Humodar® b100p

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

Composition:

Active substance: recombinant human insulin (100% crystalline protamine insulin);

1 ml of injectable suspension contains 100 IU of recombinant human insulin (100% crystalline protamine insulin);

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

Pharmaceutical form. Injectable suspension.

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. Insulins and analogues of intermediate duration of action.

ATC code A10A C01.

Pharmacological properties.

Pharmacodynamics.

The insulin preparation is identical in structure to human insulin. It ensures reduction of blood glucose levels and enhances tissue glucose uptake. The active ingredient is isophane protamine insulin.

Pharmacokinetics.

HUMODAR® B 100R is characterized by a slow onset and intermediate duration of action. The effect of the preparation begins 1 hour after administration, maximum effect is reached within 4–6 hours, and the duration of action lasts 12–20 hours. The aforementioned duration of action is approximate and depends on the dose of HUMODAR® B 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® B 100R and to any of its excipients, except in cases where desensitization therapy is applied. Intravenous administration is contraindicated.

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of any other medicinal products may enhance or reduce insulin's effect on blood glucose levels. Therefore, combined use of medicinal products with insulin should only be undertaken with prior approval from a physician.

Insulin requirements may increase when using drugs with hyperglycemic activity, such as oral contraceptives, corticosteroids, thyroid hormones and growth hormone, danazol, sympathomimetics (e.g., ritodrine, salbutamol, terbutaline), and diuretics (saluretics). Reduced insulin effect may occur when co-administered with chlorprothixene, diazoxide, heparin, isoniazid, lithium carbonate, nicotinic acid, phenothiazine derivatives, phenytoin, and tricyclic antidepressants.

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

Somatostatin analogs (octreotide, lanreotide), clonidine, reserpine, or salicylates may either enhance or reduce insulin requirements.

Special precautions for use

Any change in the type or brand of insulin must be carried out 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 with animal-sourced insulin. Adjustment of dosage may be necessary from the first dose or during the first few weeks or months of treatment.

In some patients who developed 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 experienced during treatment with animal insulin. Patients who achieve significantly improved blood glucose control (e.g., due to intensified insulin therapy) may subsequently experience fewer or no 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 are changes in the level of physical activity or usual dietary patterns.

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 such reactions. It has been reported that switching injection sites to unaffected skin areas may lead to hypoglycemia. Monitoring of blood glucose levels is recommended after changing injection sites, and dose adjustment of antidiabetic agents may be considered.

Concomitant use with pioglitazone

Cases of heart failure have been reported with 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 with pioglitazone. When using this combination, patients should be monitored for signs and symptoms of heart failure, weight gain, and edema.

Pioglitazone treatment should be discontinued if cardiac symptoms worsen.

Avoid direct contact between the cartridge/vial and the freezer compartment or cooling elements.

A used insulin cartridge or vial 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) of sodium per dose, i.e., essentially sodium-free.

Use during pregnancy or breastfeeding

Insulin does not cross the placental barrier, so there are no restrictions on the treatment of diabetes 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 are planning pregnancy.

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

Immediately after delivery, insulin requirements drop sharply, 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 influence the speed of reaction 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 precautionary measures necessary to avoid hypoglycemia while driving. This is particularly important for patients who have reduced or absent awareness of hypoglycemic warning symptoms or who frequently experience episodes of hypoglycemia. In such circumstances, the appropriateness of driving should be evaluated.

Method of Administration and Dosage

The dosage, administration schedule, and number of injections are determined by a physician based on individual patient needs and specific circumstances. HUMODAR® B 100R is administered by subcutaneous injection, but may also be given by intramuscular injection, although this route is not recommended. HUMODAR® B 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 frequently than once per month, in order to reduce the risk of developing lipodystrophy and cutaneous amyloidosis (see sections "Special Warnings and Precautions" and "Side Effects"). When administering HUMODAR® B 100R, care must be taken to avoid injecting the needle into a blood vessel. After injection, the injection site must not be massaged. Patients should be thoroughly instructed in proper injection techniques. HUMODAR® B 100R may be used in combination with the medicinal product HUMODAR® R 100R. Insulin requirements may change significantly in cases of renal or hepatic insufficiency.

