Protafan HM Penfill - 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 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 white suspension, which upon separation stratifies, forming a white precipitate and a colorless or almost colorless supernatant. With stirring, the pellet 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® NM is a medium-length human insulin produced by the biotechnology of recombinant DNA using a strain Saccharomyces cerevisiae.

It interacts with a specific receptor of the outer cytoplasmic cell membrane and forms an insulin-receptor complex that stimulates intracellular processes in h.synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase, etc.).

Reduction in blood glucose is due to increased intracellular transport, increased tissue absorption, lipogenesis stimulation, glycogenogenesis, a decrease in the rate of glucose production by the liver and other

The duration of action of insulin preparations is mainly due to the rate of absorption, which depends on several factors (for example, on the dose, method, site of administration and type of diabetes). Therefore, the profile of the action of insulin is subject to significant fluctuations both in different people and in the same person. Its action begins within 1¹/₂hours after administration, and the maximum effect is manifested for 4-12 hours, with a total duration of about 24 hours.

Pharmacokinetics:

Suction

Completeness of absorption and the beginning of the effect of insulin depends on the mode of administration (subcutaneously, intramuscularly), the injection site (abdomen, thigh, buttocks), the dose (volume of insulin administered), the concentration of insulin in the preparation, etc. 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 observed, sometimes only circulating antibodies to insulin are detected.

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 there are several cleavage sites (hydrolysis) in the human insulin molecule, but none of the metabolites formed due to the cleavage is active.

Excretion

The half-life (T_1/2) is determined by the rate of absorption from the subcutaneous tissues. Thus, T_1/2rather, 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 5-10 hours.

Preclinical safety data

During pre-clinical studies that included toxicity studies with repeated dose administration, genotoxicity, carcinogenic potential and toxic effects on the reproductive sphere, no specific human risk was identified.

Indications:

Diabetes.

Contraindications:

Hypoglycemia.

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

Pregnancy and lactation:

Limitations on the use of insulin during pregnancy does not exist, because insulin does not penetrate the placental barrier. Moreover, if you do not carry out diabetes treatment during pregnancy, then there is a danger to the fetus. Therefore, diabetes should be continued during pregnancy.

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 quickly returns to the level,which was noted before pregnancy.

There are also no restrictions for the use of Protafan® NM during lactation. Carrying out insulin therapy for breastfeeding mothers does not pose a danger to the child. However, the mother may need to adjust the dosage regimen of the drug Protafan® NM and / or diet.

Dosing and Administration:

The drug is intended for subcutaneous 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.

In addition, the doctor determines how many injections a day a patient should receive-one or more.

Protafan® HM can be administered either as a monotherapy or in combination with a fast or short-acting insulin.

If intensive insulin therapy is necessary, this suspension can be used as a basal insulin (injection is given in the evening and / or in the morning), in combination with fast or short-acting insulin, the injections of which must be timed to meals.

If patients with diabetes mellitus achieve optimal control of glycemia, then complications of diabetes, they usually appear later. In this regard, we should strive to optimize metabolic control, in particular, by carefully monitoring the level of glucose in the blood.

Protafan® HM 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, a slower absorption is observed than when it is introduced into the anterior abdominal wall area. If the injection is made into a stretched skin fold, then the risk of accidental intramuscular injection of the drug is minimized.

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

Suspensions of insulin under no circumstances can not be administered intravenously.

Correction of dose

With the defeat of the kidneys or liver, the need for insulin decreases.

Side effects:

Adverse reactions observed in patients on the background of therapy with the drug Protafan NM were predominantly dose-dependent and were due to the pharmacological action of insulin.

As with other insulin preparations, the most common side effect is hypoglycemia. It develops in cases when the dose of insulin significantly exceeds the need for it. During clinical trials, as well as during the use of the drug after its release to the consumer market, it was found that the frequency of hypoglycemia varies between different populations of patients and with the use of different dosing regimens, so it is not possible to indicate exact frequencies.

In severe hypoglycemia, loss of consciousness and / or convulsions may occur, temporary or permanent impairment of brain function and even death may occur. Clinical trials have shown that the incidence of hypoglycemia as a whole did not differ in patients receiving human insulin, and in patients receiving insulin aspart.

Below are the values of the incidence of adverse reactions identified in clinical trials, which were generally considered to be related to the use of Protafan® NM.

The frequency was determined as follows: infrequently (≥1 / 1000, <1/100); very rarely (<1/10000), isolated spontaneous cases.

Immune system disorders

Infrequently - hives, rash.

Rarely anaphylactic reactions.

Symptoms of generalized hypersensitivity may include generalized skin rash, itching, sweating, gastrointestinal disorders, angioedema, dyspnea, palpitations, lowering blood pressure, fainting / unconscious.

Generalized hypersensitivity reactions can pose a threat to life.

Disturbances from the nervous system

Rarely peripheral neuropathy.

If the improvement in blood glucose control has been achieved very quickly, a condition called "acute painful neuropathy," which is usually reversible, can develop.

Disturbances on the part of the organ of sight

Rarely refractive disorders.

Anomalies of refraction are usually noted at the initial stage of insulin therapy. As a rule, these symptoms are reversible.

Infrequently diabetic retinopathy.

If the glycemia is adequately controlled for a long time, then the risk of progressing diabetic retinopathy is reduced.However, the intensification of insulin therapy with a sharp improvement in glycemic control may lead to a temporary increase in the severity of diabetic retinopathy.

Disturbances from the skin and subcutaneous tissues

Infrequently - Lipodystrophy.

Lipodystrophy can develop at the site of injections in the event that there is no permanent change of the injection site within one area of the body.

