ORALTEK (MONOALERGEN)

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GENSULIN M30

Composition

active substance: recombinant human insulin (a mixture of 30% soluble and 70% isophane insulin); 1 ml of suspension contains 100 IU of recombinant human insulin (a mixture of 30% soluble insulin and 70% isophane insulin); excipients: m-cresol; phenol; glycerin; protamine sulfate; zinc oxide; sodium dihydrogen phosphate dihydrate; hydrochloric acid (diluted); water for injections.

Pharmaceutical Form

Suspension for injection.

Main Physico-Chemical Properties

A white suspension that, when left to settle, separates into a white sediment and a colorless or almost colorless liquid.

Pharmacotherapeutic Group

Antidiabetic agents. Insulin and analogues. Insulins and analogues of short duration of action in combination with insulins of medium duration of action for injection. Human insulins.

ATC Code A10A D01.

Pharmacological Properties

Pharmacodynamics

Gensulin M30 is a medicinal product of recombinant human insulin (a mixture of 30% soluble insulin and 70% isophane insulin) obtained by genetic engineering using a genetically modified but non-pathogenic strain of E. coli. Insulin is a hormone produced by the cells of the pancreas. Insulin is involved in carbohydrate, protein, and fat metabolism, promoting, among other things, a decrease in blood glucose concentration.

Insulin exhibits several anabolic and anti-catabolic properties depending on the type of tissue. In muscle tissue, insulin enhances the synthesis of glycogen, fatty acids, glycerol, and proteins. This increases the absorption of amino acids and simultaneously reduces the intensity of glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism, and amino acid consumption. A lack of insulin in the body is the cause of diabetes mellitus. Insulin administered by injection acts in the same way as the hormone produced by the body.

Pharmacokinetics

Gensulin M30 starts to act within 30 minutes after administration; the maximum effect is observed between 2 and 8 hours, and the duration of action is up to 24 hours and depends on the dose size. In healthy individuals, up to 5% of insulin is bound to blood proteins. The presence of insulin has been found in cerebrospinal fluid at concentrations that are approximately 25% of those found in serum.

Insulin is metabolized in the liver and kidneys. Small amounts are metabolized in muscles and adipose tissue. In patients with diabetes mellitus, metabolism occurs as in healthy individuals. Insulin is excreted by the kidneys. Trace amounts are excreted in the bile. The half-life of human insulin is approximately 4 minutes. Kidney and liver diseases may delay the excretion of insulin. In elderly individuals, the excretion of insulin occurs more slowly, and the duration of the hypoglycemic action of the medicinal product is prolonged.

Clinical Characteristics

Indications

Treatment of patients with diabetes mellitus who require insulin therapy.

Contraindications

Hypoglycemia. Increased individual sensitivity to the medicinal product Gensulin M30 and any of its components, except in cases where it is used as desensitizing therapy.

Must not be administered intravenously.

Special Precautions

The medicinal product Gensulin M30 must not be used:

• if the cartridge or syringe has been dropped or subjected to external pressure, as this may cause damage and leakage of insulin;
• if it has been stored incorrectly or frozen;
• if the liquid contained in it is not uniformly cloudy;
• a vial or cartridge must not be used if, after mixing, the suspension remains clear or if a white sediment forms at the bottom;
• a medicinal product must not be used if, after mixing, white flakes or white particles remain on the walls of the container, giving the impression of freezing.

Consumption of alcohol may lead to a dangerous decrease in blood sugar levels.

Interactions with Other Medicinal Products and Other Types of Interactions

Patients should inform their doctor about any concomitant treatment being taken with human insulin.

Gensulin M30 must not be mixed with insulins of animal origin or with biosynthetic insulins from other manufacturers. Many medicinal products (including certain antihypertensive and cardiac agents, lipid-lowering agents, medications used to treat pancreatic disorders, certain antidepressants, antiepileptics, salicylates, antibacterial agents, oral contraceptives) may affect the action of insulin and the effectiveness of insulin therapy.

Medicinal products that enhance the action of insulin: beta-blockers, chloroquine, ACE inhibitors, MAO inhibitors (antidepressants), methyldopa, clonidine, pentamidine, salicylates, anabolic steroids, cyclophosphamide, sulfonamides, tetracyclines, quinolone antibiotics, and ethanol.

Medicinal products that reduce the action of insulin: diltiazem, dobutamine, estrogens (including oral contraceptives), phenothiazines, phenytoin, pancreatic hormones, heparins, calcitonin, corticosteroids, antiviral agents used to treat HIV infection, niacin, thiazide diuretics.