Cartridges. Before use, the cartridge should be gently rolled between the palms 10 times and then inverted 10 times through 180° 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 with insulin pens. When inserting the cartridge into the pen device, follow the manufacturer's instructions. If air bubbles are present, hold the pen with the needle pointing upward and gently tap the side of the cartridge to bring 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 is expelled and a drop of medication 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 each injection, the skin at the injection site should be thoroughly cleaned. The needle should be inserted to the appropriate depth into the subcutaneous tissue, ensuring that it does not enter a blood vessel. The injection site must not be massaged. Immediately after injection, remove the needle from the pen device. This helps maintain sterility and prevents insulin leakage. 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 medication 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 indicating that the vial has not been previously used. Immediately before use, the HUMODAR® B 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. Draw into the syringe an amount of air corresponding to the intended dose 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, form a skin fold, and insert the needle subcutaneously. Then slowly inject the insulin. After injection, carefully withdraw the needle from the skin, apply a cotton swab to the injection site, and hold it in place for several seconds.

Do not use a cartridge or vial if, after mixing, a uniform white suspension is not formed. Do not use a cartridge or vial if, after mixing, white flakes are floating in the suspension or if a white deposit resembling frozen material is visible on the bottom or walls of the cartridge or vial. The cartridge is not designed for refilling or for mixing its contents with other drugs or insulins. Switching from other insulin products should only be done under medical supervision. Patients must strictly adhere to their 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 products, missed meals, vomiting, diarrhea, physical exertion, illnesses that reduce insulin requirements (such as kidney or liver disease, adrenal, pituitary, or thyroid gland hypofunction), changing the injection site (e.g., abdomen, forearm, thigh), or drug interactions that lead to a sharp decrease in blood glucose levels.

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

Mild hypoglycemia can usually be corrected 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, a physician must be contacted immediately. This is particularly dangerous for patients with cerebrovascular disorders or those with significant coronary heart disease in addition to diabetes. Moderate to severe hypoglycemia may be treated by intramuscular or subcutaneous administration of glucagon, followed by oral carbohydrate intake once the patient's condition stabilizes. If there is no response to glucagon, intravenous glucose solution must be administered. 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 he or she regains consciousness.

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

Adverse Reactions.

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 some 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 established, as it results from the combined influence of insulin dose and other factors.

Very rarely, during the first weeks of insulin therapy, leg edema (so-called insulin edema) may occur, associated with fluid retention in the body, which resolves spontaneously.

Immune system disorders.

Local allergic reactions are common (frequency from 1/100 to < 1/10), including injection site reactions: skin redness, swelling, and itching. These usually resolve within a few days to several weeks. Sometimes this condition may not be related to insulin itself, but rather to other factors, such as presence of irritating substances in skin-cleansing agents or inadequate 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, rapid pulse, increased sweating, anaphylactic shock, and angioneurotic edema. Severe cases of generalized allergy are life-threatening. In some exceptional cases of severe allergy to HUMODAR® B 100P, immediate appropriate measures should be taken. Insulin replacement or desensitizing therapy may be required. Insulin resistance.

Skin and subcutaneous tissue disorders.

Cutaneous amyloidosis (frequency unknown) may occur at the injection site and may delay local insulin absorption. Regular rotation of injection sites within the same injection area may help reduce or prevent these reactions (see section "Special Instructions"). At the injection site, atrophy or hypertrophy of fatty tissue (lipodystrophy) may occur. Lipodystrophy at the injection site is uncommon (frequency from 1/1,000 to < 1/100). Transient edema. Continuous rotation of injection sites can help reduce or completely avoid these phenomena during further treatment. Cases of edema development during insulin therapy have been reported, particularly when previous poor metabolic control is improved by intensive insulin therapy.

Neurological disorders.

Reversible peripheral neuropathy.

Shelf life.

3 years.

Storage conditions.

Keep out of reach of children.

Store at 2 °C to 8 °C. Do not freeze.

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

Incompatibility.

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

Packaging.

Suspension for injection, 100 IU/mL, 3 mL in cartridges No. 3, No. 5, or 5 mL in vials No. 1, No. 5, 10 mL in vials No. 1.

Prescription status.

Prescription only.

Manufacturer.

JSC "Insulin Production Enterprise "INDAR".

Manufacturer's address and location of business activity.

5 Zroshuvalna Street, Kyiv, 02099, Ukraine.