Insuman^® Basal GT (Suspension) Instructions for Use

ATC Code

A10AC01 (Human insulin)

Active Substance

Human insulin isophane rDNA origin

Human insulin isophane rDNA origin (USP United States Pharmacopeia)

Clinical-Pharmacological Group

Intermediate-acting human insulin

Pharmacotherapeutic Group

Intermediate-acting insulin

Pharmacological Action

Hypoglycemic drug, intermediate-acting insulin. Insuman^® Basal GT contains insulin identical in structure to human insulin, obtained by genetic engineering using E.coli K12 135 pINT90d.

Insulin lowers blood glucose concentration, promotes anabolic effects and reduces catabolic effects. It increases glucose transport into cells and glycogen synthesis in muscles and liver, improves pyruvate utilization, inhibits glycogenolysis and gluconeogenesis. Insulin increases lipogenesis in the liver and adipose tissue and suppresses lipolysis. It promotes the entry of amino acids into cells and protein synthesis, increases potassium entry into cells.

Insuman^® Basal GT is a long-acting insulin with a gradual onset of action. After subcutaneous administration, the hypoglycemic effect occurs within 1 hour, reaches a maximum after 3-4 hours, and lasts for 11-20 hours.

Pharmacokinetics

In healthy patients, the plasma half-life (T_1/2) of insulin is approximately 4-6 minutes. In renal failure, the T_1/2 is prolonged.

It should be noted that the pharmacokinetics of insulin do not reflect its metabolic action.

Indications

• Diabetes mellitus requiring insulin therapy.

ICD codes

Dosage Regimen

Suspension

The target blood glucose concentration, the insulin preparations to be used, and the insulin dosing regimen (doses and timing of administration) should be determined and adjusted individually to match the patient’s diet, level of physical activity, and lifestyle.

There are no precisely regulated rules for insulin dosing. However, the average daily insulin dose is 0.5-1 IU/kg of body weight/day, with intermediate-acting human insulin accounting for 40-60% of the required daily insulin dose.

The patient should be given the necessary instructions on the frequency of blood glucose concentration measurement, as well as appropriate recommendations in case of any changes in diet or insulin therapy regimen.

Transition from another type of insulin to Insuman^® Basal GT

When transferring patients from one type of insulin to another, adjustment of the insulin dosing regimen may be required: for example, when switching from insulin of animal origin to human insulin, when switching from one human insulin preparation to another, or when switching from a regimen of soluble human insulin to a regimen including longer-acting insulin.

After switching from insulin of animal origin to human insulin, a reduction in the insulin dose may be required, especially in patients who were previously maintained on fairly low blood glucose concentrations; in patients prone to developing hypoglycemia; in patients who previously required high doses of insulin due to the presence of antibodies to insulin.

The need for dose adjustment (reduction) may arise immediately after switching to the new type of insulin or may develop gradually over several weeks.

When switching from one type of insulin to another and then in the first weeks, careful monitoring of blood glucose concentration is recommended. Patients who required high doses of insulin due to the presence of antibodies are recommended to switch to another type of insulin under medical supervision in a hospital.

Additional dose adjustment

Improvement in metabolic control can lead to increased insulin sensitivity, which may reduce the body’s need for insulin.

A dose change may also be required when the patient’s body weight changes, lifestyle changes (including diet, level of physical activity, etc.), or other circumstances that may increase the predisposition to hypo- or hyperglycemia.

In elderly patients, the need for insulin may decrease. Therefore, initiation of treatment, dose increase, and selection of the maintenance dose in elderly patients with diabetes mellitus should be carried out with caution to avoid hypoglycemic reactions.

In patients with hepatic or renal insufficiency, the need for insulin may decrease.

Administration of Insuman^® Basal GT

Insuman^® Basal GT is usually administered deep subcutaneously 45-60 minutes before a meal. The injection site within one administration area should be changed each time. Changing the insulin administration area (for example, from the abdominal area to the thigh area) should only be done after consultation with a doctor, because insulin absorption and, accordingly, the blood glucose-lowering effect may vary depending on the administration area (for example, the abdominal area or the thigh area).

