PROTAPHANE NM PENFILL SUSPENSION FOR INJECTION CARTRIDGE 100ME/ML 3 ML

Clinico-pharmacological group

Human Medium insulin

Pharmacology

Protaphane NM - human medium-length insulin, produced by recombinant DNA biotechnology using Saccharomyces cerevisiae strain. It interacts with a specific receptor of the external cytoplasmic cell membrane and forms an insulin-receptor complex that stimulates intracellular processes, including the synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase, etc.). The decrease in glucose in the blood is due to an increase in its intracellular transport, increased absorption of tissues, stimulation of lipogenesis, glycogenogenesis, a decrease in the rate of glucose production by the liver, etc.

The duration of action of insulin preparations is mainly due to the rate of absorption, which depends on several factors (for example, dose, method, site of administration and type of diabetes). Therefore, the profile of insulin action is subject to significant fluctuations, both in different people and in the same person. Does its action begin for 1? h after administration, and the maximum effect is evident within 4-12 h, while the total duration of action is about 24 h.

Pharmacokinetics

Suction

The completeness of absorption and the onset of the insulin effect depends on the method of administration (subcutaneously, in / m), the site of administration (abdomen, thigh, buttocks), the dose (volume of insulin injected), the concentration of insulin in the preparation, etc.maxPlasma insulin is reached within 2–18 h after subcutaneous administration.

Distribution

There is no marked binding to plasma proteins, sometimes only circulating antibodies to insulin are detected.

Metabolism

Human insulin is cleaved by insulin protease or insulin cleaving 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; however, none of the metabolites formed by cleavage is active.

Removal

The half-life (T?) is determined by the rate of absorption from subcutaneous tissue. So T? rather, it is a measure of absorption, rather than the actual measure of insulin elimination from plasma (T? insulin from the bloodstream is only a few minutes). Studies have shown that T? is about 5-10 hours

Preclinical safety data

In the course of preclinical studies, which included toxicity studies with repeated dose administration, genotoxicity studies, carcinogenic potential, and toxic effects on the reproductive sphere, no specific human risk was identified.

Indications for use of the drug

- diabetes.

Dosing regimen

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 ranges from 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 patients with obesity), and lower in patients with residual endogenous insulin production.

In addition, the doctor determines how many injections a patient should receive per day — one or more. Protaphane NM can be administered both as monotherapy and in combination with insulin of fast or short action. If it is necessary to conduct intensive insulin therapy, this suspension can be used as basal insulin (the injection is given in the evening and / or in the morning), in combination with fast or short-acting insulin, the injections of which should be timed to meals.

If patients with diabetes have optimal glycemic control, then the complications of diabetes usually appear later. In this regard, you should strive to optimize metabolic control, in particular, by carefully monitoring the level of glucose in the blood.

Protaphane NM is usually injected subcutaneously in the thigh. If this is convenient, then injections can also be made in the anterior abdominal wall, in the gluteal region, or in the deltoid muscle of the shoulder. With the introduction of the drug in the thigh region, a slower absorption is observed than with the introduction into the anterior abdominal wall.If the injection is made into a skin fold that has been removed, then the risk of accidental i / m administration of the drug is minimized.

It is necessary to change the injection sites within the anatomical region in order to prevent the development of lipodystrophies.

Under no circumstances should insulin suspensions be administered intravenously.

Dose adjustment

With kidney or liver damage, the need for insulin is reduced.

Adverse Effects

Adverse reactions observed in patients during therapy with Protaphane HM 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 where the insulin dose significantly exceeds the need for it. During clinical trials, as well as during the use of the drug after its release on the consumer market, it was found that the frequency of hypoglycemia is different in different patient populations and when using different dosage regimens, therefore, it is not possible to indicate exact frequency values.

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

Below are the frequency of adverse reactions identified in clinical trials, which, according to the general opinion, were regarded as associated with the use of the drug Protaphane HM. The frequency was determined as follows: infrequently (> 1/1000, <1/100); very rarely (<1/10000), isolated spontaneous cases.

Immune system disorders

Infrequently - urticaria, rash.

Very rarely - Anaphylactic reactions.

Symptoms of generalized hypersensitivity may include generalized skin rash, itching, sweating, disorders of the gastrointestinal tract, angioedema, shortness of breath, palpitations, decreased blood pressure, fainting / loss of consciousness.

Generalized hypersensitivity reactions can be life threatening.

Nervous system disorders

Very rarely - peripheral neuropathy.

If an improvement in blood glucose control was achieved very quickly, a condition called “acute painful neuropathy” may develop, which is usually reversible.

Violations by the organ of vision

Very 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 adequate glycemia control is provided for a long time, the risk of progression of diabetic retinopathy is reduced. However, the intensification of insulin therapy with a dramatic improvement in glycemic control can lead to a temporary increase in the severity of diabetic retinopathy.

