Actrapid HM Penfill - instructions for use, dose, side 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 pH adjustment), water for injection up to 1.0 ml.

1 cartridge 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.

Reduction of blood glucose level occurs due to increase of its intracellular transport after insulin binding with insulin receptors of muscle and adipose tissue and 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® HM in intensive care patients who underwent serious surgical interventions (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_max) of insulin in plasma is achieved within 1.5-2.5 hours after subcutaneous administration.

Distribution

Expressed binding to plasma proteins is not observed, 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_1/2is 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

In preclinical studies, including safety pharmacology studies, toxicity studies with repeated dose administration, genotoxicity studies, carcinogenic potential and reproductive toxicity scope, specific risks have been identified for the individual.

Indications:

Diabetes.

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:

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

As hypoglycemia and hyperglycemia, which can develop in cases not adequately chosen therapy, increase the risk of fetal malformations and fetal death. Pregnant women with diabetes during pregnancy should be supervised, they need to exercise greater control of blood glucose levels; 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.

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.

Actrapid® HM is a short-acting insulin and can be used in combination with long-acting insulins.

Actrapid® HM is usually administered subcutaneously, into the area 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 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.

Actrapid® HM can also be administered intravenously and only a medical professional can perform such procedures.

Intravenous administration of the drug Actrapid® HM Penfill® From the cartridge 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 doctor.

Actrapid® NM Penfill® is designed for use with injection systems for the introduction of Novo Nordisk insulin and NovoFine needles® or NovoTvist®.

Detailed recommendations for the use and administration of the drug should be observed (see Instructions for the Use of Actrapid® NM Penfill®, which must be given patient ").

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 undesirable phenomenon in the use of insulin is hypoglycemia. During 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 and the control of glycemia (see "Description of Selected 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.

- mild hypoglycaemia 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.

When adding the drug Actrapid® HM to infusion solutions, the amount of insulin absorbed by the infusion system is unpredictable, so the use of Actrapid® NM in PPII is not permitted.

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 such combination therapy is prescribed, it is necessary to conduct medical examinations of patients foridentify their signs and symptoms of chronic heart failure, increase body weight and the presence of edema. When worsening in patients with cardiac symptoms insufficiency, treatment thiazolidinediones should be discontinued.

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 injection, 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.

Cartridges should be used in combination with only compatible products, which ensures the safety and efficiency of their use.

The drug Actrapid® HM Penfill® and needles are for individual use only. Do not refill the cartridge.

Do not use insulin preparations if they have been frozen.

Do not use insulin if it has ceased to be clear and colorless.

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) Actrapid® HM for administration to the patient can be removed from the cartridge using an insulin syringe U100.

Instructions for the use of Actrapid® HM Penfill®, which must be given to the patient

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 you have hypoglycemia (low blood sugar).

- If the cartridge or insertion device with the cartridge installed is dropped, or the cartridge is damaged or crushed.

- If the storage conditions of the preparation have been violated, or it has been frozen.

- If insulin has ceased to be transparent and colorless.

Before using Actrapid® HM:

- Check the label to make sure you are using the right type of insulin.

- Always check the cartridge, including the rubber piston. Do not use the cartridge if it has visible damage, or if there is a gap between the piston and the white strip on the cartridge. Return the cartridge to the pharmacy. For further instructions, refer to the instructions for using the insulin delivery system.

- Always use a new needle for each injection to prevent infection.

- Actrapid® HM Penfill® and needles are for personal use only.

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: anterior abdominal wall, buttocks, anterior thigh or shoulder. Insulin will act faster if it is injected into the anterior abdominal wall.

How to inject insulin

- Insulin should be injected under the skin. Use the injection technique recommended by your doctor or nurse, follow the instructions for administering insulin described in the manual for the insulin delivery device.

- Hold the needle under the skin for at least 6 seconds. Hold the start button down until the needle is removed from under the skin. This will ensure the introduction of a full dose of insulin and prevent the ingress of blood into the needle or into the cartridge with insulin.

- Always remove and discard the needle after each injection; Never store Actrapid® HM Penfill® with attached needle. Otherwise, it is possible to leak the liquid from the cartridge, which can lead to an incorrect dosage of insulin.

Do not refill Actrapid® HM Penfill® again.

Penfill® cartridges are designed for use with Novo Nordisk insulin injection systems and NovoFine® or NovoTvist® needles.

If both Actrapid® HM Penfill® and other insulin in the Penfill® cartridge are used simultaneously for treatment, two separate insulin delivery systems, one for each type of insulin, should be used.

As a precaution, always carry a spare insulin delivery system in case you lose or damage your Actrapid® HM Penfill®.

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 decrease in the severity of symptoms-precursors of developing hypoglycemia or suffering from 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:

3 ml of the drug in the cartridges of glass 1 of the hydrolytic class, sealed with lids with bromobutyl rubber / polysoprene discs on one side and pistons of bromobutyl rubber on the other side.

For 5 cartridges in a blister pack together with instructions for use in a cardboard box.

Storage conditions:

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

Store the cartridges in a cardboard box to protect them from light.

For opened cartridges: do not store in the refrigerator. Store at a temperature of no higher than 30 ° C for 6 weeks.

Actrapid® HM Penfill® should be protected from excessive heat and light.

Keep out of the reach of children.

Shelf life:

30 months.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014274 / 02

Date of registration:20.04.2007 / 19.12.2016

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: & nbsp28.06.2017

Illustrated instructions

Instructions

Actrapid® HM Penfill® (Actrapid® NM Penfill®)