Novorapid FlexPen solution in syringe pen 100 IU/ml 3 ml No. 5

Pharmacological properties of the drug Novorapid Flexpen

NovoRapid FlexPen is an analogue of short-acting human insulin produced by biotechnology (the amino acid proline at position 28 of the B chain is replaced by aspartic acid). The hypoglycemic effect of insulin aspart is to improve the uptake of glucose into tissues after insulin binds to the receptors of muscle and fat cells, as well as to simultaneously inhibit the release of glucose from the liver. The effect of NovoRapid FlexPen occurs earlier than with the administration of soluble human insulin, and the level of glucose in the blood becomes lower during the first 4 hours after ingestion. When administered subcutaneously, the duration of action of NovoRapid FlexPen is shorter compared to soluble human insulin and occurs 10–20 minutes after administration. The maximum effect develops between 1 and 3 hours after injection. Duration of action: 3–5 hours. Adults. The results of clinical studies in patients with type 1 diabetes mellitus showed that with the administration of the drug NovoRapid FlexPen, the glucose level after meals is lower than with the administration of human insulin. Elderly and senile people. A randomized, double-blind study conducted in 19 patients with type II diabetes aged 65–83 years (mean age 70 years) compared the pharmacodynamics and pharmacokinetics of insulin aspart and soluble human insulin. The relative differences in the values of pharmacodynamics indicators (maximum rate of glucose infusion - GIRmax and AUC rate of its infusion within 120 minutes after administration of insulin preparations - AUC GIR 0-120 min) between insulin aspart and human insulin were the same as in practically healthy individuals and patients diabetes under 65 years of age Children and adolescents. In children treated with NovoRapid FlexPen, the effectiveness of long-term control of blood glucose levels is the same as when treated with soluble human insulin. A clinical study of children aged 2–6 years compared the effectiveness of glycemic control between soluble human insulin administered before meals and insulin aspart administered after meals, and also determined pharmacokinetics and pharmacodynamics in children aged 6–12 years and adolescents 13–17 years old. years. The pharmacodynamic profile of insulin aspart was similar in children and adults. The results of clinical studies in patients with type I diabetes mellitus showed that when using insulin aspart, the risk of developing hypoglycemia at night is lower compared to soluble human insulin; As for the frequency of hypoglycemia during the day, no significant differences were noted. Pregnancy period. A clinical study conducted in 322 pregnant women with type 1 diabetes mellitus compared the safety and effectiveness of insulin aspart and human insulin. 157 people 165 people received insulin aspart. - human insulin. However, no negative effects of insulin aspart on a pregnant woman, fetus or newborn were detected compared to human insulin. In addition, in a study conducted on 27 pregnant women with diabetes, 14 people. 13 people received insulin aspart. - human insulin. The study results showed a similar level of safety for these insulin preparations. When calculating the dose (in moles), insulin aspart is equivalent to soluble human insulin. Pharmacodynamics. Substitution of the amino acid proline in position B-28 of the insulin molecule in NovoRapid FlexPen with aspartic acid leads to a decrease in the formation of hexamers, which is noted when soluble human insulin is administered. Consequently, NovoRapid FlexPen is absorbed more quickly into the bloodstream from subcutaneous fat tissue compared to soluble human insulin. The time to reach the maximum concentration of insulin in the blood is on average half that when injecting soluble human insulin. The maximum concentration of insulin in the blood of patients with type I diabetes mellitus 492±256 pmol/l is achieved 30–40 minutes after subcutaneous administration of NovoRapid FlexPen at the rate of 0.15 U/kg body weight. Insulin levels return to baseline 4–6 hours after administration. The intensity of absorption is slightly lower in patients with type II diabetes mellitus. Therefore, the maximum insulin concentration in such patients is slightly lower - 352±240 pmol/l and is achieved later - on average after 60 minutes (50-90) minutes. When administering the drug NovoRapid FlexPen, the variability in the time to reach maximum concentration in the same patient is significantly less, and the variability in the level of maximum concentration is greater than when administering human soluble insulin. Children and teenagers. The pharmacokinetics and pharmacodynamics of NovoRapid FlexPen were studied in children (2–6 years and 6–12 years) and adolescents (13–17 years) with type I diabetes. Insulin aspart was rapidly absorbed in both age groups, and the time to reach Cmax in the blood was the same as in adults. However, the Cmax level was different in children of different ages, which indicates the importance of individual selection of doses of NovoRapid FlexPen. Elderly and senile people. In patients with type II diabetes aged 65–83 years (average age - 70 years), the relative differences in pharmacokinetic parameters between insulin aspart and human insulin were the same as in practically healthy individuals and diabetic patients under the age of 65 years. In patients in the older age group, the rate of absorption is reduced, as evidenced by a longer time to reach Cmax of insulin - 82 minutes with an interquartile range of 60–120 minutes, while its Cmax values were the same as in patients with type II diabetes under the age of 65 years. and slightly lower than in patients with type I diabetes. Liver dysfunction. In 24 people with varying levels of liver function (from normal to severe liver failure), the pharmacokinetics of insulin aspart was determined after a single dose. In patients with moderate and severe liver dysfunction, the intensity of absorption decreased and was more variable, as evidenced by an increase in the time to reach Cmax to 85 minutes (in individuals with normal liver function this time is 50 minutes). AUC, Cmax and CL/F values in subjects with reduced liver function were the same as in subjects with normal liver function. Renal dysfunction. In 18 individuals with varying levels of renal function (from normal to severe renal failure), the pharmacokinetics of insulin aspart was determined after a single dose. At different levels of creatinine clearance, there were no significant differences in the AUC, Cmax and CL/F values of insulin aspart. Data on patients with moderate to severe renal impairment were limited. Patients with renal failure undergoing hemodialysis were not studied.

