short and long-acting insulin in the same sequence described above.
Instruct patient how to inject insulin
1. With two fingers, take a skin fold, insert the needle into the base of the fold at an angle of about 45 degrees and insert insulin under the skin.
2. After the injection, the needle should remain under the skin for at least 6 seconds, in order to ensure that the insulin is injected completely.
Adverse reactions observed in patients on the background of therapy with the drug Actrapid NM were predominantly dose-dependent and were due to pharmacological action insulin. As with the use of other insulin preparations, the most common side effect is hypoglycemia. It develops in cases, when the dose of insulin significantly exceeds the need for it. In clinical trials, as well as during the use of the drug after its release to the consumer market, it was found that the incidence of hypoglycemia varies between different patient populations and with different dosing regimens, so it is not possible to indicate exact frequency values.
In severe hypoglycemia, loss of consciousness and / or convulsions may occur, temporary or permanent impairment of brain function and even death may occur.Clinical studies have shown that the incidence of hypoglycemia as a whole did not differ between patients receiving human insulin and those receiving insulin aspart.
Below are the values вЂ‹вЂ‹of the incidence of adverse reactions identified in a clinical trial, which were regarded as associated with the use of the drug Actrapid NM. The frequency was determined as follows: infrequently (> 1/1000, <1/100); very rarely (<1/10000), including isolated spontaneous cases.
Disorders from the immune system: infrequently - urticaria, rash; very rarely - anaphylactic reactions. Symptoms of generalized hypersensitivity may include generalized cutaneous rash, itching, sweating, abnormalities on the part of the digestive tract, angioedema, dyspnea, palpitations, decreased blood pressure, fainting / loss of consciousness. Generalized hypersensitivity reactions can pose a threat to life.
Disorders from the nervous system: very rarely - peripheral neuropathy. If the improvement in blood glucose control was achieved very quickly, a condition called "acute painful neuropathy", which is usually reversible, can develop.
Disturbances from the side of the organ of vision: infrequent refractive error. Refractive disorders are usually noted at the initial stage of insulin therapy. As a rule, these symptoms are reversible. Very rarely - diabetic retinopathy. If the glycemia is adequately controlled for a long time, then the risk of progressing diabetic retinopathy is reduced. However, the intensification of insulin therapy with a sharp improvement control of glycemia may lead to a temporary increase in the severity of diabetic retinopathy.
Disturbances from the skin and subcutaneous tissues: infrequently - lipodystrophy. Lipodystrophy can develop at the site of injections in the event that there is no permanent change of the injection site within one area of вЂ‹вЂ‹the body.
Disturbances on the part of the body as a whole, as well as reactions at the injection site: infrequent reactions at the site of injection. On the background of insulin therapy, reactions can occur at the site of the injection (redness of the skin, swelling, itching, soreness, the formation of a hematoma at the site of the injection).However, in most cases, these reactions are transitory and disappear during the continuation of therapy. Infrequent - puffiness. Puffiness is usually noted at the initial stage of insulin therapy. As a rule, this symptom is transient.
- hypersensitivity to human insulin or to any component that is part of this drug.
PREGNANCY AND LACTATION
Limitations on the use of insulin during pregnancy does not exist, because insulin does not penetrate the placental barrier. Moreover, if you do not carry out diabetes treatment during pregnancy, then there is a danger to the fetus. Therefore, diabetes should be continued during pregnancy.
Both hypoglycemia and hyperglycemia, which can develop in cases of inadequately selected therapy, increase the risk of developing fetal malformations and fetal death. Pregnant women with diabetes should be under observation throughout pregnancy, they need to exercise increased blood glucose control; the same recommendations apply to women who are planning a pregnancy.
The need for insulin usually decreases in the first trimester of pregnancy and gradually increases in the second and third trimesters.
After delivery, the need for insulin quickly returns to the level that was noted before pregnancy.
There are also no restrictions for the use of the drug Actrapid NM in the period of breastfeeding. Carrying out insulin therapy for breastfeeding mothers does not pose a danger to the child. However, the mother may need to adjust the dosage regimen of the drug Actrapid NM and / or diet.
