NovoMix 70 FlexPen - instructions for use, dose, side effects, contraindications

Active substanceInsulin aspart biphasicInsulin aspart biphasic

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NovoMix® 70 FlexPen®

suspension PC

Novo Nordisk A / S Denmark

Dosage form: & nbspsubcutaneous suspension

Composition:

In 1 ml of the drug contains:

active substance: insulin aspart (soluble insulin aspart (70%) and insulin crystals aspart protamine (30%) 100 ED (1 ED corresponds to 0.035 mg (or 6 nmol) of anhydrous insulin aspart);

Excipients: glycerol (glycerol), phenol, m-cresol, zinc chloride, sodium chloride, sodium hydrogen phosphate dihydrate, protamine sulfate, sodium hydroxide, hydrochloric acid, water for injection.

Description:

Homogenous suspension of white color, not containing lumps. Flakes may appear in the sample.

When standing, the suspension stratifies to form a white precipitate and a colorless or almost colorless supernatant.

While stirring the sediment according to the procedure described in the Instruction for Medical Use (see "NovoMix® 70 FlexPan®, Getting Started"), a homogeneous suspension should be formed.

Pharmacotherapeutic group:hypoglycemic agent - a combination of insulin analogues of short and medium duration of action

ATX: & nbsp

A.10.A.D.05 Insulin aspart

Pharmacodynamics:

NovoMix® 70 FlexPen® is a two-phase suspension consisting of soluble insulin aspart (70% of short-acting insulin analog) and insulin crystals of aspart protamine (30% insulin analog of average duration of action). Active substance NovoMix® 70 FlexPen® is insulin aspart, produced by biotechnology of recombinant DNA using a strain Saccharomyces cerevisiae (in the molecular structure of insulin, the amino acid proline in position B28 is replaced with aspartic acid).

Interacts with a specific receptor cytoplasmic outer cell membrane to form insulin-receptor complex stimulates intracellular processes, in m. H. Synthesis of some key enzymes (hexokinase, pyruvate kinase, glycogen and others.). Reduction of blood glucose is due to increased intracellular transport, increased digestion, stimulation of lipogenesis, glycogenogenesis, a decrease in the rate of production of glucose by the liver, etc.

Compared with soluble human insulin, insulin aspart (high-speed analog of human insulin) begins to act more quickly, so it can be administered immediately before meals (0 to 10 minutes before meals). The crystalline phase (30%) consists of insulin aspart protamine (an analog of human insulin of average duration of action), whose action is similar to that of human NPH insulin.

After the subcutaneous administration of NovoMix® 70, the FlexPan® effect develops within 10-20 minutes. The maximum effect is observed in the range from 1 to 4 hours after the injection. The duration of the drug is between 14 and 24 hours. Insulin aspart has the same activity with human insulin in a molar equivalent.

Pharmacokinetics:

In insulin aspart, the substitution of the amino acid proline in position B28 for aspartic acid reduces the tendency of the molecules to form hexamers in the soluble fraction NovoMix® 70 FlexPen®, which is observed in soluble human insulin. Concerning insulin aspart (70%) is absorbed from the subcutaneous fat faster than soluble insulin contained in biphasic human insulin.Insulin aspart protamine (30%), like human NPH insulin, is absorbed longer.

In healthy volunteers, with subcutaneous administration of the drug at a dose of 0.3 U / kg body weight, the average maximum serum insulin concentration was 645 ± 185 pmol / L and was reached 60 minutes after the injection. In patients with type 2 diabetes mellitus, the maximum serum insulin concentration was reached 75 minutes after administration.

In patients with type 1 diabetes, the mean maximum plasma concentration of 721 ± 184 pmol / L was achieved within 60 minutes after subcutaneous administration at a dose of 0.3 U / kg body weight.

In elderly patients, children, as well as patients with impaired liver or kidney function, the pharmacokinetics of NovoMix® 70 FlexPen® was not studied.

