Humodar® k25 100r

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HUMODAR® C25 100R (HUMODAR C25 100R)

Composition:

Active substance: recombinant human insulin (25% soluble insulin, 75% crystalline protamine insulin);

1 ml of injection suspension contains 100 IU of recombinant human insulin (25% soluble insulin, 75% crystalline protamine insulin);

Excipients: protamine sulfate, m-cresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium chloride, sodium hydroxide, hydrochloric acid concentrated, water for injections.

Pharmaceutical form. Suspension for injection.

Main physicochemical properties: white or almost white suspension, which upon standing forms a white or almost white sediment and a colorless or almost colorless supernatant liquid; the sediment readily resuspends upon gentle shaking.

Pharmacotherapeutic group.

Antidiabetic agents. Combination of short- and intermediate-acting insulins.

ATC code A10AD01.

Pharmacological properties.

Pharmacodynamics.

The insulin preparation is structurally identical to human insulin. It reduces blood glucose levels and enhances tissue glucose uptake. The active ingredients are – neutral insulin solution and isophane protamine insulin.

Pharmacokinetics.

HUMODAR® K25 100R is characterized by a rapid onset and intermediate duration of action. The effect begins 30–45 minutes after administration, maximum effect is reached within 1–3 hours, and the duration of action lasts 12–16 hours. The aforementioned duration of action is approximate and depends on the dose of HUMODAR® K25 100R and individual patient characteristics.

Clinical characteristics.

Indications.

For the treatment of patients with diabetes mellitus who require insulin to maintain normal blood glucose levels.

Contraindications.

Hypoglycemia, increased sensitivity to the drug HUMODAR® K25 100R or to any of the excipients of the drug, except in cases where desensitization therapy is applied. Intravenous administration is contraindicated.

Interaction with other medicinal products and other forms of interactions.

The concomitant use of any other medicinal products may enhance or weaken the effect of insulin on blood glucose levels. Therefore, the concurrent use of medicinal products with insulin is possible only upon agreement with a physician.

The need for insulin may increase when using medicinal products with hyperglycemic activity, such as oral contraceptives, corticosteroids, thyroid hormones and growth hormone, danazol, sympathomimetics (e.g., ritodrine, salbutamol, terbutaline), and diuretics (saluretics). Weakening of insulin action may occur when co-administered with chlorpromazine, diazoxide, heparin, isoniazid, lithium carbonate, nicotinic acid, phenothiazine derivatives, phenytoin, and tricyclic antidepressants.

The need for insulin may decrease when using medicinal products with hypoglycemic activity, such as oral hypoglycemic agents, salicylates (e.g., acetylsalicylic acid), sulfonamides, certain antidepressants (monoamine oxidase inhibitors), certain angiotensin-converting enzyme inhibitors (captopril, enalapril), angiotensin II receptor blockers, non-selective beta-blockers, or alcohol. Enhanced insulin action may occur when used concomitantly with anabolic steroids, tetracyclines, clofibrate, cyclophosphamide, fenfluramine, or ethanol-containing preparations.

Somatostatin analogs (octreotide, lanreotide), clonidine, reserpine, or salicylates may either enhance or weaken the need for insulin.

Special precautions for use.

Any change in the type or brand of insulin must be made under strict medical supervision.

Changes in concentration, brand (manufacturer), type (rapid-acting, intermediate-acting, long-acting, etc.), species (animal-sourced insulin, human insulin, human insulin analog), and/or method of production (recombinant DNA insulin or animal-sourced insulin) may require a change in dosage.

Dosage when using human insulin may differ from that required when using animal-sourced insulin. Dose adjustments may be necessary from the first dose or over the first few weeks or months.

In some patients who have experienced hypoglycemic reactions after switching from animal-sourced insulin to human insulin, early warning symptoms of hypoglycemia have been reported to be less pronounced or different from those previously observed during treatment with animal insulin. Patients who achieve significantly improved blood glucose levels (e.g., due to intensified insulin therapy) may no longer experience some or any of the early warning symptoms of hypoglycemia, and they should be informed accordingly. Conditions in which early warning symptoms of hypoglycemia may be less specific or less pronounced include long-standing diabetes, diabetic neuropathy, or concomitant use of medications such as beta-adrenergic blockers.

Untreated hypoglycemic or hyperglycemic reactions may lead to loss of consciousness, coma, and may be fatal.

Use of incorrect doses or abrupt discontinuation of treatment, especially in insulin-dependent diabetes, may lead to hyperglycemia and ketoacidosis—conditions that are potentially fatal.

Antibody formation may occur during treatment with human insulin, although to a lesser extent than with purified animal-sourced insulin.

Insulin requirements may change significantly in diseases of the adrenal glands, pituitary gland, or thyroid gland, and in the presence of renal or hepatic insufficiency.

Insulin requirements may also increase during illness or emotional stress.

Dose adjustments may be necessary when there is a change in the level of physical activity or usual dietary pattern.

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. Cases have been reported where changing the injection site to an unaffected area of skin resulted in 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.

