Insuman^® Rapid GT (Solution) Instructions for Use

ATC Code

A10AB01 (Human insulin)

Active Substance

Insulin soluble [human genetically engineered] (SP State Pharmacopoeia)

Clinical-Pharmacological Group

Short-acting human insulin

Pharmacotherapeutic Group

Short-acting insulin

Pharmacological Action

Hypoglycemic drug, short-acting insulin. Insuman^® Rapid GT contains insulin, identical in structure to human insulin and obtained by genetic engineering using the K12 strain of E. coli.

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

Insuman^® Rapid GT is an insulin with a rapid onset and short duration of action. After subcutaneous administration, the hypoglycemic effect occurs within 30 minutes, reaches a maximum in 1-4 hours, and lasts for 7-9 hours.

Pharmacokinetics

Information on the pharmacokinetics of Insuman^® Rapid GT is not provided.

Indications

• Diabetes mellitus requiring insulin therapy;
• Treatment of diabetic coma and ketoacidosis;
• Achievement of metabolic compensation in patients with diabetes mellitus during surgical interventions (before surgery, during surgery and in the postoperative period).

ICD codes

Dosage Regimen

Solution

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, according to the patient’s diet, level of physical activity and lifestyle.

There are no precisely regulated rules for insulin dosing. However, the average daily dose of insulin is 0.5-1 IU/kg of body weight/day, with long-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 and appropriate recommendations in case of any changes in diet or insulin therapy regimen.

In the treatment of severe hyperglycemia or, in particular, ketoacidosis, insulin administration is part of a comprehensive treatment regimen that includes measures to protect patients from possible serious complications due to a relatively rapid decrease in blood glucose concentration. This treatment regimen requires careful monitoring in the intensive care unit (determination of metabolic status, acid-base balance and electrolyte balance, monitoring of vital signs).

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

When transferring a patient 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 at 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 a 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 after the switch, careful monitoring of blood glucose concentration is recommended. In patients who required high doses of insulin due to the presence of antibodies, it is recommended to switch to another type of insulin under medical supervision in a hospital.

Additional dose adjustment

Improvement in metabolic control may 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, when lifestyle changes (including diet, level of physical activity, etc.), or other circumstances that may contribute to an increased predisposition to hypo- or hyperglycemia.

In elderly patients, the need for insulin may decrease. Initiation of treatment, dose increase and selection of a 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^® Rapid GT

Insuman^® Rapid GT is usually administered deep subcutaneously 15-20 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 abdomen to the thigh) should be done only after consultation with a doctor, because the absorption of insulin and, accordingly, the effect of lowering blood glucose concentration may change depending on the administration area.

Insuman^® Rapid GT can be administered intravenously. Intravenous insulin therapy should be carried out in a hospital setting or in conditions where similar monitoring and treatment conditions can be provided.

Insuman^® Rapid GT should not be used in various types of insulin pumps (including implanted ones) that use silicone tubes.

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

Insuman^® Rapid GT can be mixed with all human insulin preparations of the Sanofi-Aventis group. Insuman^® Rapid GT should not be mixed with insulin specifically intended for use in insulin pumps.

It must be remembered that the concentration of insulin in Insuman^® Rapid GT is 100 IU/ml (for 5 ml vials or 3 ml cartridges), so it is necessary to use only plastic syringes designed for this concentration of insulin in the case of using vials, or OptiPen Pro1 or ClickSTAR pen-injectors in the case of using cartridges. The plastic syringe must not contain any other drug or its residues.

Rules for using Insuman^® Rapid 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). The injection solution must be absolutely clear and colorless, without visible foreign particles.

Before withdrawing insulin from the vial, draw a volume of air into the syringe equal to the prescribed dose of insulin and inject it into the vial (not into the liquid). Then the vial together with the syringe should be turned upside down and the required amount of insulin should be drawn up. Before injection, air bubbles must be removed from the syringe.