Preclinical safety data

In the tests in vitro, which included binding to insulin and receptors IGF-1 and the effect on cell growth, it was shown that the properties of insulin aspart are similar to those of human insulin. In addition, it was found that insulin aspart dissociates with insulin receptors similar to human insulin.In acute (one month) and 12-month toxicity studies, no data were obtained on the presence of clinically significant toxic properties in insulin.

Indications:

Diabetes.

Contraindications:

Hypoglycemia.

Increased individual sensitivity to insulin aspart or any of the components of the drug.

It is not recommended to use in children under 18 years of age, because clinical trials NovoMix® 70 FlexPen® they were not conducted.

Pregnancy and lactation:

The clinical experience of using insulin aspart during pregnancy is very limited.

Studies in animals showed no difference between embryotoxicity and teratogenicity of insulin aspart and human insulin.

In the period of possible pregnancy and throughout its term, it is necessary to carefully monitor the condition of patients suffering from diabetes and monitor blood glucose levels. The need for insulin, as a rule, decreases in the first trimester and gradually rises in the II and III trimesters of pregnancy. Shortly after birth, the need for insulin quickly returns to the level that was before pregnancy.

During the breastfeeding period, NovoMix® 70 FlexPen® can be used without restrictions. The introduction of insulin to a nursing mother does not pose a threat to the child. However, it may be necessary to adjust the dose of NovoMix® 70 FlexPen®.

Dosing and Administration:

NovoMix® 70 FlexPen® is intended for subcutaneous administration. Never introduce NovoMix® 70 FlexPen® intravenously.

The dose of the drug is determined by the doctor individually in each case, based on the level of glucose in the blood. On average, the daily dose of the drug varies from 0.5 to 1.0 U / kg / day (depends on the individual characteristics of the patient and the level of glucose in the blood). In patients with insulin resistance (eg, due to obesity), the daily requirement for insulin can be increased, and in patients with residual endogenous insulin secretion it is lowered.

Patients suffering from type 2 diabetes mellitus, NovoMix 70 can be prescribed both in monotherapy and in combination with metformin in those cases when the blood glucose level is not adequately regulated by one metformin. The recommended starting dose of NovoMix 70 when combined with metformin is 0.2 U / kg / day,and it should be adjusted depending on the individual need for insulin, based on the blood glucose content.

NovoMix 70 should be administered immediately before meals. If necessary, you can enter NovoMix 70 soon after you start eating. The temperature of the insulin should be appropriate at room temperature.

NovoMix® 70 FlexPen® should be administered subcutaneously in the thigh or anterior abdominal wall area. If desired, the drug can be injected into the shoulder or buttock area.

It is necessary to change the injection site within the anatomical area to prevent the development of lipodystrophy.

As with any other insulin preparation, the duration of NovoMix® 70 FlexPene® depends on the dose, site of administration, blood flow intensity, temperature and level of physical activity. Dependence of absorption of NovoMix® 70 FlexPene® from the site of administration has not been studied.

Side effects:

Adverse reactions observed in patients using NovoMix® 70 FlexPen® are mainly dose-dependent and are caused by the pharmacological action of insulin.The most common undesirable phenomenon in the use of insulin is hypoglycemia. Hypoglycemia develops if too high a dose of insulin is administered relative to the body's need for insulin. Pronounced hypoglycemia can lead to loss of consciousness, temporary or irreversible disruption of the brain or death.

When conducting clinical trials, and even after the drug was on sale, the observed frequency of this complication varied depending on the study population and dosing regimens, so it is not possible to indicate the incidence of hypoglycemia when taking NovoMix® 70 FlexPen®. In clinical studies, there was no difference in the incidence of hypoglycemia in admission insulin aspart and preparations of human insulin.

The incidence of side effects associated with NovoMix® 70 FlexPen® (insulin aspart) is presented below. The incidence of side effects was defined as infrequent (> 1 / 1,000, <1/100) and rare (> 1 / 10,000, <1 / 1,000). Individual spontaneous cases are presented as very rare and defined as (<1 / 10,000 - including individual cases).