Insuman^® Basal GT should not be used in various types of insulin pumps (including implanted ones).

Intravenous administration of the drug is absolutely excluded!

Do not mix Insuman^® Basal GT with insulins of different concentrations, with insulins of animal origin, insulin analogs, or other medicines.

Insuman^® Basal GT can be mixed with all human insulin preparations from Sanofi-Aventis group. Insuman^® Basal GT must not be mixed with insulin specifically intended for use in insulin pumps.

It must be remembered that the insulin concentration is 100 IU/ml (for 5 ml vials or 3 ml cartridges), so only plastic syringes designed for this insulin concentration should be used in the case of vials, or OptiPen Pro1 or ClickSTAR pen injectors in the case of cartridges. The plastic syringe must not contain any other drug or its residues.

Rules for using Insuman^® Basal GT in vials

Before the first withdrawal of insulin from the vial, the plastic cap must be removed (the presence of the cap is evidence of an unopened vial). Immediately before withdrawal, the suspension should be mixed well by holding the vial at an acute angle between the palms and gently rotating it (foam should not form). After mixing, the suspension should have a uniform consistency and a milky-white color. The suspension should not be used if it has any other appearance, i.e., if the suspension remains clear, or if flakes or lumps have formed in the liquid itself, at the bottom, or on the walls of the vial. In such cases, another vial that meets the above conditions should be used, and the doctor should be informed.

Before withdrawing insulin from the vial into the syringe, draw a volume of air equal to the prescribed insulin dose and inject it into the vial (not into the liquid). Then the vial together with the syringe must be turned upside down with the syringe downwards and the required amount of insulin must be drawn up. Before injection, air bubbles must be removed from the syringe. At the injection site, a skin fold must be gathered, the needle inserted under the skin, and the insulin injected slowly. After the injection, the needle should be slowly removed and a cotton swab pressed against the injection site for a few seconds. The date of the first withdrawal of insulin from the vial should be written on the vial label.

After opening, vials should be stored at a temperature not exceeding 25°C (77°F) for 4 weeks in a place protected from light and heat.

Rules for using Insuman^® Basal GT in cartridges

Before installing the cartridge (100 IU/ml) into the OptiPen Pro1 and ClickSTAR pen injectors, it should be kept for 1-2 hours at room temperature (injections of cooled insulin are more painful). After this, by gently turning the cartridge (up to 10 times), a homogeneous suspension must be achieved. Each cartridge additionally has three metal balls for faster mixing of its contents. After installing the cartridge into the pen injector, before each insulin injection, the pen injector should be turned over several times to obtain a homogeneous suspension. After mixing, the suspension should have a uniform consistency and a milky-white color. The suspension should not be used if it has any other appearance, i.e., if it remains clear, or if flakes or lumps have formed in the liquid itself, at the bottom, or on the walls of the cartridge. In such cases, another cartridge that meets the above conditions should be used, and the doctor should be informed. Any air bubbles must be removed from the cartridge before injection.

The cartridge is not designed for mixing Insuman^® Basal GT with other insulins. Empty cartridges must not be refilled. If the pen injector breaks, the required dose can be administered from the cartridge using a regular syringe. It must be remembered that the insulin concentration in the cartridge is 100 IU/ml, so only plastic syringes designed for this insulin concentration should be used. The syringe must not contain any other drug or its residues.

After installation, the cartridge should be used within 4 weeks. It is recommended to store cartridges at a temperature not exceeding +25°C (77°F) in a place protected from light and heat. During use, the pen injector should not be stored in the refrigerator (as injections of cooled insulin are more painful). After installing a new cartridge, the correct operation of the pen injector should be checked before injecting the first dose.

Rules for use and handling of the pre-filled SoloStar^® pen

Before first use, the pen must be kept at room temperature for 1-2 hours. Before use, the cartridge inside the pen should be inspected after thorough mixing of the suspension in it by rotating the pen around its axis, holding it at an acute angle between the palms. The pen should only be used if, after mixing, the suspension has a uniform consistency and a milky-white color. The pen should not be used if the suspension in it after mixing has any other appearance, i.e., if it remains clear, or if flakes or lumps have formed in the liquid itself, at the bottom, or on the walls of the cartridge. In such cases, another pen should be used, and the doctor should be informed.