At the injection site, it is necessary to take a skin fold, insert the needle under the skin and slowly inject the insulin. After the injection, the needle should be slowly removed and a cotton swab should be pressed to 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^® Rapid GT in cartridges

Before installing the cartridge (100 IU/ml) into the OptiPen Pro1 and ClickSTAR pen-injectors, it should be kept at room temperature for 1-2 hours (injections of cooled insulin are more painful). Any air bubbles must be removed from the cartridge before injection.

The cartridge is not designed for mixing Insuman^® Rapid 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 concentration of insulin in the cartridge is 100 IU/ml, so it is necessary to use only plastic syringes designed for this concentration of insulin. The syringe must not contain any other drug or its residues.

After installing the cartridge, it should be used within 4 weeks. It is recommended to store the pen-injector with the installed cartridge at a temperature not exceeding +25°C (77°F) in a place protected from light and heat, but not in the refrigerator (since 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-injector

Insuman^® Rapid GT, solution for injection in a disposable SoloStar^® pen-injector is intended for subcutaneous administration only.

Before first use, the pen-injector should be kept at room temperature for 1-2 hours. Before use, the cartridge inside the pen-injector should be inspected. It should be used only if the insulin solution is absolutely clear, colorless, and without visible foreign particles.

Empty SoloStar^® pen-injectors must not be reused; they must be destroyed.

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

Before using the pen-injector, carefully read the usage information.

Information on the use of the SoloStar^® pen-injector

Before each use, carefully attach a new needle to the pen-injector 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 the use of the needle and the possibility of infection transmission.

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

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

Storage of the pen-injector

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

Operation

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

The SoloStar^® pen-injector accurately doses insulin and is safe to use.

The pen-injector requires careful handling. Situations in which the SoloStar^® pen-injector may be damaged should be avoided. If damage to the SoloStar^® pen-injector is suspected, a new pen-injector should be used.

1. Insulin check

Check the label on the SoloStar^® pen-injector to ensure that it contains the appropriate insulin. For Insuman^® Rapid GT, the SoloStar^® pen-injector is white with a yellow injection button with a relief ring on it. After removing the cap of the pen-injector, check the appearance of the insulin contained in it: the solution must be absolutely clear, colorless, without visible foreign particles.

2. Attaching the needle

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

3. Performing a safety test

Before each injection, a safety test must be performed to ensure that the pen-injector 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.

With the pen-injector needle up, gently tap the insulin cartridge with your finger so that all air bubbles are directed towards the needle.

Fully press the injection button.

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

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

4. Dose selection

The dose can be set with an accuracy of 1 unit from the minimum dose (1 unit) to the maximum dose (80 units). If it is necessary to administer a dose exceeding 80 units, 2 or more injections should be given.

The dose window should show “0” after the safety test is completed. Then set the required dose.

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 until the needle is removed. This ensures that the selected dose of insulin is administered completely.

6. Needle removal and disposal

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 disposing of the needle to reduce the risk of accidents related to the use of the needle and to prevent infection.

After removing the needle, close the SoloStar^® pen-injector with the cap.

Adverse Reactions

Hypoglycemia

Hypoglycemia, the most common 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 and 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 unknown (cannot be estimated from the available data).

Allergic reactions uncommon – anaphylactic shock; frequency unknown – generalized skin reactions, angioedema, bronchospasm, formation of antibodies to insulin (in rare cases, the presence of antibodies to insulin 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 require immediate appropriate emergency measures.

From the cardiovascular system frequency unknown – decreased blood pressure.

From metabolism and nutrition common – edema; frequency unknown – sodium retention. Such effects are possible when improving previously insufficient metabolic control through the use of more intensive insulin therapy.

From the organ of vision frequency unknown – transient visual disturbances (due to a temporary change 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)).

From the skin and subcutaneous tissues frequency unknown – development of lipodystrophy at the 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 unknown – 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 reactions to insulin or to any of the excipients of the drug.