Disorders from the body as a whole, as well as reactions at the site of drug administration

Infrequently - reactions at the site of injection.

On the background of insulin therapy, reactions can occur at the site of the injection (redness of the skin, swelling, itching, soreness, the formation of a hematoma at the site of the injection). However, in most cases, these reactions are transitory and disappear during the continuation of therapy.

Infrequently swelling.

Puffiness is usually noted at the initial stage of insulin therapy. As a rule, this symptom is transient.

Overdose:

A specific dose, when administered which could be talked about an overdose of insulin, is not established, however, in cases where patients are administered too high doses,exceeding their needs, possible development of the state hypoglycemia varying degrees of severity.

- Light hypoglycemia the patient can eliminate himself by taking 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% solution of dextrose (glucose); 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 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, 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-adrenoblockers can mask the symptoms of hypoglycemia and make it difficult to eliminate hypoglycemia.

Octreotide / lanreotide can both reduce and increase the need for insulin.

Alcohol can enhance and prolong hypoglycemic action of insulin.

Incompatibility

In general, insulin can be used only with those compounds with which it is known to be compatible.

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

Special instructions:

With improperly selected doses or with the abolition of therapy, hyperglycemia, especially in patients with type 1 diabetes. The first symptoms of hyperglycemia usually appear gradually, within a few hours or days.Symptoms include nausea, vomiting, severe drowsiness, redness, dry skin, dry mouth, increased urine output, thirst, loss of appetite, and the smell of acetone from the mouth.

If not treated, hyperglycemia in type 1 diabetes can lead to the development of life-threatening diabetic ketoacidosis. In cases of significant improvement in glycemic control, for example, due to intensified insulin therapy, habitual symptoms-precursors of hypoglycemia may also change, which patients should be warned about.

With concomitant diseases, especially with infections and febrile conditions, the need for patients in insulin usually increases.

If a patient is transferred from one type of insulin to another, then early symptoms, precursors of hypoglycemia, may change or become less pronounced than those seen with the introduction of previous insulin.

The transfer of patients to another type of insulin or to the insulin of another manufacturer must be carried out only under medical supervision. With a change in biological activity, a change in the manufacturer, type, species (animal, human,analogue of human insulin) and / or manufacturing method, a change in the dosage regimen may be required.

If dose adjustment is necessary, this can be done already with the administration of the first dose or in the first weeks or months of therapy.

Skipping meals or unplanned heavy physical activity can cause hypoglycemia.

If the patient is to travel through the intersection of time zones, then he should consult a doctor, because he will have to change the time of insulin administration and eating.

Protafan® HM can not be used in insulin pumps for prolonged subcutaneous administration of insulin.

The composition of the drug Protafan ® NM is metarecil, which can cause allergic reactions.

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

Penfill® cartridges are designed and intended for use only in Novo Nordisk insulin delivery systems and NovoFine needles.

In 1 cartridge contains 3 ml, which is equivalent to 300 ME.

If both Protafan® HM Penfill® and other insulin in the Penfill® cartridge are used concurrently,it is necessary to use two separate injection systems for the introduction of insulin, one for each type of insulin.

Protafan® HM Penfill® is for personal use only. Penfill® cartridges are not intended to be refilled.

Before using Protafan® HM Penfill® it is necessary:

- Check the packaging to make sure that the correct type of insulin is selected.

- Always check the cartridge, including the rubber piston. If any damage is found, or if there is a gap between the rubber piston and the white tape marked, this cartridge can not be used. For further instructions, refer to the instructions for using the insulin delivery system.

- Disinfect the rubber membrane with a cotton swab.

The preparation Protafan® HM Penfill® can not be used in the following cases:

- If the cartridge or insulin delivery device is leaking, or if they are damaged or wrinkled, since there is a risk of insulin leakage in this case.

- If the insulin was stored incorrectly, or if it was frozen.

- If, while stirring the contents of the cartridge according to the instructions for use, insulin does not become uniformly white andcloudy.

Injection technique

Instructions for the patient on how to administer insulin

Before installing the cartridge into the Novo Nordisk insulin delivery system, shake the system with the cartridge in between the positions A and B 10 times, as shown in the figure (see Fig.), So that the glass ball inside the cartridge moves from one end of the cartridge to the other not less than 20 times. These manipulations should be repeated until the liquid becomes uniformly white and cloudy. Immediately make an injection.

Before each injection it is necessary to make at least 10 similar movements. These manipulations should be repeated until the liquid becomes uniformly white and cloudy. Immediately make an injection.

Before carrying out the manipulation on mixing it is necessary to make sure that at least 12 units of insulin remain in the cartridge. If less than 12 units remain in the cartridge, you should use a new cartridge.

Instruct patient how to inject insulin

- Insulin is injected under the skin. To do this, apply the method described in "Instructions for the use of systems for the introduction of insulin (syringe-pens)."

- The needle should remain under the skin for at least 6 seconds, which ensures the introduction of the dose completely.

- After each injection, it is necessary to remove the needle from the syringe-pen. Otherwise, the liquid can flow out of the cartridge of the pen-syringe, which will lead to a change in the concentration of the drug.

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 advisability of driving.

Form release / dosage:

Suspension for subcutaneous administration, 100 IU / ml.

Packaging:

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

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

Storage conditions:

Store in the refrigerator at a temperature of 2 to 8 ° C (not too close to the freezer). Do not freeze. Store the cartridge in a cardboard box to protect it from light.

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

The drug should be protected from heat and sunlight.

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 N014271 / 02

Date of registration:24.04.2007

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

Manufacturer: & nbsp

NOVO NORDISK, A / S Denmark