The need for insulin may increase when using medicinal products with hyperglycemic activity, such as glucocorticoids, thyroid hormones, and growth hormone, danazol, beta-2 sympathomimetics (e.g., ritodrine, salbutamol, terbutaline), thiazides.

The need for insulin may decrease when using medicinal products with hypoglycemic activity, such as oral hypoglycemic agents, salicylates (e.g., acetylsalicylic acid), certain antidepressants (monoamine oxidase inhibitors), certain ACE inhibitors (captopril, enalapril), non-selective beta-blockers, or alcohol. Somatostatin analogues (octreotide, lanreotide) may both enhance and reduce the need for insulin.

When Gensulin M30 is used in combination with pioglitazone, signs of heart failure may occur, especially in patients with risk factors for heart failure. If this combination is used, the patient's condition should be monitored for signs of heart failure, weight gain, and edema. Pioglitazone treatment should be discontinued if heart symptoms worsen.

Special Features

Decisions regarding changes in the dosing regimen, mixing of insulin medicinal products, and switching from one insulin medicinal product to another should be made by a doctor. Such decisions are made under direct medical supervision and may affect the change in the dose of the medicinal product used. If there is a need to adjust the dose, such adjustments can be made from the first dose or later, over several weeks or months. During insulin therapy, monitoring of blood glucose and urine glucose levels, as well as glycosylated hemoglobin (HbA1c) and fructosamine levels, should be performed. Patients should be taught to self-monitor blood glucose and urine glucose levels using simple tests (e.g., test strips). In different individuals, symptoms of decreased blood sugar levels (hypoglycemia) may appear at different times and may have different intensities. Therefore, patients should be taught to recognize their characteristic symptoms of hypoglycemia. For patients who are changing the type of insulin used (i.e., switching from animal insulin to human insulin), it may be necessary to reduce the insulin dose (due to the possibility of hypoglycemia). In some patients, early symptoms of hypoglycemia after switching to recombinant human insulin may be slightly weaker than those with animal insulins. Early signs of hypoglycemia may also be weaker in patients whose blood glucose levels have been balanced during long-term diabetes, diabetic neuropathy, or when using beta-adrenergic blockers. Both hypoglycemia and hyperglycemia, if left untreated, can lead to loss of consciousness, coma, or a fatal outcome.

The need for insulin may change due to high temperature, severe infection (which may significantly increase the need for insulin), emotional stress, diseases, and disorders of the gastrointestinal tract accompanied by nausea and vomiting, diarrhea, constipation, and malabsorption. The presence of such conditions always requires medical intervention. In such cases, blood glucose and urine glucose levels should be frequently monitored. In patients with renal failure, insulin excretion is reduced, and its duration of action is prolonged.

Patients whose diabetes is associated with pancreatic disorders or coexists with Addison's disease or hypopituitarism are very sensitive to insulin and usually require very small doses of the medicinal product.

In cases of hypopituitarism, pancreatic disorders, adrenal gland disorders, thyroid gland disorders, or liver or kidney failure, the body's need for insulin may change.

During human insulin therapy, antibodies may be produced, although in smaller concentrations than with purified animal insulin.

Insulin resistance may develop during long-term insulin therapy. If insulin resistance occurs, higher doses of insulin should be used.

Incorrect dosing or discontinuation of treatment (especially in patients with insulin-dependent diabetes) may lead to hyperglycemia and potentially life-threatening diabetic ketoacidosis. The need for dose adjustment may arise when changing the intensity of physical activity or usual diet.

Individuals planning long trips across multiple time zones should consult their doctor about adjusting the insulin administration schedule.

Patients must be warned about the need to constantly change the injection site to reduce the risk of developing lipodystrophy and amyloidosis of the skin. There is a potential risk of delayed absorption of insulin and worsening of glycemic control after injections of insulin into areas with these reactions. Changing the injection site to an unaffected area of skin can lead to hypoglycemia. Monitoring of blood glucose levels is recommended after changing the injection site, and dose adjustment of antidiabetic drugs may be considered.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is essentially sodium-free.

Use During Pregnancy or Breastfeeding

Insulin does not cross the placental barrier. For patients who developed diabetes before pregnancy or during pregnancy (gestational diabetes), it is very important to maintain proper carbohydrate metabolism throughout the pregnancy. The need for insulin may decrease during the first trimester of pregnancy and increase during the second and third trimesters. Immediately after childbirth, the need for insulin decreases sharply, which increases the risk of hypoglycemia. Therefore, careful monitoring of blood sugar levels is crucial. There are no restrictions on the use of Gensulin M30 during breastfeeding. However, for women with diabetes who are breastfeeding, there may be a need to adjust the insulin dose and/or diet, as the need for insulin decreases during lactation. The need for insulin returns to the pre-pregnancy level within 6-9 months after childbirth.