Immune system disorders

Hives, rashes - rarely.

Anaphylactic reactions are extremely rare.

Symptoms of a generalized hypersensitivity reaction can include: generalized skin rash, itching, sweating, gastrointestinal disorders, angioedema, difficulty breathing, palpitations and decreased blood pressure. Generalized hypersensitivity reactions are potentially life threatening.

Nervous System Disorders

Peripheral neuropathy is extremely rare.

Rapid improvement in glycemic control may be associated with the development of usually reversible acute pain neuropathy.

Ophthalmic disorders

Refractive disorders are rare.

Abnormalities of refraction can develop at the onset of insulin therapy. These symptoms are usually reversible.

Diabetic retinopathy is rare.

Prolonged adequate glycemic control reduces the risk of progression of diabetic retinopathy.

However, an increase in the intensity of insulin therapy with a sharp improvement in glycemic control may be associated with a transient deterioration in the course of diabetic retinopathy.

Lesions of the skin and subcutaneous tissue

Lipodystrophy is rare.

Lipodystrophy can develop at the injection site if it is not possible to change it within the anatomical region.

Local hypersensitivity reactions are rare.

Local hypersensitivity reactions (redness, swelling and itching at the injection site) can be observed with the use of insulin preparations. They are usually transient and disappear when the treatment is continued.

Systemic disorders

Edema is rare.

Edema can develop at the onset of insulin therapy. They are usually transient.

Overdose:

Specific signs of an insulin overdose are absent. However, when taking insulin preparations in doses exceeding the requirements in it, hypoglycemia may develop.

Treatment: slight hypoglycemia, the patient can eliminate himself by taking glucose, sugar or carbohydrate-rich foods inside. Therefore, patients with diabetes are encouraged to always carry sugar, sweets, cookies or sweet fruit juice.

In severe cases, if the patient lost consciousness, intravenously injected 40% glucose solution (dextrose); intramuscularly, subcutaneously - glucagon (0.5-1 mg). After restoration of consciousness the patient is recommended to take food rich in carbohydrates, to prevent the repeated development of hypoglycemia.

Interaction:

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

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

Hypoglycemic action of insulin weakens oral contraceptives, glucocorticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.

Under the influence of reserpine and salicylates, both weakening and enhancement of the action of the drug are possible.

Beta-blockers can mask symptoms of hypoglycemia.

Alcohol can enhance and prolong the hypoglycemic effect of insulin.

Incompatibility

Medicines containing thiols or sulphites, when added to insulin aspart, cause its destruction. NovoMix 70 can not be added to infusion solutions.

Special instructions:

Insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia or diabetic ketoacidosis - conditions that are potentially lethal. 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.

NovoMix® 70 FlexPen® should be used in direct connection with food intake. It should be taken into account the high rate of onset of the effect of the drug in the treatment of patients who have concomitant diseases or who take medications that slow food intake. In the presence of concomitant diseases, especially infectious nature, the need for insulin, as a rule, increases.

Violation of kidney or liver function can lead to a decrease in the need for insulin.

Skipping meals or unplanned physical activity can lead to the development of hypoglycemia.

When changing insulin preparations, it is possible to change the early precursors of hypoglycemia,as well as a decrease in their intensity in comparison with those observed with the use of the previous insulin preparation, which patients should be warned about.

Transfer of the patient to a new type of insulin or an insulin preparation of another manufacturer must be carried out under strict medical supervision. If the concentration, type, producer and species (human insulin, animal insulin, human insulin analog) of insulin preparations and / or manufacturing method changes, a dose change may be required.

Patients switching to NovoMix® 70 FlexPen® treatment may require a dose change compared to the doses of previously used insulin preparations. If it is necessary to adjust the dose, it can be done already at the first administration of the drug or during the first weeks or months of treatment. In addition, a change in the dose of the drug may be required with a change in diet and with increased physical exertion. Physical exercises performed immediately after a meal can increase the risk of developing hypoglycemia. Do not use NovoMix® 70 FlexPen® in insulin pumps.

