Hensulin r

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GENSULIN P (GENSULINR)

Composition:

Active substance: recombinant human insulin 100 IU;

1 ml of solution contains recombinant human insulin 100 IU;

Excipients: m-cresol, glycerin, hydrochloric acid (diluted), sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Antidiabetic agents. Insulins and analogues. Short-acting injectable insulins. Human insulins.

ATC code A10A B01.

Pharmacological properties.

Pharmacodynamics.

Gensulin R is a medicinal product of recombinant human insulin obtained by genetic engineering using a genetically modified, but non-pathogenic strain of E. coli. Insulin is a hormone produced by the pancreatic beta cells. Insulin participates in the metabolism of carbohydrates, proteins, and fats, particularly promoting a reduction in blood glucose concentration. Insulin exhibits several anabolic and anti-catabolic effects depending on the tissue type. In muscle tissue, insulin enhances the synthesis of glycogen, fatty acids, glycerol, and proteins. This increases amino acid uptake and simultaneously reduces the rate of glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism, and amino acid utilization. Insulin deficiency in the body is the cause of diabetes mellitus. Injected insulin acts the same way as the hormone naturally produced by the body.

Pharmacokinetics.

Gensulin R begins to act within 30 minutes after administration; peak effect occurs between 1 and 3 hours, and duration of action lasts up to 8 hours, depending on the dose administered. In healthy individuals, up to 5% of insulin is bound to plasma proteins. Insulin has been detected in cerebrospinal fluid at concentrations approximately 25% of those found in blood serum.

Insulin is metabolized in the liver and kidneys. Small amounts are also metabolized in muscle and adipose tissue. In patients with diabetes mellitus, metabolism proceeds similarly as in healthy individuals. Insulin is excreted by the kidneys. Trace amounts are excreted in bile. The elimination half-life of human insulin is approximately 4 minutes. Renal and hepatic impairment may delay insulin elimination. In elderly individuals, insulin elimination is slower and the duration of hypoglycemic action is prolonged.

Clinical characteristics.

Indications.

Treatment of patients with diabetes mellitus requiring insulin therapy.

Contraindications.

Hypoglycemia. Increased individual sensitivity to the medicinal product Gensulin R and any of its components, except in cases of its use as desensitizing therapy.

Special precautions.

Do not use the medicinal product Gensulin R:

• if the cartridge or pen has been dropped or subjected to external pressure, as this may damage the device and cause insulin leakage;
• if it has been stored improperly or has been frozen;
• if the liquid contained in it is not clear and colorless.

Alcohol consumption may lead to dangerous reduction in blood glucose levels.

Interaction with other medicinal products and other types of interactions

Inform your doctor about any concomitant therapy being administered together with human insulin.

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

Medicinal products and substances that enhance insulin action: β-adrenergic blockers, chloroquine, angiotensin-converting enzyme inhibitors, MAO inhibitors (antidepressants), methyldopa, clonidine, pentamidine, salicylates, anabolic steroids, cyclophosphamide, sulfonamides, tetracyclines, quinolone antibiotics, and ethanol.

Medicinal products that reduce insulin action: diltiazem, dobutamine, estrogens (including oral contraceptives), phenothiazines, phenytoin, pancreatic hormones, heparins, calcitonin, corticosteroids, antiviral drugs used in HIV infection treatment, niacin, thiazide diuretics.

Insulin requirement may increase when using drugs with hyperglycemic activity, such as glucocorticoids, thyroid hormones and growth hormone, danazol, β2-sympathomimetics (e.g., ritodrine, salbutamol, terbutaline), thiazides.

Insulin requirement may decrease when using drugs with hypoglycemic activity, such as oral hypoglycemic agents, salicylates (e.g., acetylsalicylic acid), certain antidepressants (monoamine oxidase inhibitors), certain angiotensin-converting enzyme inhibitors (captopril, enalapril), non-selective β-blockers, or alcohol. Somatostatin analogs (octreotide, lanreotide) may either increase or decrease insulin requirement.