Ability to Affect Reaction Speed When Driving or Operating Machinery

The ability to drive vehicles may be impaired due to hypoglycemia, which leads to disturbances in the peripheral nervous system and is accompanied by headache, anxiety, diplopia, impaired associativity, and judgment of distance. In the initial period of insulin therapy, during changes in the medicinal product (in cases of stress or excessive physical exertion, when there are significant fluctuations in blood glucose levels), the ability to drive vehicles and operate machinery may be impaired. It is recommended to monitor blood glucose levels during long trips.

Patients should be informed about the precautions to take before driving a car to avoid hypoglycemic exacerbations, especially if early warning signs of hypoglycemia are absent or not evident, or if hypoglycemic exacerbations occur frequently. Under such circumstances, driving a car is not recommended.

Method of Administration and Dosage

In clinical practice, many treatment regimens with human insulin are known. The choice of a suitable individual regimen for a particular patient should be made by a doctor, taking into account the need for insulin. Based on the established blood glucose level, the doctor determines the necessary dosage and type of insulin preparation for a specific patient. For type 2 diabetes, the average initial dose is 0.2 IU/kg body weight.

Gensulin M30 is administered subcutaneously by injection into the abdominal wall, thigh, shoulder, deltoid, or buttock. The injection sites should always be changed within one area to reduce the risk of developing lipodystrophy and amyloidosis of the skin (see the "Special Features" and "Adverse Reactions" sections). In exceptional cases, it can be administered intramuscularly. Gensulin M30 should be administered 15-30 minutes before a meal. 10-20 minutes before the planned administration, the insulin should be removed from the refrigerator to warm up to room temperature.

Before administration, the vial or cartridge with insulin should be carefully examined. The Gensulin M30 suspension should be uniform and cloudy (uniformly cloudy or milky in appearance).

Special attention should be paid to ensuring that the needle is not inserted into a blood vessel during injection.

Administration using syringes.

For insulin administration, there are special syringes with dose markings. In the absence of syringes and needles for single use, syringes and needles for multiple use can be used, which should be sterilized before each injection. It is recommended to use syringes of the same type and manufacturer. It is always necessary to check if the graduated syringe used is suitable for the dosing of the insulin preparation being administered.

The vial with Gensulin M30 should be rolled between the palms until the suspension becomes uniformly cloudy or milky in appearance.

The order of performing the injection:

• remove the plastic cap without removing the rubber stopper from the vial;
• wipe the rubber stopper with a spirit solution; do not remove the cap from the vial!
• draw air into the syringe in a volume equal to the chosen dose of insulin;
• puncture the rubber stopper and inject air into the vial;
• turn the vial with the syringe upside down;
• make sure the tip of the needle is in the insulin;
• draw the required volume of insulin solution into the syringe;
• remove air bubbles from the syringe by injecting insulin back into the vial;
• re-check the correctness of the drawn dose and withdraw the needle from the vial;
• disinfect the skin at the planned injection site;
• with one hand, stabilize the skin, i.e., pinch it;
• take the syringe in the other hand and hold it like a pencil. Insert the needle into the skin at a right angle (90° angle). Make sure the needle is fully inserted and well positioned in the subcutaneous fat layer, not in deeper skin layers (in thin individuals, the needle should be inserted at a smaller angle);
• to administer the insulin, push the syringe plunger to the end, injecting the dose over at least 5 seconds;
• hold a spirit-soaked cotton swab near the needle and withdraw the needle from the skin. Apply the swab to the injection site for a few seconds. Do not rub the skin at the injection site!
• To avoid tissue damage, it is recommended to change the injection site with each injection. The next injection site should be at least 1-2 cm away from the previous one.

Mixing Gensulin M30 Suspension with Gensulin R Solution

The decision to mix Gensulin M30 with the above-mentioned solution can only be made by a doctor.

Use of Gensulin M30 in Cartridges for Syringe Pens

Gensulin M30 cartridges can be used with reusable syringe pens of the "Ren" type. When filling the syringe pen, attaching the needle, and performing the injection, the manufacturer's instructions for the syringe pen should be followed exactly. If necessary, insulin can be drawn from the cartridge into a standard insulin syringe and used as described above (depending on the insulin concentration and type of preparation).

The Gensulin M30 suspension should be mixed before each injection by shaking it up and down 10 times or rolling it between the palms until the suspension becomes uniformly cloudy or milky in appearance.

Children

There is insufficient experience with the use of the medicinal product in children.

