Protafan HM - instructions for use, dose, side effects, contraindications

Excipients: zinc 18 mcg (in the form of zinc chloride), glycerol (glycerol) 16 mg, metacresol 1.5 mg, phenol 0.65 mg, sodium hydrogen phosphate dihydrate 2.4 mg, protamine sulfate about 0.35 mg, sodium hydroxide about 0, 4 mg and / or hydrochloric acid of about 1.7 mg (for pH adjustment), 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 white suspension, which upon separation stratifies, forming a white precipitate and a colorless or almost colorless supernatant. When the preparation is stirred according to the procedure described in the instructions for medical use, the precipitate should be resuspended.

Pharmacotherapeutic group:hypoglycemic agent - medium-duration insulin

ATX: & nbsp

A.10.A.C Insulins and their analogues of average duration of action

Pharmacodynamics:

Protafan® HM - a medium-long human insulin preparation produced by the biotechnology method of recombinant DNA using a strain Saccharomyces cerevisiae.

Reducing the concentration of glucose in the blood is due to an increase in its intracellular transport after the binding of insulin with insulin receptors of muscle and fattissue and a simultaneous decrease in the rate of glucose production by the liver.

The effect of the drug begins within 1¹/₂ hours after administration, the maximum effect is evident within 4-12 hours, with a total duration of about 24 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 2-18 hours after subcutaneous injection.

Distribution

Expressed binding to plasma proteins is not noted, except for circulating antibodies to insulin (if any).

Metabolism

Human insulin is cleaved under the action of insulin protease or insulin-degrading enzymes, and possibly also under the action of protein disulfide isomerase. It is assumed that in the human insulin molecule there are several cleavage sites (hydrolysis); however, 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 5-10 hours.

Preclinical 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 mellitus, which needs insulin therapy.

Contraindications:

Hypoglycemia.

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

Pregnancy and lactation:

Pregnancy

Limitations on the use of insulin during pregnancy does not exist, 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 throughout the 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 Protafan® HM during 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 Protafan® NM and / or the diet.

Dosing and Administration:

The drug is intended for subcutaneous administration.

Suspensions of insulin can not be administered intravenously.

The drug Protafan® HM can be used both in monotherapy and in combination with fast or short-acting insulin.

The dose of the drug is selected individually, taking into account the needs of the patient. Usually insulin requirements are 0.3 to 1 IU / kg / day. The daily insulin requirement may be higher in patients with insulin resistance (for example, during puberty, as well as in obese patients) and lower in patients with insulin residual endogenous insulin production.

The drug Protafan® NM is usually administered subcutaneously, into the thigh area. If it is convenient, the injections can also be made in the anterior abdominal wall, in the gluteal region or in the deltoid muscle region of the shoulder. When the drug is injected into the thigh region, slower absorption is noted than when it is 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 prevent the development of lipodystrophy.

The preparation of Protafan® 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.

The FlexPen® pen is a pre-filled syringe pen designed for use with NovoFine® disposable needles or Hovto-twist® length up to 8 mm. Syringe-handle FlexPhen^® allows you to enter a dose of insulin in the range from 1 to 60 units in increments of 1 unit. Follow the detailed recommendations for the use and administration of the drug (see "Protafan® NM solution for injection in vials. Instructions for use for patients " or "Protafan® NM injection for injection into FlexPen® syringes. Instructions for 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 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 dosing regimen and the control of glycemia (see Table 1). "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 the control of carbohydrate metabolism can lead to a temporary deterioration in the state of diabetic retinopathy,at the same time, 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 allocated to the groups according to the frequency of development according to MedDRA 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	Very rarely - peripheral neuropathy ("acute pain neuropathy")
Disturbances on the part of the organ of sight	Very rarely - violation of refraction
Disturbances on the part of the organ of sight	Infrequently - diabetic retinopathy
Disturbances from the skin and subcutaneous tissues	Infrequent - lipodystrophy *
General disorders and disorders at the site of administration	Infrequently - reactions at the site of administration
	Infrequent edema is infrequent

*Cm. "Description of individual adverse reactions"

Description of individual adverse reactions

Anaphylactic reactions

Very rare reactions of generalized hypersensitivity were noted, at including generalized skin rash, itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, heart palpitations, lowering blood pressure, and fainting / unconsciousness, which are potentially life-threatening.