APPLICATION FOR FUNCTIONS OF THE LIVER
With kidney damage, the need for insulin decreases.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With liver damage, the need for insulin decreases.
With improperly selected doses or with the withdrawal of therapy, hyperglycemia may develop, especially in patients with type 1 diabetes. The first symptoms of hyperglycemia usually appear gradually, within a few hours or days. Such symptoms include nausea, vomiting, pronounced drowsiness, reddened, dry skin, dry mouth, increased urine output, thirst, loss of appetite, and the smell of acetone from the mouth.
If you do not carry out treatment Hyperglycemia in type 1 diabetes mellitus can lead to the development of life-threatening diabetic ketoacidosis. In cases of significant improvement in glycemic control, for example, due to intensified insulin therapy, habitual symptoms-precursors of hypoglycemia may also change, which patients should be warned about.
With concomitant diseases, especially with infections and febrile conditions, the need for patients in insulin usually increases.
If a patient is transferred from one type of insulin to another, then early symptoms, precursors of hypoglycemia, may change or become less pronounced than those noted with the administration of the preceding insulin.
The transfer of patients to another type of insulin or to the insulin of another manufacturer must be carried out only under medical supervision. When changing biological activity, changing the manufacturer, type, species (animal, human, human insulin analog) and / or manufacturing method, a change in the dosage regimen may be required.
If dose adjustment is necessary, this can be done already with the administration of the first dose or in the first weeks or months of therapy.
Skipping meals or unplanned heavy physical activity can cause hypoglycemia.
If the patient is to travel through the intersection of time zones, then he should consult a doctor, because he will have to change the time of insulin administration and eating.
When the drug Actrapid NM is added to the infusion solutions, the amount of insulin absorbed by the infusion system is unpredictable, so the use of Actrapid NM in PPII is not allowed.
The composition of the drug Actrapid NM is metarekzol, which can cause allergic reaction.
Influence on the ability to drive and work with machinery
The ability of patients to concentrate and respond may disturbed during hypoglycemia and hyperglycemia, which can be dangerous in those situations, when these abilities are especially necessary (for example, when driving a car or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia when driving a car and working 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, you should consider the advisability of driving.
Preclinical safety data
In preclinical studies, including toxicity studies with repeated dosing studies of genotoxicity, carcinogenic potential and reproductive toxicity scope, specific risk to humans has not been revealed.
The specific dose when administered which could speak of an overdose of insulin, is not set, however, in cases where patients are administered a dose is too high, exceeding their needs, may develop the state of hypoglycemia of varying severity.
Easy hypoglycaemia the patient can remove himself, taking into sugar or carbohydrate-rich foods. Therefore, patients with diabetes should always carry sugar, sweets, biscuits or sugary fruit juice.
In severe cases, a patient with loss of consciousness, in / injected 40% dextrose (glucose); V / m, n / k - glucagon (0.5-1 mg). After recovery of consciousness patient is recommended to take food rich in carbohydrates, to prevent recurrence of hypoglycemia.
There are a number of drugs that affect the need for insulin.
Hypoglycemic effect of insulin enhance oral hypoglycemic agents, monoamine oxidase inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, selective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, klofiorat, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium, drugs, containing ethanol.
Hypoglycemic effect of insulin impaired oral contraceptives, corticosteroids, thyroid hormone, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.
Under the influence of reserpine and salicylates may as weakening or strengthening of the drug.
Beta-blockers may mask the symptoms of hypoglycaemia and hamper the elimination of hypoglycemia.
Octreotide / lanreotide may either decrease or increase the need for insulin.
Alcohol may intensify and lengthen the hypoglycemic effect of insulin.
Actrapid HM can be added only to those compounds with which it is known to be compatible. Several drugs (e.g., formulations containing thiols or sulfites), when added to the insulin solution may cause its degradation.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Keep refrigerated at 2 В° C to 8 В° C (not too close to the freezer) in the carton box. Do not freeze. The drug should be protected from exposure to heat and sunlight.Keep out of the reach of children. Shelf life - 30 months. Do not use after expiry date.
For opening the bottle: stored at a temperature not higher than 25 В° C for 6 weeks. Do not store in the refrigerator. Keep the bottle in the carton box for protection from light.