Actrapid HM - instructions for use, dosage, adverse effects, contraindications

Excipients: zinc 7 μg (in the form of zinc chloride), glycerol (glycerol) 16 mg, metacresol 3.0 mg, sodium hydroxide about 2.6 mg and / or hydrochloric acid about 1.7 mg (for adjustment pH), water for injection up to 1.0 ml.

1 bottle contains 10 ml of the drug, which corresponds to 1000 ME,

1 syringe-pen contains 3 ml of the drug, which corresponds to 300 ME.

Description:

A clear, colorless liquid.

Pharmacotherapeutic group:Hypoglycemic agent - short-acting insulin

ATX: & nbsp

A.10.A.B.01 Insulin (human)

Pharmacodynamics:

Actrapid® NM is a short-acting insulin preparation produced by the biotechnology of recombinant DNA using a strain Saccharomyces cerevisiae.

Reducing the concentration of glucose in the blood is due to increased intracellular transport after the binding of insulin with insulin receptors of muscle and adipose tissue and a simultaneous decrease in the rate of glucose production by the liver.

Normalization of plasma glucose concentration (up to 4.4-6.1 mmol / L) with intravenous injection of the drug Actrapid® NM in patients of intensive care unit,(204 patients with diabetes mellitus and 1344 patients without diabetes mellitus) who had hyperglycemia (plasma glucose concentration> 10 mmol / L), reduced mortality by 42% (4.6% instead of 8%).

The action of the drug Actrapid® HM 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.

Pharmacokinetics:

The half-life of insulin from the bloodstream is only a few minutes. 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 of insulin, the method and place of administration, the thickness of the subcutaneous fat layer and the type of diabetes mellitus). Therefore, the pharmacokinetic parameters of insulin are subject to significant inter- and intra-individual fluctuations.

Suction

The maximum concentration (C_mOh) of insulin in plasma is achieved within 1.5-2.5 hours after subcutaneous administration.

Distribution

YouThere is no marked binding to plasma proteins, with the exception of circulating antibodies to insulin (if any).

Metabolism

Human insulin is cleaved by insulinase or insulin-cleavage enzymes, and possibly also by the action of protein disulfide isomerase.

It is assumed that there are several cleavage sites (hydrolysis) in the human insulin molecule, but none of the metabolites formed as a result of the cleavage is active.

Excretion

The half-life (T_1/2) is determined by the rate of absorption from the subcutaneous tissues. Thus, T_1/2 rather, it is a measure of absorption, and not actually a measure of insulin release from the plasma (T_1/2 insulin from the bloodstream is only a few minutes). Studies have shown that T_1/2 is about 2-5 hours.

Children and teens

The pharmacokinetic profile of Actrapid® NM was studied in a small group of children with diabetes (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 Actrapid® NM in children and adolescents is similar to that in adults. At the same time, differences were found between different age groups for such an indicator as C_max, which once again emphasizes the need for individual dose selection.

Pre-clinical safety data

During preclinical studies that included pharmacological safety studies, toxicity studies on repeated dose administration, genotoxicity studies, carcinogenic potential and toxic effects on the reproductive field, no specific human risk was identified.

Indications:

Diabetes mellitus, which needs insulin therapy.

Urgent conditions in patients with diabetes mellitus, accompanied by a violation of glycemic control.

Contraindications:

Hypoglycemia.

Hypersensitivity to human insulin or to any component that is part of this drug.

Pregnancy and lactation:

Pregnancy

There are no restrictions on the use of insulin during pregnancy, because insulin does not penetrate the placental barrier.

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 throughout pregnancy should be monitored,they need to exercise increased control of the concentration of glucose in the blood; 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, as a rule, quickly returns to the level that was noted before pregnancy.

Breastfeeding period

There are also no restrictions for the use of the drug Actrapid® HM in the period of breastfeeding. Carrying out insulin therapy for women during breastfeeding is not a danger to the child. However, it may be necessary to adjust the dosage regimen of Actrapid® HM and / or diet.

Dosing and Administration:

The drug is intended for subcutaneous and intravenous administration.

The dose of the drug is selected individually, taking into account the needs of the patient.

Usually the need for insulin is 0.3 to 1 IU / kg / day. The daily requirement for insulin may be higher in patients with insulin resistance (for example, during puberty, as well as in obese patients), and lower in patients with residual endogenous insulin production.

The drug is administered 30 minutes before a meal or a light snack containing carbohydrates. The drug Actrapid® HM is a short-acting insulin and can be used in combination with long-acting insulins.