Empty SoloStar^® pens must not be reused; they must be destroyed.

To prevent infection, the pre-filled pen must be used by only one patient; it must not be passed on to another person.

Before using the pen, carefully read the usage information.

Information on the use of the SoloStar^® pen

Before each use, carefully attach a new needle to the pen and perform a safety test.

Only needles that are compatible with SoloStar^® should be used.

Special precautions must be taken to avoid accidents related to needle use and the possibility of infection transmission.

Do not use the SoloStar^® pen if it is damaged or if you are not sure that it will work properly.

Always have a spare SoloStar^® pen available in case of loss or damage of the main SoloStar^® pen.

Pen storage

If the SoloStar^® pen is stored in the refrigerator, it must be taken out 1-2 hours before the intended injection so that the suspension reaches room temperature. Injection of cooled insulin is more painful. Used SoloStar^® pens should be destroyed.

Operation

The SoloStar^® pen must be protected from dust and dirt. The outside of the SoloStar^® pen can be cleaned by wiping it with a damp cloth. Do not immerse, rinse, or lubricate the SoloStar^® pen, as this may damage it.

The SoloStar^® pen accurately doses insulin and is safe to operate.

The pen requires careful handling. Situations where the SoloStar^® pen could be damaged should be avoided. If damage to the SoloStar^® pen is suspected, a new pen must be used.

1. Insulin check

Check the label on the SoloStar^® pen to ensure that it contains the appropriate insulin. For Insuman^® Basal GT, the SoloStar^® pen is white with a green injection button. After removing the pen cap, check the appearance of the insulin contained in it: the suspension after mixing should have a uniform consistency and a milky-white color.

2. Attaching the needle

Only needles that are compatible with the SoloStar^® pen should be used. A new sterile needle should be used for each subsequent injection. After removing the cap, the needle should be carefully screwed onto the pen.

3. Performing the safety test

Before each injection, a safety test must be performed to ensure that the pen and needle are working properly and that air bubbles are removed.

Set a dose equal to 2 units. The outer and inner caps must be removed.

Holding the pen with the needle upwards, gently tap the insulin cartridge with a finger so that all air bubbles move towards the needle.

Fully press the injection button.

If insulin appears at the needle tip, this means that the pen and needle are working correctly.

If insulin does not appear at the needle tip, then step 3 should be repeated until insulin appears at the needle tip.

4. Dose selection

The dose can be set in increments of 1 unit from the minimum dose (1 unit) to the maximum dose (80 units). If a dose exceeding 80 units needs to be administered, 2 or more injections should be given.

The dose window should show “0” after completing the safety test. After this, the required dose can be set.

5. Dose administration

The patient should be informed about the injection technique.

The needle must be inserted under the skin. The injection button should be pressed fully. The button should be held in this position for 10 seconds before removing the needle. This ensures that the selected dose of insulin is fully administered.

6. Removing and destroying the needle

In all cases, the needle should be removed and discarded after each injection. This prevents contamination and/or infection, air entering the insulin container, and insulin leakage.

Special precautions (e.g., one-handed capping technique) should be observed when removing and destroying the needle to reduce the risk of accidents related to needle use and to prevent infection.

After removing the needle, the SoloStar^® pen should be closed with the cap.

Adverse Reactions

Hypoglycemia

Hypoglycemia, the most frequent side effect of insulin therapy, can develop if the dose of insulin administered exceeds the need for it. Severe repeated episodes of hypoglycemia can lead to the development of neurological symptoms, including coma, convulsions. Prolonged or severe episodes of hypoglycemia can be life-threatening for patients.

In many patients, symptoms and manifestations of neuroglycopenia may be preceded by symptoms of reflex (in response to developing hypoglycemia) activation of the sympathetic nervous system. Usually, with a more pronounced or faster decrease in blood glucose concentration, the phenomenon of reflex activation of the sympathetic nervous system and its symptoms are more pronounced.

With a sharp decrease in blood glucose concentration, hypokalemia (complications from the cardiovascular system) or the development of cerebral edema may occur.