Hypoglycaemia

Hypoglycemia is the most common side effect. 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.

- Easy patient hypoglycemia can eliminate itself. taking in 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 introduce intravenous dextrose in the case if the patient does not regain consciousness 10-15 minutes after the introduction 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, somatropin, danazol, clonidine, blockers of slow calcium channels, diazoxide, morphine, phenytoin, nicotine.

Beta-blockers can mask symptoms of hypoglycemia and slow recovery after hypoglycemia.

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

Alcohol can increase or decrease the hypoglycemic effect of insulin.

Incompatibility

Suspensions of insulin can not be added to solutions for infusion.

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. Carrying appropriate treatment for 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 in relation 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 Protafan® NM may require a dose change or an increase in the frequency of injections compared to previously used insulin preparations. If transfer of patients for treatment with the drug Protafan® HM requires dose adjustment, this can be done already with the introduction of the first dose or in the first weeks or months of therapy.

As with other insulin preparations, reactions can occur at the site of administration, which is manifested by pain, redness, hives, inflammation, bruising, swelling and itching. Regular injection site changes in one and 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 Prothafan® NM because of reactions at the site of administration.

Before a 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 must take food and inject insulin at another time.

Suspensions of insulin can not be used in insulin pumps.

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. In the appointment of such combination therapy, it is necessary to conduct medical examinations of patients to identify signs and symptoms of chronic heart failure, increase in body weight and the presence of peripheral edema.If the symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

Precautions for use

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

The preparation Protafan® NM in the Flexple® syringe pen and needles is for individual use only. He it is possible to refill the syringe-pen cartridge.

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

Before the first use, remove Protafan® NM from the refrigerator and allow it to reach room temperature to facilitate mixing of the suspension.

Insulin suspension can not be used, it sat down after mixing does not become uniformly white and cloudy.

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

Instructions for use for patients

Do not use Protafan® HM:

- In insulin pumps.

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

- If you have hypoglycemia (low blood sugar concentration).

- If the protective cap is missing or is loose. 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 of the drug have been violated or it has been frozen.

- If the insulin does not become uniformly white and cloudy after mixing.

Before using Protafan® HM:

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

- Remove the protective cap.

How to apply the drug Protafan® NM

The drug Protafan® NM is intended for subcutaneous administration. Never administer insulin intravenously or intramuscularly.

Always change the injection site within the anatomical area to reduce the risk of seals and ulceration at the injection site. The best places for injections are: the buttock area, the front surface of the thigh or shoulder.

How to administer Protafan® HM if only Protafan® HM is administered or if it is necessary to mix Protafan® HM with short-acting insulin:

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

- Draw in the syringe air in the amount corresponding to the required dose of insulin.

- Follow the instructions given to you by the doctor or nurse.

- Directly before the dose set, roll the bottle between the palms until the insulin becomes evenly white and cloudy. Resuspension is facilitated if the drug has room temperature.

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

- Hold the needle under the skin for at least 6 seconds to ensure that the insulin dose is completely injected.

Protafan® NM suspension for subcutaneous injection in FlexPen® syringes

Instructions for use for patients

Read this manual carefully before using Protafan® HM in the FlexPen® syringe pen.

The FlexPen® pen is a pre-filled insulin pen with a dispenser. You can choose a dose from 1 to 60 units in steps of 1 unit. The FlexPen® pen is designed for use with NovoFine or NovoTvist® disposable needles up to 8 mm long.As a safety precaution, always carry a spare insulin delivery system in case you lose or injure your FlexPen® syringe with Prothafan® NM.

The FlexPen® syringe with Prothafan® NM

See Fig. 1 and Fig. 2.

Storage and Care

The FlexPen® syringe pen is designed for efficient and safe use and requires careful handling. In the event of a fall or strong mechanical impact, it is possible to damage the syringe handle and leakage of insulin.