With caution the drug should be used in renal failure (a decrease in the need for insulin is possible due to a decrease in insulin metabolism), in elderly patients (a gradual decrease in renal function may lead to a constant decrease in the need for insulin), in patients with hepatic failure (the need for insulin may decrease due to a decrease in the ability for gluconeogenesis and a decrease in insulin metabolism), in patients with severe stenosis of the coronary and cerebral arteries (hypoglycemic episodes may be of particular clinical importance, since there is an increased risk of cardiac or cerebral complications of hypoglycemia), in patients with proliferative retinopathy (especially those not receiving photocoagulation (laser therapy), since they have a risk of transient amaurosis – complete blindness during hypoglycemia), in patients with intercurrent diseases (the need for insulin often increases).

Use in Pregnancy and Lactation

Treatment with Insuman^® Rapid 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.

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

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

Use in Hepatic Impairment

The drug should be used with caution in patients with hepatic insufficiency (the insulin requirement may decrease due to reduced gluconeogenesis capacity and decreased insulin metabolism).

Use in Renal Impairment

The drug should be used with caution in renal insufficiency (a decrease in insulin requirement is possible due to reduced insulin metabolism).

Geriatric Use

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

Special Precautions

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

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

Hypoglycemia

Hypoglycemia occurs if the insulin dose exceeds the requirement. The risk of developing hypoglycemia is high at the beginning of insulin treatment, when switching to another insulin preparation, and 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 the 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) if hypoglycemia develops.

There are certain clinical symptoms and signs that may indicate to the patient or others that hypoglycemia is developing. 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 be taught to recognize symptoms that are signs of developing hypoglycemia. Patients who regularly monitor their blood glucose concentration are less at risk of developing hypoglycemia. The patient can self-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 cases 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 a meal. If hypoglycemia cannot be eliminated immediately, a doctor should be urgently called. The doctor must be immediately informed 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, and decreased physical activity can lead to an increase in blood glucose concentration (hyperglycemia), possibly with an increase in the level 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 they have diabetes mellitus.

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 mellitus;
• In patients simultaneously receiving treatment with certain medications.

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

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 dietary regimen, correctly administer insulin injections, and be warned about the symptoms of developing hypoglycemia.

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

• Changing the 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 disorders (such as hypothyroidism and anterior pituitary insufficiency or adrenal cortex insufficiency);
• Concurrent use of certain medications.

Intercurrent Diseases

During 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 are 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. If the patient has increased sensitivity to insulin of animal origin, as well as to m-cresol, the tolerance of Insuman^® Rapid GT should be assessed in a clinic using intradermal tests. If an intradermal test reveals hypersensitivity to human insulin (an immediate Arthus-type reaction), further treatment should be carried out under clinical 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 such abilities are important (driving vehicles or operating machinery). Patients should exercise caution and avoid hypoglycemia while driving a car. This is especially important for patients who have reduced or absent awareness of symptoms indicating developing hypoglycemia, or who have frequent episodes of hypoglycemia. For 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 managed by oral carbohydrate intake. Adjustment of the insulin dose, meal regimen, and physical activity may be required. More severe episodes of hypoglycemia with coma, convulsions, or neurological disorders can be managed by intramuscular or subcutaneous injection 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 the blood glucose concentration increases, maintenance carbohydrate intake and observation may be required, because after the apparent clinical elimination of hypoglycemia symptoms, its recurrence is possible. In cases of severe or prolonged hypoglycemia, following an injection of glucagon or dextrose administration, infusion of a less concentrated dextrose solution is recommended to prevent the 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 developing hypoglycemia.

Concomitant use with corticotropin, glucocorticoids, 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 potentiate or weaken the hypoglycemic effect of insulin. Ethanol consumption can cause hypoglycemia or reduce an already low blood glucose level to a dangerous level. Tolerance to ethanol in patients receiving insulin is reduced. The doctor should determine the permissible amounts of ethanol consumption.

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

When used concomitantly with sympatholytic agents, such as beta-blockers, clonidine, guanethidine, and reserpine, the symptoms of reflex (in response to hypoglycemia) activation of the sympathetic nervous system may be weakened or completely absent.

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, 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.