INSULIN NOVORAPID FLEXPEN

special instructions

Before traveling for long periods of time due to jet lag, the patient should consult with their physician, as jet lag means that the patient must eat and take insulin at different times.
Hyperglycemia

An insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia and diabetic ketoacidosis. Typically, symptoms of hyperglycemia appear gradually over several hours or days. Symptoms of hyperglycemia include nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, increased urine output, thirst and loss of appetite, as well as the smell of acetone in the exhaled air. Without appropriate treatment, hyperglycemia can lead to death.

Hypoglycemia

Skipping meals, unplanned increased physical activity, or an insulin dose that is too high for the patient's needs can lead to hypoglycemia.

After compensation of carbohydrate metabolism, for example, with intensified insulin therapy, patients may experience changes in their typical symptoms that are precursors of hypoglycemia, of which patients should be informed.

The usual warning symptoms may disappear with prolonged diabetes mellitus.

A consequence of the pharmacodynamic properties of short-acting insulin analogues is that the development of hypoglycemia with their use may begin earlier than with the use of soluble human insulin.

Since NovoRapid® FlexPen® should be used in direct connection with food intake, the high rate of onset of the drug’s effect should be taken into account when treating patients with concomitant diseases or taking medications that slow down the absorption of food. Concomitant diseases, especially infectious ones and those accompanied by fever, usually increase the body's need for insulin. Dose adjustment of the drug may also be required if the patient has concomitant diseases of the kidneys, liver, dysfunction of the adrenal glands, pituitary gland or thyroid gland.

When transferring a patient to other types of insulin, early symptoms that are precursors of hypoglycemia may become less pronounced compared to those when using the previous type of insulin.

Transferring the patient from other insulin preparations

Transferring a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under strict medical supervision. If the concentration, type, manufacturer and type (human insulin, animal insulin, human insulin analogue) of insulin preparations and/or manufacturing method change, it may be necessary to change the dose or increase the frequency of injections compared to previously used insulin preparations. If dose adjustment is necessary, it can be done at the first administration of the drug or during the first weeks or months of treatment.

Reactions at the injection site

As with treatment with other insulin drugs, reactions may develop at the injection site, manifested by pain, redness, urticaria, inflammation, hematoma, swelling and itching. Regularly changing injection sites in the same anatomical area may reduce symptoms or prevent reactions. In very rare cases, it may be necessary to discontinue NovoRapid® FlexPen®.

Simultaneous use of drugs of the thiazolidinedione group and insulin drugs

Cases of the development of chronic heart failure have been reported when patients were treated with thiazolidinediones in combination with insulin preparations, especially if such patients have risk factors for the development of chronic heart failure. This fact should be taken into account when prescribing combination therapy with thiazolidinediones and insulin drugs to patients. When prescribing such combination therapy, it is necessary to conduct medical examinations of patients to identify signs and symptoms of chronic heart failure, weight gain and the presence of edema. If patients' symptoms of heart failure worsen, treatment with thiazolidinediones should be discontinued.

Precautions for use

NovoRapid® FlexPen® and needles are intended for individual use only. The pen cartridge must not be refilled. NovoRapid® FlexPen® cannot be used if it is no longer transparent and colorless, or if it has been frozen. Inform the patient to discard the needle after each injection.

NovoRapid® can be used in insulin pumps (see “Dosage and Administration”). Tubing with an internal surface made of polyethylene or polyolefin has been tested and found suitable for use in pumps.

In emergency cases (hospitalization, malfunction of the insulin administration device), NovoRapid® can be removed from FlexPen® for administration to the patient using a U100 insulin syringe.