From the outside, the FlexPen® syringe can be cleaned with a cotton swab. Do not wash, immerse in liquid and do not lubricate the syringe-pen, because this may damage the mechanism. Do not refill the FlexPen® syringe.

Preparation of the FlexPen® syringe with Prothafan® HM for use

Check the label to make sure that the FlexPen® pen and Protafan® HM contain the type of insulin you need. Mix insulin before the first injection using a new FlexPen® syringe.

To facilitate mixing, allow the product to warm to room temperature. Remove the cap from the syringe handle (see Figure A).

Raise and lower the syringe handle up and down 20 times, as shown in the figure (see Figure B), so that the glass ball moves from one end of the cartridge to the other. Repeat these manipulations until the contents of the cartridge become uniformly white and cloudy.

Before each next injection mix the contents by raising and lowering the syringe handle up and down at least 10 times until the contents of the cartridge become uniformly white and cloudy.

After mixing, immediately inject.

- Always ensure that at least 12 units of insulin remain in the cartridge to ensure even mixing. If there are less than 12 units left, use a new FlexPen® syringe with Protafan® HM.

Attaching the needle

FROM

Remove the protective sticker from the disposable needle.

Carefully and tightly screw the needle onto the FlexPen® syringe pen (see Figure C).

Remove the outer cap of the needle, but do not throw it away (see Figure D).

Remove and discard the inner needle cap (see Figure E).

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

- Be careful not to bend or damage the needle before use.

- To avoid accidental injections, never put the inner cap back on the needle.

Insulin intake check

In the process of using the syringe pen, a small amount of air can accumulate in the cartridge before each injection. To prevent the ingress of air bubbles and ensure the introduction of the correct dose of the drug.

Enter 2 units of the drug by turning the dose selector (see Figure F).

While holding the FlexPen® needle with the needle up, tap the cartridge lightly with the tip of the finger several times, so that the air bubbles move to the top of the cartridge (see Figure G).

Hold the needle with the needle up, press the start button all the way. The DotA selector will return to zero.

At the end of the needle should appear a drop of insulin. If this does not happen, replace the needle and repeat the procedure, but no more than 6 times.

If a drop of insulin has not appeared, this means that the pen syringe is faulty and can not be used (see Figure H).

Dose setting

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

Rotate the dose selector to set the number of units needed for injection. The dose can be adjusted by rotating the dose selector in any direction until the correct dose is set against the dose indicator.To avoid the release of insulin dose, use caution when rotating the dose selector so that you do not accidentally press the start button.

It is not possible to set a dose that exceeds the number of units remaining in the cartridge (see Figure I).

- You can not use an insulin residue scale to measure the dose of insulin.

Introduction of insulin

Insert the needle under the skin. Use the injection technique recommended by your doctor.

To do the injection, press the start button all the way until "0" appears opposite the dose indicator. Be careful: when you inject the drug, you should only press the start button.

When the dose selector is turned, the drug will not be injected (see Figure J).

When removing the needle from under the skin, 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 (see Figure K).

Point the needle into the outer cap of the needle without touching the cap. When the needle completely enters, insert the cap and unscrew the needle.

Throw out the needle, observing the precautionary measures, and close the syringe handle with a cap (see Figure L).

- Remove the needle after each injection and never store the FlexPen® syringe withattached needle. Otherwise, it is possible to drain liquid from the syringe handle, which can lead to incorrect dosage.

- Persons caring for the patient should handle the used needles with extreme care to avoid accidental injections.

- Dispose of the used Flexple® syringe with the needle disconnected.

- The FlexPen® syringe with Protafan® HM and needles is for personal use only, and can not be passed on to others.

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:

Suspension for subcutaneous administration, 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. 1 bottle with instructions for use in a cardboard box.

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. A glass bead is placed in the cartridge to facilitate resuspension. The cartridge is sealed in a multi-dose disposable polypropylene syringe pen for multiple injections of FlexPen®. 5 multi-dose disposable syringes 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.

Protafan® 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014722 / 01

Date of registration:20.04.2007

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

Manufacturer: & nbsp

NOVO NORDISK, A / S Denmark

NOVO NORDISK PRODUCTION, S.A.S. France