The following are adverse events observed in clinical studies, classified by system-organ classes and in order of decreasing frequency: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from the available data).

Allergic reactions uncommon – anaphylactic shock; frequency not known – generalized skin reactions, angioedema, bronchospasm, formation of antibodies to insulin (in rare cases, the presence of insulin antibodies may require a change in the insulin dose to correct the tendency to hyper- or hypoglycemia). Immediate-type allergic reactions to insulin or to the excipients of the drug can be life-threatening and require immediate appropriate emergency measures.

Cardiovascular system frequency not known – decreased blood pressure.

Metabolism and nutrition common – edema; frequency not known – sodium retention. Such effects are possible when improving previously insufficient metabolic control through the use of more intensive insulin therapy.

Visual organ frequency not known – transient visual disturbances (due to temporary changes in the turgor of the eye lenses and their refractive index), temporary worsening of diabetic retinopathy (due to more intensive insulin therapy with a sharp improvement in glycemic control), transient amaurosis (in patients with proliferative retinopathy, especially if they are not receiving treatment with photocoagulation (laser therapy)).

Skin and subcutaneous tissues frequency not known – development of lipodystrophy at injection sites and slowing of local insulin absorption. Constant rotation of injection sites within the recommended administration area may help reduce or stop these reactions.

General disorders and administration site conditions frequency not known – redness, pain, itching, hives, swelling, or inflammatory reaction at the injection site. The most pronounced reactions to insulin at the injection site usually disappear within a few days or a few weeks.

Contraindications

• hypoglycemia;
• hypersensitivity to insulin or to any of the auxiliary components of the drug, except in cases where insulin therapy is vital.

With caution, the drug should be prescribed in renal insufficiency (a decrease in insulin requirement may occur due to reduced insulin metabolism); in elderly patients (gradual decline in renal function may lead to a progressively increasing reduction in insulin requirement); in patients with hepatic insufficiency (insulin requirement may decrease due to reduced gluconeogenesis capacity and decreased insulin metabolism); in patients with severe stenosis of coronary and cerebral arteries (in such patients, hypoglycemic episodes may have particular clinical significance, as there is an increased risk of cardiac or cerebral complications of hypoglycemia); in patients with proliferative retinopathy, especially those not treated with photocoagulation (laser therapy), as they are at risk of transient amaurosis – complete blindness during hypoglycemia; in patients with intercurrent diseases (as insulin requirement increases).

Use in Pregnancy and Lactation

Treatment with Insuman^® Basal GT should be continued if pregnancy occurs. Insulin does not cross the placental barrier.

Effective maintenance of metabolic control throughout pregnancy is mandatory for women who had diabetes before pregnancy, or for women who developed gestational diabetes.

Insulin requirement may decrease in the first trimester of pregnancy and usually increases in the second and third trimesters of pregnancy. Immediately after delivery, insulin requirement decreases rapidly (increased risk of hypoglycemia). During pregnancy and especially after delivery, careful monitoring of blood glucose concentration is mandatory.

If pregnancy occurs or is planned, the doctor must be informed.

During breastfeeding, there are no restrictions on insulin therapy; however, adjustment of insulin dose and diet may be required.

Use in Hepatic Impairment

In patients with hepatic insufficiency, the insulin requirement may decrease.

Use in Renal Impairment

In patients with renal insufficiency, the insulin requirement may decrease.

Geriatric Use

In elderly patients, the insulin requirement may decrease. Therefore, initiation of treatment, dose increase, and selection of the maintenance dose in elderly patients with diabetes mellitus should be carried out with caution to avoid hypoglycemic reactions.

Special Precautions

In case of insufficient glycemic control or a tendency to hyper- or hypoglycemic episodes, before deciding to adjust the insulin dose, it is imperative to check compliance with the prescribed insulin administration regimen, ensure that insulin is injected into the recommended area, check the correctness of the injection technique and other factors that may affect the effect of insulin.

Since the simultaneous use of a number of drugs can weaken or enhance the hypoglycemic effect of Insuman^® Basal GT, other drugs should not be used without special permission from a doctor during its use.

Hypoglycemia

Hypoglycemia occurs if the insulin dose exceeds the requirement for it.