The drug Actrapid® HM is usually administered subcutaneously, into the anterior abdominal wall area. If it is convenient, then injections can be done also in the thigh area, in the gluteal region or in the area of 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.

If the injection is made into a stretched skin fold, the risk of accidental intramuscular injection of the drug is minimized. The needle should remain under the skin for at least 6 seconds, which guarantees a complete dose. It is necessary to constantly change the injection site within the anatomical area to reduce the risk of lipodystrophy.

Intramuscular injections are also possible, but only for the doctor's prescription.

The drug Actrapid® HM can also be administered intravenously and such procedures can only be performed by a medical professional.

The drug Actrapid® NM in vials can only be used together with insulin syringes, which have a scale that allows measuring the dose of insulin in units of action.

Intravenous injection of the drug Actrapid® HM from the cartridge or syringe-pen is allowed only as an exception in the absence of vials. In this case, you should recruit Actrapid® HM in an insulin syringe without an air kit or infusion with an infusion system. This procedure should be performed only by a medical professional.

The FlexPen® syringe pen is a pre-filled syringe pen designed for use with NovoFine® or NovoTvist® disposable needles up to 8 mm long. The FlexPen® syringe pen allows you to enter a dose of 1 to 60 ME in increments of 1 ME.

Detailed recommendations for the use and administration of the drug should be observed (see "Actrapid® NM Solution for Injections in Vials." Instructions for Use for Patients "or" Actrapid® NM Solution for Injections in FlexPen® Syringe Pens. use for patients ").

Correction of dose

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

Correction of the dose of the drug may also be required if the patient has concomitant diseases of the kidneys, liver, adrenal, pituitary or thyroid gland disorders.

The need for dose adjustment can also occur when the physical load or the patient's normal diet changes. Correction of the dose may be required when transferring a patient from one type of insulin to another.

Side effects:

The most common side effect with insulin is hypoglycemia. 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 depending on the patient population, the dosage regimen of the drug and the control of glycemia. "Description of individual adverse reactions").

At the initial stage of insulin therapy, refractive disorders, peripheral edema and reactions at the injection site (including pain, redness, urticaria, inflammation, hematoma, swelling and itching at the injection site) may occur. These symptoms are usually temporary.Rapid improvement in glycemic control can lead to a state of "acute pain neuropathy," which is usually reversible.

Intensification of insulin therapy with a sharp improvement in carbohydrate metabolism control may lead to a temporary deterioration in the state of diabetic retinopathy, while a prolonged improvement in glycemic control reduces the risk of progression of diabetic retinopathy.

The list of side effects is presented in the table.

All of the side effects presented below, based on data from clinical trials, are grouped according to the frequency of development according to McDDRA and organ systems. The incidence of side effects is defined as: very often (≥ 1/10); often (≥ 1/100 to <1/10); infrequently (≥1 / 1,000 to <1/100); rarely (≥1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000) and unknown (impossible to estimate based on available data).

Immune system disorders	Infrequent - hives, skin rash
Immune system disorders	Very rarely - anaphylactic reactions *
Disorders from the metabolism and nutrition	Very often - hypoglycemia *
Disturbances from the nervous system	Infrequent - peripheral neuropathy ("acute pain neuropathy")
Disturbances on the part of the organ of sight	Infrequent refractive disorders
Disturbances on the part of the organ of sight	Very rarely - diabetic retinopathy
Disturbances from the skin and subcutaneous tissues	Infrequent - lipodystrophy *
General disorders and disorders at the site of administration	Infrequently - reactions in places of administration
	Infrequent edema is infrequent

* See "Description of Selected Adverse Reactions"

Description of individual adverse reactions:

Anaphylactic reactions

Very rare reactions of generalized hypersensitivity have been noted (including generalized skin rash, itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, rapid heart rate, lowering blood pressure, and fainting / unconsciousness that are potentially life-threatening .

Hypoglycaemia

Hypoglycemia is the most common adverse reaction. It can develop if the dose of insulin is too high in relation to the need for insulin. Severe hypoglycemia can lead to loss of consciousness and / or convulsions, temporary or irreversible impairment of brain function or even fatal outcome. Symptoms of hypoglycemia, as a rule, develop suddenly.They may include cold sweats, pale skin, increased fatigue, nervousness or tremor, anxiety, unusual fatigue or weakness, disorientation, decreased concentration, drowsiness, severe hunger, visual impairment, headache, nausea and heart palpitations .

Lipodystrophy

There were reports of infrequent cases of development of lipodystrophy. Lipodystrophy can develop at the site of injection.