When Gensulin R is used concomitantly with pioglitazone, manifestations of heart failure may occur, especially in patients with risk factors for heart failure. When using this combination, patients should be monitored for symptoms of heart failure, weight gain, and development of edema. Pioglitazone treatment should be discontinued if cardiac symptoms worsen.

Special precautions for use.

The decision regarding changes in insulin dosage regimen, mixing of insulin products, or switching from one insulin product to another must be made solely by a physician. Such decisions must be made under direct medical supervision and may affect the dose of insulin required. If dose adjustments are needed, they may be initiated with the first dose or later over several weeks or months. During insulin therapy, monitoring of blood serum glucose and urine glucose levels, as well as glycated hemoglobin (HbA1c) and fructosamine concentrations, is required. Patients should be trained to independently monitor blood and urine glucose levels using simple tests (e.g., test strips). Hypoglycemic symptoms (low blood sugar) may appear at different times and with varying intensity in different individuals. Therefore, patients should be educated to recognize their individual hypoglycemic symptoms. For patients switching from animal-sourced insulin to human insulin, a reduction in insulin dose may be necessary (due to the risk of hypoglycemia). In some patients, early symptoms of hypoglycemia after switching to recombinant human insulin may be milder compared to those experienced with animal-sourced insulins. Early signs of hypoglycemia may also be less pronounced in patients whose blood glucose has been well-controlled over a long period, in patients with diabetic neuropathy, or in those concurrently using β-adrenergic blocking agents. Both hypoglycemia and hyperglycemia, if left untreated, may lead to loss of consciousness, coma, or death.

Insulin requirements may change due to high fever, severe infection (which may significantly increase insulin needs), emotional stress, illnesses, or gastrointestinal disorders associated with nausea and vomiting, diarrhea, constipation, or impaired absorption. The presence of such conditions always requires medical intervention. In these cases, blood and urine glucose levels should be monitored frequently. In renal insufficiency, insulin excretion is reduced and its duration of action prolonged.

Patients whose diabetes is associated with pancreatic disorders or who have Addison’s disease or hypopituitarism are highly sensitive to insulin and typically require very low doses of the medication.

Insulin requirements may change in patients with disorders of the pituitary gland, pancreas, adrenal glands, thyroid gland, or in those with hepatic or renal insufficiency.

Antibody production may occur during treatment with human insulin, although at lower concentrations compared to purified animal-sourced insulin.

With prolonged insulin therapy, insulin resistance may develop. If insulin resistance occurs, higher insulin doses may be required.

Incorrect dosing or discontinuation of treatment (especially in patients with insulin-dependent diabetes) may lead to hyperglycemia and potentially fatal diabetic ketoacidosis. Dose adjustments may be necessary when there are changes in the level of physical activity or usual dietary patterns.

Patients planning long-distance travel across multiple time zones should consult their physician regarding insulin schedule adjustments.

Patients should be advised to rotate injection sites regularly to reduce the risk of lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and impaired glycemic control following insulin injections into areas affected by these reactions. Reports indicate that changing the injection site to an unaffected area of skin may lead to hypoglycemia. It is recommended to monitor blood glucose levels after changing the injection site, and dose adjustment of antidiabetic medications may need to be considered.

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically 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), maintaining adequate carbohydrate metabolism control throughout pregnancy is critically important. Insulin requirements may decrease during the first trimester and increase during the second and third trimesters. Insulin requirements drop sharply immediately after delivery, increasing the risk of hypoglycemia. Therefore, careful blood glucose monitoring is essential. There are no restrictions on the use of Gensulin R during breastfeeding. However, breastfeeding women may require dose and dietary adjustments, as insulin requirements during lactation fall below pre-pregnancy levels. Insulin requirements return to pre-pregnancy levels within 6–9 months after delivery.

Ability to influence the speed of reactions when driving or operating machinery.