Instructions for patients on the use of NovoRapid® FlexPen®

Do not use NovoRapid® FlexPen®:

— If you have an allergy (hypersensitivity) to insulin aspart or any other component of NovoRapid®.

- If you experience hypoglycemia (low blood sugar).

— If FlexPen® has been dropped, damaged or crushed.

— If the storage conditions of the drug were violated or it was frozen.

- If insulin is no longer transparent and colorless.

Before using NovoRapid® FlexPen®:

— Check the label to make sure the correct type of insulin is selected.

- Always use a new needle for each injection to prevent infection.

— NovoRapid® FlexPen® and needles are intended for individual use only.

Mode of application

NovoRapid® is intended for subcutaneous injections or continuous infusions in an insulin pump system (PPII). NovoRapid® can also be used intravenously under strict medical supervision. Never inject insulin intramuscularly.

Change the injection site within the anatomical area each time. This will help reduce the risk of lumps and ulcerations at the injection site. It is best to inject the drug into the anterior abdominal wall, shoulder or anterior thigh. Insulin will act faster if it is injected into the anterior abdominal wall. Check your blood glucose levels regularly.

How to use NovoRapid® FlexPen®

Carefully read the attached Patient Instructions for using NovoRapid® FlexPen®.

Use your pen in strict accordance with these instructions.

Instructions for patients on the use of
NovoRapid® FlexPen®
Read these instructions carefully before using NovoRapid® FlexPen®.

NovoRapid® FlexPen® is a unique insulin syringe pen with a dispenser and color coding. The administered dose of insulin, ranging from 1 to 60 units, can be changed in increments of 1 unit. NovoRapid® FlexPen® is designed for use with disposable NovoFine® and NovoTwist® needles up to 8 mm in length. As a precaution, always carry a spare insulin delivery system with you in case your NovoRapid® FlexPen® is lost or damaged (see Figures 1, 2).

Getting Started

Check the label to make sure NovoRapid® FlexPen® contains the correct type of insulin.

A. Remove the cap from the syringe pen.

B. Remove the protective sticker from the new disposable needle. Carefully and tightly screw the needle onto NovoRapid® FlexPen®.

C. Remove the outer cap from the needle, but do not throw it away.

D. Remove and discard the inner needle cap.

— Use a new needle for each injection to prevent infection.

- Be careful not to bend or damage the needle before use.

— To avoid accidental needle sticks, never put the inner cap back on the needle.

Checking insulin delivery

Even with proper use of the pen, a small amount of air may accumulate in the cartridge before each injection.

To prevent air bubbles from entering and ensure the correct dose is administered:

E. Dial 2 units of the drug by turning the dosage selector.

F. Holding NovoRapid® FlexPen® with the needle facing up, lightly tap the cartridge several times with your fingertip so that air bubbles move to the top of the cartridge.

G. While holding NovoRapid® FlexPen® with the needle up, press the start button all the way.

The dosage selector will return to zero.

A drop of insulin should appear at the end of the needle. If this does not happen, replace the needle and repeat the procedure, but no more than 6 times.

If insulin does not come out of the needle, this indicates that the pen is faulty and cannot be used further.

Setting the dose

Make sure the dosage selector is set to the "O" position.

H. Draw the number of units required for injection.

The dose can be adjusted by rotating the dosage selector in any direction until the correct dose is set against the dosage indicator. When rotating the dosage selector, be careful not to accidentally press the trigger button to avoid releasing the insulin dose.

It is not possible to set a dose greater than the number of units remaining in the cartridge.

— You cannot use the remainder scale to measure your insulin dose.

Insulin administration

Insert the needle under the skin. Use the injection technique recommended by your doctor.

I. To inject, press the trigger button all the way until an “O” appears next to the dosage indicator. Be careful: when administering the drug, you should only press the start button.

When turning the dosage selector, the dose will not be administered.

J. While removing the needle from under the skin, keep the trigger button pressed fully.

After injection, leave the needle under the skin for at least 6 seconds. This will ensure that the full dose of insulin is administered.

K. Guide the needle into the outer needle cap without touching the cap. When the needle goes in, put on the cap and unscrew the needle (see pictures A-K).

Discard the needle, observing safety precautions, and close the syringe pen with the cap.

— Remove the needle after each injection and never store NovoRapid® FlexPen® with the needle attached. Otherwise, liquid may leak out of NovoRapid® FlexPen®, which may lead to incorrect dosage.

— Caregivers should use caution when removing and disposing of needles to avoid the risk of accidental needlestick injury.

— Throw away used NovoRapid® FlexPen® with the needle disconnected.

— Needles and NovoRapid® FlexPen® are intended for individual use only.