Combination therapy with pioglitazone

Cases of heart failure have been reported with the concomitant use of pioglitazone and insulin, particularly in patients with risk factors for heart failure. This information should be taken into account when prescribing the combination of insulin and pioglitazone. When using this combination, patients should be monitored for signs and symptoms of heart failure, weight gain, and edema. Treatment with pioglitazone should be discontinued if cardiac symptoms worsen.

Avoid direct contact of the cartridge or vial with the freezer compartment or ice packs.

The cartridge or vial of insulin in use may be stored at room temperature (not above 30 °C) for up to 4 weeks, provided it is protected from direct heat and light.

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

Use during pregnancy or breastfeeding.

Insulin does not cross the placental barrier; therefore, there are no restrictions on insulin treatment during pregnancy.

Pregnant women with insulin-dependent diabetes or gestational diabetes receiving insulin therapy require careful monitoring throughout pregnancy.

Insulin requirements usually decrease during the first trimester of pregnancy and then increase during the second and third trimesters. Patients with diabetes should inform their physician if they become pregnant or plan to become pregnant.

During pregnancy, patients with diabetes require careful monitoring of blood glucose levels and overall health status.

Insulin requirements decrease sharply immediately after delivery, increasing the risk of hypoglycemia. However, insulin requirements quickly return to pre-delivery levels.

Breastfeeding women with diabetes may require adjustments in insulin dosage and/or dietary regimen.

Ability to affect reaction speed when driving or operating machinery.

The ability of patients using insulin to concentrate and react may be impaired as a result of hypoglycemia. This may constitute a risk factor, including while driving a vehicle or operating machinery.

Patients should be informed about the specific preventive measures necessary to avoid hypoglycemia while driving. This is particularly important for patients with diminished or absent awareness of hypoglycemic warning symptoms or those who frequently experience episodes of hypoglycemia. In such circumstances, the appropriateness of driving should be carefully evaluated.

Method of Administration and Dosage.

The dosage, administration schedule, and number of injections are determined by a physician based on individual patient needs. HUMODAR® K25 100R is administered by subcutaneous injection, but may also be given by intramuscular injection, although this route is not recommended. HUMODAR® K25 100R must not be administered intravenously. Subcutaneous injections should be administered into the shoulder, thigh, buttocks, or abdomen. The injection site should be rotated to avoid repeated injections at the same site more than once per month, in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections "Special Warnings and Precautions" and "Adverse Reactions"). When administering HUMODAR® K25 100R, care must be taken to avoid injecting into a blood vessel. After injection, the injection site must not be massaged. Patients should be thoroughly instructed in the proper technique for performing injections. HUMODAR® K25 100R is a ready-to-use mixture of soluble and isophane insulin, designed to eliminate the need for patients to mix insulin preparations manually. Insulin requirements may change significantly in cases of renal or hepatic insufficiency.

Cartridges. Before use, the cartridge should be rolled 10 times between the palms and inverted 180° ten times to ensure proper mixing of the contents. Before inserting the cartridge into the pen device, the uniformity of the suspension should be checked, and the mixing procedure repeated if necessary, as described above. After mixing, the preparation should appear as a uniform, milky-white suspension.

Before using the pen device, wash hands and disinfect the rubber membrane of the cartridge.

The cartridge is intended for use only in insulin pens. When inserting the cartridge into the pen device, follow the manufacturer's instructions for the pen.

If air bubbles are present in the cartridge, hold the pen device with the needle pointing upward and gently tap the side of the cartridge to bring the bubbles to the surface. While keeping the pen in an upright position, expel 2 units of insulin through the needle. Repeat this procedure until all air bubbles are removed and a drop of the preparation appears at the needle tip. The presence of very small air bubbles is acceptable; however, a large number of bubbles may affect the accuracy of the insulin dose administered.

Before insulin injection, the skin at the injection site should be thoroughly cleaned. The needle should be inserted to the appropriate depth into the subcutaneous tissue, taking care not to enter a vein. The injection site must not be massaged. Immediately after injection, the needle should be removed from the pen device. This ensures sterility and prevents leakage of insulin. The mixing procedure must be repeated before each subsequent injection without removing the cartridge from the pen. Before each injection, ensure that a drop of insulin appears at the needle tip. Do not use the cartridge if the insulin is nearly depleted and the leading edge of the plunger is at or beyond the colored line.

Before each injection, always check the cartridge label to confirm that the insulin name and type correspond to the one prescribed by your physician.

Vials. Before the first withdrawal of insulin from the vial, remove the plastic cap that indicates the vial has not been used. Immediately before use, the HUMODAR® K25 100R suspension must be thoroughly mixed without creating foam by rolling the vial gently between the palms. After mixing, the suspension should become uniform and milky-white in appearance. According to the prescribed dose, draw air into the syringe equal to the dose volume and inject it into the insulin vial (not into the liquid). Invert the insulin vial together with the syringe and withdraw the required amount of insulin suspension. Remove any air bubbles from the syringe. Disinfect the injection site, pinch the skin to form a skin fold, and insert the needle under the skin. Then slowly inject the insulin. After injection, carefully withdraw the needle from the skin, press the injection site with a cotton swab, and hold for several seconds. Do not use the cartridge/vial if a uniform white suspension does not form after mixing. Do not use the cartridge/vial if, after mixing, white clumps are floating in the suspension or if a white deposit resembling frozen mass is visible on the bottom or sides of the cartridge/vial. The cartridge is not designed for refilling or for mixing its contents with other medications or insulins.