Instructions for storage, use and disposal

The package contains a sheet with instructions for use and storage. It is necessary to emphasize the importance of mixing the NovoMix® 70 FlexPene® suspension immediately before use. Properly mixed liquid must be uniformly white and cloudy.

NovoMix® 70 FlexPen® is for individual use only. Do not refill NovoMix® 70 FlexPan®. Needles NovoFine S are designed for use with FlexPix.

Instructions for using NovoMix® 70 FlexPen® to be given to a patient

Before using NovoMix® 70 FlexPen®:

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

NovoMix® 70 FlexPan® should not be used:

- In insulin pumps.

- If the FlexPen device has been damaged or broken, or if you dropped it, there is a risk of insulin leakage.

- If it was stored in inadmissible conditions or was frozen.

- If insulin is not uniformly white and cloudy after mixing.

- If white lumps appear in the preparation or if white particles stick to the bottom or walls of the cartridge, giving it the appearance of frozen.

NovoMix® 70 FlexPen® is intended for subcutaneous injections.Never introduce this insulin intravenously and intramuscularly.

Always change the injection site to avoid edema formation. The most suitable places for injection are: abdomen, buttocks, front of the thigh or shoulder. Insulin will act faster when it is introduced into the anterior abdominal wall area.

Instructions for patients on the use of NovoMix® 70 FlexPen®

Please read the following instructions carefully before using NovoMix® 70 FlexPan®.

Introduction

NovoMix® 70 FlexPen® is a unique pen-syringe designed for the administration of insulin. The injected dose of insulin, ranging from 1 to 60 units, can vary in steps of 1 unit. NovoMix® 70 FlexPan® is used with Novoin® S short needles (8 mm or less). Packing of short needles NovoFine is marked S. Marking S has needles with a short tip. As a precaution, always wear a spare system for the introduction of insulin in the event of loss or damage to your FlexPen.

Pen Cap - the cap of the handle

Residual scale - residue scale

Residual scale window - the scale of the balance scale

12 units - 12 units

Rubber membrane - rubber membrane

Insulin cartridge - cartridge with insulin

Dosage indicator window - the dosage indicator window

Dose selector - Dosage selector

Push button - start button

Outer needle cap - outer needle cap

Inner needle cap - inner needle cap

Needle - the needle

Protective tab - protective label

Getting Started

Make sure that NovoMix® 70 FlexPen® contains the necessary tun insulin.

Remove the cap from the syringe pen.

Before each injection:

- Check that there are at least 12 units of insulin in the cartridge to ensure even mixing. If there are less than 12 units left, use the new NovoMix® 70 FlexPan®.

- When using NovoMix® 70 FlexPan® for the first time, it should be rolled between the palms 10 times - it is important that the syringe handle is in a horizontal position (see figure A). Raise the syringe handle up and down 10 times from position 1 to position 2 (see figure AT), so that the glass ball moves from one end of the cartridge to the other. These manipulations must be repeated, at least once more, so that the contents of the cartridge become uniformly white and cloudy. The liquid is easier to mix when the insulin in the cartridge is at room temperature.

- Before each injection, raise the syringe handle up and down from position 1 to position 2 (see figure AT) at least 10 times, so that the contents of the cartridge become evenly white and cloudy. If this is not enough - roll the syringe handle between the palms and lift it again as described above, so that the contents of the cartridge become evenly white and cloudy.

- After mixing, immediately follow these steps:

- Disinfect the rubber membrane with cotton wool.

- Remove the protective sticker from the Novooin S needle.

- Carefully and tightly screw the needle onto NovoMix® 70 FlexPan® (Figure FROM).

- Remove the large outer and inner needle cap (Figure D).

- Do not throw out the large outer needle cap.