Overdose:

A certain dose required for an insulin overdose has not been established, but hypoglycemia can develop gradually if too high doses of insulin are administered relative to the patient's need.

- Light hypoglycemia the patient can eliminate himself by taking glucose or sugar-containing foods. Therefore, patients with diabetes are encouraged to constantly carry with them sugar-containing foods.

- In case of severe hypoglycemia, when the patient is unconscious, 0.5 mg to 1 mg glucagon should be injected intramuscularly or subcutaneously (can be administered by a trained person) or an intravenous solution of dextrose (glucose) (can be administered only by a medical professional).It is also necessary to administer intravenous dextrose in the event that the patient does not regain consciousness 10 to 15 minutes after the administration of glucagon. After restoration of consciousness, the patient is recommended to take a carbohydrate-rich food to prevent the recurrence of hypoglycemia.

Interaction:

There are a number of drugs that affect the need for insulin.

Hypoglycemic action of insulin enhances oral hypoglycemic agents, monoamine oxidase inhibitors, angiotensin-converting enzyme inhibitors, carbonic anhydrase inhibitors, nonselective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, salicylates.

Hypoglycemic action of insulin weakens oral hormonal contraceptives, glucocorticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, growth hormone (somatropin), danazol, clonidine, blockers of slow calcium channels, diazoxide, morphine, phenytoin, nicotine.

Beta-adrenoblockers can mask symptoms of hypoglycemia and make recovery difficult after hypoglycemia.

Octreotide / lanreotide can both increase and decrease the body's need for insulin.

Ethanol can increase or decrease the hypoglycemic effect of insulin.

Incompatibility

Actrapid® NM can be added only to those compounds with which it is known to be compatible. Some drugs (for example, preparations containing thiols or sulfites) when added to insulin solution can cause its degradation.

Special instructions:

Inadequate dose of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia.

Typically, the first symptoms of hyperglycemia appear gradually, within a few hours or days. Symptoms of hyperglycemia are a feeling of thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, and the appearance of an odor of acetone in the exhaled air. Without proper treatment, hyperglycemia in patients with type 1 diabetes mellitus can lead to diabetic ketoacidosis, a condition that is potentially lethal.

Hypoglycaemia

Hypoglycemia can develop if too high a dose of insulin is administered relative to the patient's need.

Skipping meals or unplanned intense exercise can lead to hypoglycemia.

After compensating for carbohydrate metabolism, for example, with intensified insulin therapy, the symptoms typical for them, precursors of hypoglycemia, can change in patients, which patients should be informed about. Common symptoms-precursors can disappear with prolonged course of diabetes.

The transfer of patients to another type of insulin or to the insulin of another manufacturer must be carried out only under medical supervision. If the concentration, producer, type, species (human insulin, human insulin analog) and / or manufacturing method changes, a change in the insulin dose may be required. Patients switching to treatment with Actrapid® HM may require a dose change or an increase in the frequency of injections compared to previously used insulin preparations. If transferring patients to treatment with Actrapid® HM requires a dose adjustment, this can be done already with the administration of the first dose or in the first weeks or months of therapy.

As with other insulin preparations, reactions at the injection site may develop, which is manifested by pain, redness, hives, inflammation, bruising, swelling and itching. Regular injection site changes in the same anatomical area will help reduce symptoms or prevent the development of these reactions. Reactions usually disappear for a few days to several weeks. In rare cases, it may be necessary to cancel the drug Actrapid® HM due to reactions at the injection site. Before the trip associated with the change of time zones, the patient should consult with his attending physician, as changing the time zone means that the patient should take food and inject insulin at another time.

Use of the drug Actrapid® HM for prolonged subcutaneous insulin infusions (PPII) is not permitted because of the risk of precipitation in pump catheters.

The simultaneous use of drugs of the thiazolidinedione group and insulin preparations

Cases of chronic heart failure in the treatment of patients with thiazolidinediones in combination with insulin preparations have been reported, especially if such patients have risk factors for developing chronic heart failure.This fact should be taken into account when appointing patients combination therapy with thiazolidinediones and insulin preparations. When this combination therapy is prescribed, it is necessary to conduct medical examinations of patients for signs and symptoms of chronic heart failure, increase in body weight and the presence of edema. If patients become symptomatic of heart failure, treatment with thiazolidinediones should be stopped.

Precautions for use

For intravenous administration, infusion systems containing the drug Actrapid® HM 100 IU / ml are used at concentrations of 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 concentration of glucose in the blood.

Syringe pens should only be used in conjunction with compatible products, which ensures the safety and effectiveness of their use.