The ability to drive or operate machinery may be impaired due to hypoglycemia, which can cause peripheral nervous system disturbances and is accompanied by headache, anxiety, diplopia, and impaired association and distance perception. During the initial period of insulin therapy, when changing insulin products, or during stress or excessive physical exertion—especially when significant fluctuations in blood glucose levels occur—the ability to drive vehicles or operate moving machinery may be compromised. It is recommended to monitor blood glucose levels during prolonged travel.

Administration and Dosage

In clinical practice, numerous human insulin treatment regimens are known. The appropriate individual regimen for a specific patient should be selected by a physician based on the patient's insulin requirements. The physician determines the required dosage and type of insulin preparation according to the patient's blood glucose concentration. In type 2 diabetes, the average initial dose is 0.2 IU/kg body weight.

Gensulin R is intended for subcutaneous and also intravenous injections. Gensulin R is administered subcutaneously by injection into the abdominal wall, thigh, shoulder, deltoid, or gluteal area. Injection sites should always be rotated within one area to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections "Special Instructions" and "Adverse Reactions"). In exceptional cases, it may be administered intramuscularly. Gensulin R should be administered 15–30 minutes before a meal. Approximately 10–20 minutes before the planned injection, the insulin should be removed from the refrigerator to allow it to warm to room temperature.

Before administration, carefully inspect the insulin vial or cartridge. Gensulin R solution should be colorless and clear, with a watery appearance and consistency. The product must not be used if the solution is cloudy, appears viscous, or is discolored. Special care should be taken to ensure that the insulin is not injected directly into a blood vessel.

Administration using syringes

Special syringes marked with insulin dosage units are available for insulin administration. In the absence of disposable syringes and needles, reusable syringes and needles may be used, provided they are sterilized before each injection. It is recommended to use syringes of the same type and manufacturer. Always verify that the syringe used is calibrated appropriately according to the insulin preparation's concentration.

Injection procedure:

• Remove the plastic cap without removing the actual vial cap;
• Wipe the vial stopper with an alcohol swab; do not remove the cap from the vial!
• Draw into the syringe an amount of air equal to the intended insulin dose;
• Pierce the rubber stopper and inject the air into the vial;
• Invert the vial and syringe so that the vial is upside down;
• Ensure the tip of the needle is immersed in the insulin solution;
• Draw the required volume of insulin solution into the syringe;
• Remove air bubbles from the syringe by expelling insulin back into the vial;
• Recheck the correct dose and withdraw the needle from the vial;
• Disinfect the skin at the injection site;
• With one hand, stabilize the skin by pinching it into a fold;
• Hold the syringe in the other hand like a pencil. Insert the needle into the skin at a 90° angle. Ensure the needle is fully inserted and properly positioned in the subcutaneous fat layer, not deeper (in thin individuals, the needle should be inserted at a shallower angle, not perpendicularly);
• To administer the insulin, push the syringe plunger fully to deliver the dose over at least 5 seconds;
• Hold an alcohol-soaked cotton swab close to the needle and withdraw the needle from the skin. Apply the alcohol-soaked swab to the injection site for several seconds. Do not rub the skin at the injection site!
• To avoid tissue damage, it is recommended to rotate the injection site with each injection. The next injection site should be at least 1–2 cm away from the previous one.

Mixing Gensulin R solution with suspensions Gensulin N and Gensulin M30

The decision to mix Gensulin R with the above-mentioned suspensions may be made only by a physician.

Use of Gensulin R in cartridges for insulin pens

Gensulin R cartridges can be used with reusable insulin pens of the "pen" type. When filling the insulin pen, attaching the needle, and administering the injection, strictly follow the manufacturer's instructions for the insulin pen. If necessary, insulin can be drawn from the cartridge into a standard insulin syringe and administered as described above (depending on insulin concentration and formulation).

Children

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

Overdose

Insulin overdose causes symptoms of hypoglycemia, including hunger, apathy, dizziness, muscle tremors, disorientation, restlessness, tachycardia, excessive sweating, vomiting, headache, and confusion. In mild hypoglycemia, oral intake of sweet fluids or carbohydrate-rich food is sufficient. Rest is recommended. Patients should always carry sugar cubes, glucose, or candies. Chocolate is not recommended, as the fat content delays glucose absorption.