The risk of developing hypoglycemia is high at the beginning of insulin treatment, when switching to another insulin preparation, in patients with a low maintenance blood glucose concentration.

As with the use of other insulins, special caution and intensive blood glucose concentration monitoring should be exercised in patients for whom hypoglycemic episodes may have particular clinical significance, such as patients with severe stenosis of coronary or cerebral arteries (risk of cardiac or cerebral complications of hypoglycemia), as well as in patients with proliferative retinopathy, especially if they have not undergone photocoagulation (laser therapy), as they are at risk of transient amaurosis (complete blindness) during the development of hypoglycemia.

There are certain clinical symptoms and signs that may indicate to the patient or others the developing hypoglycemia. These include: increased sweating, moist skin, tachycardia, cardiac arrhythmias, increased blood pressure, chest pain, tremor, anxiety, feeling of hunger, drowsiness, sleep disturbances, feeling of fear, depression, irritability, unusual behavior, feeling of restlessness, paresthesia in and around the mouth, pale skin, headache, coordination disorders, as well as transient neurological disorders (speech and vision disorders, paralytic symptoms) and unusual sensations. With a progressive decrease in glucose concentration, the patient may lose self-control and even consciousness. In such cases, cold and moist skin may be observed, and convulsions may appear.

Every diabetic patient receiving insulin should learn to recognize unusual symptoms that are signs of developing hypoglycemia. Patients who regularly monitor blood glucose concentration are less at risk of developing hypoglycemia. The patient can correct a noticed decrease in blood glucose concentration by taking sugar or food high in carbohydrates. For this purpose, the patient should always carry 20 g of glucose. In more severe conditions of hypoglycemia, a subcutaneous injection of glucagon is indicated, which can be administered by a doctor or paramedical personnel. After sufficient improvement, the patient should eat. If hypoglycemia cannot be eliminated immediately, a doctor should be urgently called. It is necessary to immediately inform the doctor about the development of hypoglycemia so that he can decide on the need to adjust the insulin dose.

Non-compliance with the diet, missed insulin injections, increased insulin requirement as a result of infectious or other diseases, decreased physical activity can lead to an increase in blood glucose concentration (hyperglycemia), possibly with an increase in the concentration of ketone bodies in the blood (ketoacidosis). Ketoacidosis can develop within hours or days. At the first symptoms of metabolic acidosis (thirst, frequent urination, loss of appetite, fatigue, dry skin, deep and rapid breathing, high concentrations of acetone and glucose in the urine), urgent medical intervention is necessary.

When changing doctors (for example, when hospitalized due to an accident, illness during vacation), the patient must report that he has diabetes.

Patients should be warned about conditions when the symptoms warning of developing hypoglycemia may change, be less pronounced, or be completely absent, for example

• With significant improvement in glycemic control;
• With gradual development of hypoglycemia;
• In elderly patients;
• In patients with autonomic neuropathy;
• In patients with a long history of diabetes;
• In patients simultaneously receiving treatment with certain medications.

Such situations can lead to the development of severe hypoglycemia (possibly with loss of consciousness) before the patient realizes that he is developing hypoglycemia.

If normal or reduced values of glycated hemoglobin are detected, the possibility of recurring, unrecognized (especially nocturnal) episodes of hypoglycemia should be considered.

To reduce the risk of hypoglycemia, the patient is required to strictly follow the prescribed dosage regimen and diet, correctly administer insulin injections, and be warned about the symptoms of developing hypoglycemia.

Factors that increase the predisposition to the development of hypoglycemia require careful monitoring and may require dose adjustment. These factors include

• Change of insulin injection site;
• Increased sensitivity to insulin (e.g., elimination of stress factors);
• Unusual (increased or prolonged) physical activity;
• Intercurrent pathology (vomiting, diarrhea);
• Insufficient food intake;
• Skipping a meal;
• Alcohol consumption;
• Some uncompensated endocrine diseases (such as hypothyroidism and anterior pituitary insufficiency or adrenal cortex insufficiency);
• Simultaneous use of certain medications.