Pre-removal of air from the cartridge

Even with the correct use of the syringe pen, a small amount of air can accumulate in front of each injection in the needle and in the cartridge.

To prevent the ingress of air bubbles and the introduction of the correct dose of the drug, follow the further instructions:

- Dial 2 units of the drug (Figure E)

- While holding the NovoMix® 70 FlexPen® vertically with the needle up, tap the cartridge lightly with your fingertip several times, so that the air bubbles move to the top of the cartridge (figure F).

- While holding the NovoMix® 70 FlexPan® with the needle up, press the start button all the way. The dosage selector will return to zero.

- At the end of the needle should appear a drop of insulin. If this does not happen, repeat the procedure, but no more than six times.

If insulin does not come from the needle, this indicates that the pen syringe is faulty and is not subject to further use.

Dose setting

- Make sure that the dose selector is set to "0".

- Dial the number of units needed for injection (figure G).

The dosage can be adjusted by rotating the dose selector in any direction. When rotating the dose selector counter-clockwise, take care not to accidentally press on the start button, in order to avoid the release of insulin. Do not use a residue scale to measure the dose of insulin.

The dose exceeding the number of units remaining in the cartridge can not be set.

Introduction of insulin

- Insert the needle under the skin (Figure H).

Use the injection technique recommended by your doctor.

- To make an injection, press the start button all the way (figure I). Be careful: when you inject insulin, you should only press the start button.

- When pulling out the needle, hold the start button all the way down. After injection, leave the needle under the skin for at least 6 seconds.

This will ensure the introduction of a full dose of insulin.

Removing the needle

- Close the needle with the outer cap and unscrew it from the syringe-pen, (figure J).

- Throw out the needle observing the precautions.

Always use a new needle for each injection.

Remove the needle after each injection. Otherwise, if the temperature drops, it is possible to drain liquid from NovoMix® 70 FlexPan®, which will lead to a change in the concentration of insulin.

Medical personnel, relatives and other caregivers should follow general precautions when removing and discarding needles to avoid the risk of accidental needle sticking.

Throw away the used NovoMix® 70 FlexPen® with the needle disconnected.

Storage and Care

NovoMix® 70 FlexPlex® is designed for efficient and safe use. NovoMix® 70 FlexPan® requires careful handling. Do not damage NovoMix® 70 FlexPan®, as this may result in insulin leakage. The surface of NovoMix® 70 FlexPen® can be cleaned with a cotton swab dipped in alcohol.Do not immerse the handle in alcohol, do not wash or lubricate it. this may damage the mechanism.

Do not refill NovoMix® 70 FlexPan®.

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

The ability of patients to concentrate and respond quickly to hypoglycemia and hyperglycemia, which can be dangerous in situations where these abilities are particularly necessary (for example, when driving or working with machinery 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 feasibility of doing such work.

Form release / dosage:Suspension for subcutaneous administration, 100 U / ml.

Packaging:

3 ml of the drug in a cartridge of hydrolytic class 1 glass, sealed with a rubber disc on one side and sealed in a syringe pen on the other.A glass bead is placed in the cartridge, which facilitates the mixing of the suspension.

1 cartridge is installed in a plastic multi-dose disposable syringe pen for multiple injections.

For 5 multi-dose plastic disposable syringe pens for multiple injections together with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature of 2 to 8 ° C (in the refrigerator). Do not freeze. Protect from light.

For the syringe pen in use:

NovoMix® 70 FlexPan® should be stored at temperatures below 30 ° C for 4 weeks (after this period, residues must be disposed of).

Do not store the used syringe pen in the refrigerator or at temperatures above 30 ° C (if the used pen is still stored in the refrigerator, then before its further use, stir the contents of the syringe pen according to the procedure described in the Instruction for Medical Use ( see "NovoMix® 70 FlexPan®. Getting Started, Using NovoMix® 70 FlexPlex® for the First Time").

To protect from light, the syringe pen should be closed with a cap.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002524/07

Date of registration:31.08.2007

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