Switching from other insulin preparations should only be done under medical supervision. Patients must strictly follow the physician's instructions regarding insulin dosage, diet, and physical activity.

Children.

Dosage, administration schedule, and number of injections for children are determined by a physician based on individual needs in each specific case.

Overdose.

Insulin overdose may result from: absolute insulin overdose, switching insulin preparations, missed meals, vomiting, diarrhea, physical exertion, illnesses that reduce insulin requirements (kidney or liver disease, adrenal insufficiency, hypopituitarism, or hypothyroidism), change in injection site (e.g., abdomen, forearm, thigh), or drug interactions that lead to a rapid decrease in blood glucose levels.

Symptoms of hypoglycemia include lethargy, confusion, tachycardia, headache, sweating, and nausea.

Mild hypoglycemia is usually treatable by oral administration of glucose or sugar-containing products. It is advisable to always carry at least 20 g of glucose (dextrose). If hypoglycemia cannot be promptly corrected, immediate medical assistance must be sought. This is particularly dangerous for patients with cerebrovascular disorders or those with severe coronary heart disease in addition to diabetes. Moderate to severe hypoglycemia may be treated by intramuscular or subcutaneous administration of glucagon, followed by oral intake of carbohydrates once the patient's condition stabilizes. If there is no response to glucagon, intravenous administration of glucose solution is required. In comatose patients, glucagon should be administered intramuscularly or subcutaneously. In the absence of glucagon or if there is no response to glucagon, intravenous glucose solution must be administered. The patient should be fed as soon as consciousness is regained.

Continued carbohydrate intake and medical monitoring may be necessary, as hypoglycemia may recur after apparent clinical improvement.

Side effects.

Disorders of metabolism and nutrition.

Hypoglycemic reaction may occur in case of administration of too high insulin dose, skipping meals, excessive physical exertion, or alcohol consumption. Hypoglycemia is characterized by a decrease in blood glucose level below 50 mg/dL.

Severe hypoglycemia may lead to loss of consciousness and, in individual cases, to fatal outcome. Hypoglycemia is the most common adverse effect of insulin therapy in patients with diabetes mellitus. The exact frequency of hypoglycemic episodes cannot be determined, as it results from the combined influence of insulin dose and other factors.

Very rarely, during the first weeks of insulin therapy, swelling of the legs (so-called insulin edema) related to fluid retention in the body may occur; these usually resolve spontaneously.

Immune system disorders.

Local allergic reactions are common (frequency from 1/100 to < 1/10), including injection site reactions such as skin redness, swelling, and itching. These reactions usually resolve within several days to several weeks. Sometimes this condition may not be related to insulin itself but to other factors, for example, presence of irritant substances in skin cleansing agents or improper injection technique.

Systemic allergic reaction is very rare (< 1/10,000), but potentially serious, representing a generalized allergic reaction to insulin.

It may manifest as generalized skin rash, erosive mucosal lesions, nausea, chills, dyspnea, wheezing, decreased blood pressure, tachycardia, increased sweating, anaphylactic shock, and angioedema. Severe cases of generalized allergy are life-threatening. In rare cases of severe allergy to HUMODAR® K25 100P, appropriate measures must be taken immediately. It may be necessary to switch to another insulin or initiate desensitization therapy. Insulin resistance.

Skin and subcutaneous tissue disorders.

Cutaneous amyloidosis (frequency unknown) may occur at the injection site and delay local insulin absorption. Regular rotation of injection sites within the same injection area may help reduce or prevent these reactions (see section "Special precautions"). Atrophy or hypertrophy of subcutaneous fat tissue (lipodystrophy) may occur at the injection site. Lipodystrophy at the injection site is uncommon (frequency from 1/1000 to < 1/100). Transient edema. Consistently changing the injection site may help reduce or completely avoid these phenomena during further treatment. Cases of edema development have been reported during insulin therapy, particularly when previous poor metabolic control improved with intensive insulin therapy.

Neurological disorders.

Reversible peripheral neuropathy.

Shelf life.

2.5 years.

Storage conditions.

Keep out of reach of children.

Store at a temperature between 2 °C and 8 °C. Do not freeze.

Do not use the medicinal product after the expiry date stated on the packaging.

Incompatibility.

HUMODAR® K25 100P must not be mixed with other medicinal products.

Packaging.

Suspension for injection, 100 IU/mL, 3 mL in cartridges, pack of 3 or 5; or 5 mL in vials, pack of 1 or 5; or 10 mL in vials, pack of 1.

Prescription status.

Prescription only.

Manufacturer.

JSC "Insulin Production Plant "INDAR".

Manufacturer's address and location of business activity.

5 Zroshuvalna Street, Kyiv, 02099, Ukraine.