Violations of the skin and subcutaneous tissues

Infrequently - lipodystrophy.

Lipodystrophy may develop at the injection site in the event that they do not constantly change the injection site within one area of ​​the body.

Violations of the body as a whole, as well as reactions at the site of injection

Infrequently - reactions at the injection site.

During insulin therapy, reactions can occur at the injection site (redness of the skin, swelling, itching, pain, hematoma formation at the injection site). However, in most cases, these reactions are transient and disappear in the process of continuing therapy.

Infrequently - puffiness.

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

Contraindications to the use of the drug

- hypoglycemia;

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

Use of the drug during pregnancy and lactation

Restrictions on the use of insulin during pregnancy does not exist, since insulin does not penetrate the placental barrier. Moreover, if you do not treat diabetes during pregnancy, there is a danger to the fetus. Therefore, the treatment of diabetes must continue during pregnancy.

Both hypoglycemia and hyperglycemia, which can develop in cases of insufficiently well-chosen therapy, increase the risk of fetal malformations and fetal death.Pregnant women with diabetes should be monitored throughout their pregnancy, they need to exercise enhanced control of blood glucose levels; The same recommendations apply to women who are planning a pregnancy.

Insulin requirements usually decrease in the first trimester of pregnancy and gradually increase in the second and third trimesters.

After birth, the need for insulin quickly returns to the level that was noted before pregnancy.

There are also no restrictions on the use of the drug Protaphane HM in the period of lactation. Conducting insulin therapy for nursing mothers is not dangerous for the child. However, the mother may need to adjust the dosage regimen of Protaphane HMi and / or diet.

special instructions

With the wrong dose or with the abolition of therapy may develop hyperglycemia, especially in patients with type 1 diabetes. The first symptoms of hyperglycemia usually appear gradually over several hours or days. Such symptoms include nausea, vomiting, severe sleepiness, reddened, 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, the usual symptoms of precursors of hypoglycemia may also change, which patients should be warned about.

With comorbidities, especially with infections and feverish conditions, patients' need for insulin usually increases.

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

Transfer of patients to another type of insulin or to insulin of another manufacturer should only be carried out under medical supervision. If you change the biological activity, change the manufacturer, type, type (animal, human, analogue of human insulin) and / or method of manufacture, you may need to change the dosage regimen.

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

Skipping meals or unplanned heavy physical exertion can cause hypoglycemia.

If the patient is going to travel across time zones, then he should consult with his doctor, since he will have to change the time for insulin administration and food intake.

Protaphane HM can not be used in insulin pumps for continuous subcutaneous injection of insulin.

The composition of the drug Protaphane HM includes metacresol, which can cause allergic reactions.

Influence on ability to drive and work with mechanisms

The ability of patients to concentrate and the reaction rate may be impaired during hypoglycemia and hyperglycemia, which can be dangerous in situations where these abilities are especially needed (for example, when driving or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia while driving a car and working with mechanisms. This is especially important for patients with the absence 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 driving.

Overdose

The specific dose, with the introduction of which it would be possible to talk about an overdose of insulin, has not been established, however, in cases when patients are administered too high doses that exceed their needs, the state may develophypoglycemia varying degrees of severity:

- The patient can eliminate a slight hypoglycemia himself by taking in sugar or carbohydrate-rich foods. Therefore, patients with diabetes are advised to constantly carry with them sugar, sweets, cookies or sweet fruit juice.

- in severe cases, when the patient loses consciousness, a 40% dextrose (glucose) solution is administered in / in; in / m, subcutaneously - glucagon (0.5 -1 mg). After regaining consciousness, the patient is recommended to take carbohydrate-rich food to prevent the recurrence of hypoglycemia.

Drug interaction

There are a number of drugs that affect the need for insulin.Hypoglycemic effect containing ethanol.

The hypoglycemic effect 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 strengthening the effect of the drug are possible.

Beta-blockers can mask the symptoms of hypoglycemia and inhibit the elimination of hypoglycemia.

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

Alcohol can enhance and prolong the hypoglycemic effect of insulin.

Incompatibility

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

Insulin suspensions cannot be added to infusion solutions.

Pharmacy sales terms

The drug is available on prescription.

Terms and conditions of storage

Shelf life - 30 months. Do not use after expiration date.

The drug should be stored in a refrigerator at a temperature of from 2 ° C to 8 ° C (not too close to the freezer). Do not freeze. Store the cartridge in a carton to protect it from light.

For opened cartridges: Store at a temperature not exceeding 30 ° C for 6 weeks. Do not store in the refrigerator.

The drug should be protected from heat and sunlight.

Keep out of the reach of children.