The needles and drug Actrapid® NM in the FlexPen® pen are only for individual use. Do not refill the syringe pen cartridge.

Do not use Actrapid® HM if it has been frozen.

Do not use Actrapid® HM if it has ceased to be clear and colorless.

The drug Actrapid® HM can not be used in insulin pumps for prolonged subcutaneous insulin infusion.

Inform the patient of the need to discard the needle after each injection.

In emergency cases (hospitalization, failure of the insulin delivery device), the drug Actrapid® NM for administration to the patient can be removed from the FlexPen® syringe using an insulin syringe U100.

Instructions for use for patients

Do not use Actrapid® HM:

- In insulin pumps.

- If you are allergic (hypersensitive) to human insulin or any of the components that make up the drug Actrapid® NM.

- If the You begin hypoglycemia (low concentration of glucose in the blood).

- If the protective cap is missing or worn loosely. Each bottle has a protective plastic cap. If the protective cap on the new vial is damaged, return the vial to the pharmacy.

- If the storage conditions were violated drug or it was frozen.

- If insulin has ceased to be transparent and colorless.

Before using Actrapid® HM:

- Checkthose label to make sure, that you are using the right type of insulin.

- Remove the protective cap.

Mode of application

Actrapid® HM is intended for subcutaneous injections. Each time, change the injection site within the anatomical area. This will help reduce the risk of seals and ulcers at the injection site. The best places for injections are: the area of the front abdominal wall, buttocks, front surface of the thigh or shoulder. Insulin will act faster if it is injected into the anterior abdominal wall.

In special cases, Actrapid® HM can be administered intravenously, but such procedures can only be performed by a medical professional.

How to administer Actrapid® HM if only Actrapid® HM is administered or if it is necessary to mix Actrapid® HM with long-acting insulin

- Be sure to use an insulin syringe, on which a scale is plotted, allowing to measure the dose of insulin in units of action.

- Fill the syringe with air in an amount corresponding to the desired dose of insulin.

- Follow the instructions, which was given to you by a doctor or nurse.

- Enter the insulin under the skin. Use the injection technique recommended by your doctor or nurse.

- Hold the needle under the skin at least 6 seconds in order to make sure that the insulin dose is completely introduced.

Effect on the ability to drive transp. cf. and fur:

The ability of patients to concentrate and respond to the reaction may be impaired during hypoglycemia, which can be dangerous in situations where these abilities are particularly necessary (for example, when driving vehicles or working with machines and mechanisms).

Patients should be advised to take measures to prevent the development of hypoglycemia in the management of vehicles.This is especially important for patients with a lack or decline in symptomatic signs of developing hypoglycemia or patients with frequent episodes of hypoglycemia. In these cases, the expediency of driving vehicles and performing such work should be considered.

Form release / dosage:

Solution for injection, 100 IU / ml.

Packaging:

1) For 10 ml of the drug in a bottle of glass 1 of hydrolytic class, sealed with a cork made of bromobutyl rubber / polyisoprene under aluminum rolling and a protective plastic cap. For 1 bottle together with the instruction but application in a cardboard pack.

2) For 3 ml of the drug in the cartridges of glass I hydrolytic class, sealed with disks of brombutyl rubber / polyisoprene on one side and pistons of brombutyl rubber on the other side. The cartridge is sealed in a multi-dose disposable polypropylene syringe pen for multiple injections of FlexPen®. For 5 multi-dose disposable syringe pens along with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature of 2 to 8 °C (in the refrigerator), but not next to the freezer. Do not freeze.

For the opened bottle: do not store in the refrigerator.Store at a temperature of no higher than 25 ° C for 6 weeks.

Store the vial in a cardboard box to protect the light.

For the used or portable as a spare syringe pen with the drug: do not store in the refrigerator. Store at a temperature of no higher than 30 ° C for 6 weeks.

To protect from light, store FlexPen® with the cap on.

Actrapid® NM should be protected from exposure to excessive heat and light.

Keep out of the reach of children.

Shelf life:

30 months.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014272 / 02

Date of registration:20.04.2007 / 01.06.2015

Expiration Date:Unlimited

The owner of the registration certificate:Novo Nordisk A / SNovo Nordisk A / S Denmark

Manufacturer: & nbsp

NOVO NORDISK, A / S Denmark

Representation: & nbspNOVO NORDISK TOVNOVO NORDISK TOVDenmark

Information update date: & nbsp29.06.2017

Illustrated instructions

Instructions

Actrapid® HM (Actrapid® NM)