Overdose

In case of insulin overdose, symptoms of hypoglycemia appear, including feelings of hunger, apathy, dizziness, muscle tremors, disorientation, anxiety, rapid heartbeat, increased sweating, nausea, headache, and confusion. In cases of moderate hypoglycemia, it is sufficient to take sweet liquids or foods rich in carbohydrates orally. Rest is recommended. Patients should always carry sugar cubes, glucose, or sweets with them. It is not recommended to eat chocolate, as the fat it contains slows down the absorption of glucose.

Severe hypoglycemia can lead to seizures and loss of consciousness, even fatal outcomes. If the patient is in a coma, glucose should be administered intravenously. After insulin overdose, symptoms of hypokalemia (decreased potassium levels in the blood) may occur, followed by myopathy. In cases of significant hypokalemia, when the patient is no longer able to take food orally, 1 mg of glucagon should be administered intramuscularly and/or a glucose solution intravenously. After regaining consciousness, food should be taken. There may also be a need to continue providing the patient with carbohydrates and to monitor blood glucose levels further, as hypoglycemia may occur after clinical recovery.

Adverse Reactions

In the presence of symptoms of severe hypoglycemia or hyperglycemia with the development of ketoacidosis, immediate medical intervention is necessary. The most common adverse reactions observed during insulin therapy are hypoglycemia (decreased blood glucose levels) and hyperglycemia (elevated blood glucose levels), as well as local manifestations of allergic reactions.

Hypoglycemia. Signs of moderate hypoglycemia: excessive sweating, dizziness, tremors, feelings of hunger, anxiety, tingling in the hands, feet, lips, or tongue, impaired concentration, drowsiness, sleep disturbances, confusion, mydriasis, blurred vision, speech disturbances, depression, irritability. Signs of severe hypoglycemia: disorientation, loss of consciousness, seizures.

Hyperglycemia. In patients with type 1 diabetes, prolonged hyperglycemia leads to ketoacidosis and diabetic coma, which is life-threatening. The first symptoms of acidosis, which appear gradually over several hours or even days, are: drowsiness, facial flushing, thirst, loss of appetite, acetone smell in exhaled air, increased glucose and ketone bodies, tachypnea, and rapid pulse.

Other undesirable effects that occur occasionally with the use of biosynthetic insulins are: insulin lipodystrophy (atrophy or hypertrophy of fatty tissue at the injection site), insulin allergy, insulin resistance.

Local manifestations of allergic reactions are a common undesirable effect (1/100 to <1/10), which include redness of the skin, swelling, or itching, changes at the injection site.

A generalized form of allergy is rare (less than 1/10,000) but is a potentially life-threatening side effect. Cases of generalized allergy include rash on the entire body surface, dyspnea, wheezing, decreased blood pressure, increased heart rate, and sweating.

Disorders of the skin and subcutaneous tissue. Unknown frequency: amyloidosis of the skin; lipodystrophy and amyloidosis of the skin may occur at the injection site and delay local absorption of insulin. Constant rotation of the injection site within a given area may help reduce or prevent these reactions (see the "Special Features" section).

Lipodystrophy may occur at the injection site (frequency from 1/1000 to <1/100).

To avoid tissue damage, it is recommended to change the injection site with each injection.

There have also been reports of:

• edema during insulin therapy, particularly in patients with previously reduced metabolism, which improved with intensive insulin therapy;
• weight gain;
• injection site reactions: skin color changes at the injection site, bleeding, induration at the injection site, swelling at the injection site, injection site nodules, pain, urticaria, and pustules at the injection site;
• itching of individual skin areas and generalized itching;
• dizziness.

Shelf Life

3 years.

The medicinal product must not be used after the expiration date stated on the packaging.

Storage Conditions

After opening the individual packaging, store for 28 days at a temperature not exceeding 25°C. Store at a temperature of 2-8°C in a protected from light place. Do not freeze. Store in a place inaccessible to children.

Incompatibility

As a rule, insulin can be added to substances with which its compatibility has been tested.

Medicinal products added to insulin may cause its destruction, for example, preparations containing thiols or sulfites.

Packaging

10 ml in glass vials, closed with an aluminum cap with a two-layer rubber disk and a plastic cap, No. 1 in a cardboard box; 3 ml in cartridges, No. 5 in a cardboard box.

Release Category

By prescription.

Manufacturer

BIOTON S.A., Poland.

Manufacturer's Location and Address

Legal address: Poland, 02-516, Warsaw, Staroscinska Street, 5.

Production address: Macierzysz, Poznanska Street, 12, 05-850, Ozarow Mazowiecki, Poland.