Severe hypoglycemia may lead to seizures and loss of consciousness, even to fatal outcomes. If the patient is comatose, intravenous glucose must be administered. After insulin overdose, symptoms of hypokalemia (reduced blood potassium concentration) with subsequent myopathy may also occur. In significant hypokalemia, when the patient cannot take food orally, administer 1 mg of glucagon intramuscularly and/or intravenous glucose solution. After regaining consciousness, the patient should consume food. It may also be necessary to continue administering carbohydrates and monitor blood glucose levels, as hypoglycemia may recur after clinical recovery.

Adverse Reactions

In the presence of symptoms of severe hypoglycemia or hyperglycemia with development of ketoacidosis, immediate medical intervention is required. The most commonly observed adverse reactions associated with insulin therapy include hypoglycemia (reduced blood glucose levels) and hyperglycemia (increased blood glucose concentration), as well as local manifestations of allergic reactions.

Hypoglycemia. Signs of moderate hypoglycemia: excessive sweating, dizziness, tremor, hunger sensation, anxiety, tingling in palms, soles, lips, or tongue, difficulty concentrating, drowsiness, sleep disturbances, confusion, mydriasis, blurred vision, speech impairment, 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 are life-threatening conditions. The initial symptoms of acidosis, which develop gradually over several hours or even days, include: drowsiness, facial flushing, thirst, loss of appetite, acetone odor on the breath, increased levels of glucose and ketone bodies in urine, tachypnea, and rapid pulse.

Other adverse effects occurring sporadically during administration of biosynthetic insulins include*: insulin-induced lipodystrophy* (incidence rate from 1/1000 to <1/100) – atrophy or hypertrophy of fatty tissue at the injection site, allergy to insulin, insulin resistance.

Skin and subcutaneous tissue disorders. Frequency unknown: cutaneous amyloidosis; lipodystrophy and cutaneous amyloidosis may occur at the injection site and may delay local absorption of insulin. Regular rotation of injection sites within the same injection area may help reduce or prevent these reactions (see section "Special Instructions").

Local manifestations of allergic reactions – common adverse effect (1/100 to <1/10), including erythema, swelling, or itching at the injection site.

Generalized allergic reactions occur rarely (<1/10,000), but represent potentially dangerous adverse reactions to insulin. These are severe cases involving generalized rash, dyspnea, wheezing, hypotension, increased heart rate, and increased sweating.

Cases of edema have also been reported during insulin therapy, particularly in patients with previously poor metabolic control that improved with insulin treatment. Cases of weight gain have also been reported, as well as injection site reactions (skin discoloration at injection site, bleeding, induration at injection site, swelling at injection site, injection nodules, pain, rash, urticaria, and pustules at injection site), localized pruritus, generalized pruritus, and dizziness.

To avoid tissue damage, it is recommended to rotate injection sites with each injection.

Shelf life.

3 years.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

After opening the individual package, store for up to 28 days at a temperature not exceeding 25 °C. Store protected from light at 2–8 °C. Do not freeze. Keep out of reach of children.

Incompatibilities.

Generally, insulin may be mixed with substances with which its compatibility is known. Medicinal products added to insulin may cause its degradation, for example, preparations containing thiols or sulfites.

Packaging.

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

Prescription category.

Prescription only.

Manufacturer.

BIOTON S.A., Poland (VIOTON S.A., Poland).

Manufacturer's address and location of manufacturing operations.

Legal address: Poland, 02-516, Warsaw, 5 Staroscinska str. (Poland, 02-516, Warsaw, 5 Staroscinska str.).

Manufacturing address: Macierzysz, 12, Poznanska Street, 05-850 Ozarow Mazowiecki, Poland (Macierzysz, 12, Poznanska Street, 05-850 Ozarow Mazowiecki, Poland).