Intercurrent Diseases

In intercurrent diseases, intensive metabolic control is required. In many cases, a urine test for the presence of ketone bodies is indicated; dose adjustment of insulin is often necessary. The insulin requirement often increases. Patients with type 1 diabetes should continue to regularly consume at least a small amount of carbohydrates, even if they can only take a small amount of food or if they have vomiting. Patients should not completely stop insulin administration.

Cross-Immunological Reactions

A fairly large number of patients with hypersensitivity to insulin of animal origin have difficulty switching to human insulin due to a cross-immunological reaction to human insulin and insulin of animal origin. In case of increased patient sensitivity to insulin of animal origin, as well as to m-cresol, the tolerability of Insuman^® Basal GT should be assessed in a clinic using intradermal tests. If an intradermal test reveals hypersensitivity to human insulin (immediate reaction, Arthus type), then further treatment should be carried out under medical supervision.

Effect on Ability to Drive and Operate Machinery

The patient’s ability to concentrate and the speed of psychomotor reactions may be impaired as a result of hypoglycemia or hyperglycemia, as well as due to visual disturbances. This may pose a certain risk in situations where these abilities are important (driving vehicles or operating machinery).

Patients should exercise caution and avoid hypoglycemia while driving a car. This is especially important in patients who have reduced or absent awareness of symptoms indicating the development of hypoglycemia, or who have frequent episodes of hypoglycemia. In such patients, the possibility of driving vehicles or operating machinery should be decided individually.

Overdose

Symptoms insulin overdose, for example, administration of an excessive amount of insulin relative to food intake or energy expenditure, can lead to severe and sometimes prolonged and life-threatening hypoglycemia.

Treatment mild episodes of hypoglycemia (patient is conscious) can be stopped by oral carbohydrate intake. Adjustment of insulin dose, meal regimen, and physical activity may be required. More severe episodes of hypoglycemia with coma, convulsions, or neurological disorders can be stopped by intramuscular or subcutaneous administration of glucagon or intravenous administration of a concentrated dextrose solution. In children, the amount of dextrose administered is set proportionally to the child’s body weight. After increasing the blood glucose concentration, maintenance carbohydrate intake and observation may be required, because after apparent clinical relief of hypoglycemia symptoms, its recurrence is possible. In cases of severe or prolonged hypoglycemia, following an injection of glucagon or administration of dextrose, infusion of a less concentrated dextrose solution is recommended to prevent recurrence of hypoglycemia. In young children, blood glucose concentration must be carefully monitored due to the possible development of severe hyperglycemia.

Under certain conditions, hospitalization of the patient in the intensive care unit is recommended for more careful monitoring of their condition and control of the therapy.

Drug Interactions

Concomitant use with oral hypoglycemic drugs, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, amphetamine, anabolic steroids and androgens, cibenzoline, cyclophosphamide, fenfluramine, guanethidine, ifosfamide, phenoxybenzamine, phentolamine, somatostatin and its analogs, sulfonamides, tetracyclines, tritoqualine or trophosphamide may enhance the hypoglycemic effect of insulin and increase the predisposition to the development of hypoglycemia.

Concomitant use with corticotropin, glucocorticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens and progestogens (e.g., contained in combined oral contraceptives), phenothiazine derivatives, somatotropin, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), thyroid hormones, barbiturates, nicotinic acid, phenolphthalein, phenytoin derivatives, doxazosin may weaken the hypoglycemic effect of insulin.

Beta-blockers, clonidine, lithium salts may either potentiate or weaken the hypoglycemic effect of insulin.

Ethanol may either potentiate or weaken the hypoglycemic effect of insulin. Consumption of ethanol can cause hypoglycemia or reduce already low blood glucose levels to dangerous levels. Tolerance to ethanol in patients receiving insulin is reduced. The doctor should determine the permissible amounts of ethanol consumed.

When used concomitantly with pentamidine, hypoglycemia may develop, which sometimes may turn into hyperglycemia.

When used concomitantly with sympatholytic agents, such as beta-blockers, clonidine, guanethidine and reserpine, a weakening or complete absence of symptoms of reflex (in response to hypoglycemia) activation of the sympathetic nervous system is possible.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature from 2°C (35.6°F) to 8°C (46.4°F). Do not freeze!

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.