Storage and care

NovoRapid® FlexPen® is designed for effective and safe use and requires careful handling. In the event of a fall or strong mechanical impact, the syringe pen may be damaged and insulin may leak. The surface of NovoRapid® FlexPen® can be cleaned with a cotton swab soaked in alcohol. Do not immerse the pen in liquid, do not wash or lubricate it, because this may damage the mechanism.

Refilling NovoRapid® FlexPen® is not allowed.

Use of the drug Novorapid Flexpen

Doses. The dosage of NovoRapid FlexPen is individual and determined by the doctor in accordance with the characteristics and needs of the patient. Typically, NovoRapid FlexPen is used in combination with intermediate-acting or long-acting insulin preparations, which are administered at least once a day. The individual insulin requirement is usually 0.5–1.0 U/kg/day. With a frequency of use in accordance with food intake, 50–70% of the insulin requirement is met by NovoRapid FlexPen, and the rest by intermediate-acting or long-acting insulins. The method of administration of NovoRapid FlexPen is characterized by a faster onset and shorter duration of action compared to soluble human insulin. Due to the faster onset of action, NovoRapid FlexPen should usually be administered immediately before meals. If necessary, this drug can be administered soon after meals. NovoRapid is injected under the skin of the anterior abdominal wall, thigh, in the area of the deltoid muscle of the shoulder or buttocks. Injection sites should be changed even within the same area of the body. With subcutaneous injections in the area of the anterior abdominal wall, the effect of the drug begins within 10–20 minutes. The maximum effect is between 1-3 hours after injection. Duration of action is 3–5 hours. As with all insulins, subcutaneous injection into the anterior abdominal wall ensures faster absorption than when administered to other sites. However, the faster onset of action of NovoRapid FlexPen, compared to soluble human insulin, remains regardless of the site of administration. If necessary, NovoRapid FlexPen can be administered intravenously; these injections can only be performed under the supervision of a physician. NovoRapid can be used for continuous subcutaneous administration using appropriate infusion pumps. Continuous subcutaneous injection is carried out into the anterior abdominal wall; the injection sites should be changed periodically. When used in infusion pumps, NovoRapid should not be mixed with any other insulin preparations. Patients using infusion pumps should receive detailed instruction in the use of these systems and use the appropriate containers and tubing. The infusion set (tubes and cannulas) should be changed in accordance with the requirements of the attached instructions. Patients using NovoRapid in a pump system must have insulin in case of pump failure. Impaired liver and kidney function can reduce the patient's need for insulin. Instead of soluble human insulin, NovoRapid FlexPen should be administered to children in cases where it is desirable to obtain rapid insulin action, for example, before meals. NovoRapid FlexPen is a pre-filled pen designed for use with NovoFine® short cap needles. The package with NovoFine® needles is marked with the symbol S. FlexPen allows you to administer from 1 to 60 units of the drug with an accuracy of 1 unit. It is necessary to follow the instructions for medical use of the drug, which are in the package. NovoRapid FlexPen is intended for individual use only and cannot be reused. Instructions for use of the drug NovoRapid FlexPen NovoRapid is intended for subcutaneous injection or continuous administration using infusion pumps. NovoRapid can also be administered intravenously under the strict supervision of a physician. Use in infusion pumps For infusion pumps, tubes are used whose inner surface is made of polyethylene or polyolefin. Some insulin is initially absorbed on the inner surface of the infusion container. Use for intravenous administration Infusion systems with the drug NovoRapid 100 U/ml at a concentration of insulin aspart from 0.05 to 1.0 U/ml in an infusion solution containing 0.9% sodium chloride, 5 or 10% dextrose and 40 mmol/l potassium chloride, are in polypropylene infusion containers, are stable at room temperature for 24 hours. During the insulin infusion, it is necessary to monitor the concentration of glucose in the blood. Instructions for using the drug NovoRapid FlexPen for a patient Before using the drug NovoRapid FlexPen, check the label to see if the type of insulin you are using is correct. Always use a new needle for each injection to avoid infection. Do not use the pen: if the FlexPen pen has been dropped, damaged or deformed, as in these cases insulin may leak. If the syringe pen was stored incorrectly or was frozen. If the insulin solution does not appear clear or colorless. To avoid the formation of infiltrates, injection sites should be constantly changed. The best places for injection are the anterior abdominal wall, buttocks, anterior thigh or shoulder. Insulin works faster when injected into the waist area. How to administer this insulin preparation: Insulin should be injected under the skin, following the doctor's recommendations or the instructions for using the syringe pen.

A country

Russia
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.

Active substance

Insulin aspart

Compound

Syringe pen 3 ml Insulin aspart 100 units per 1 ml. Excipients: glycerin, phenol, metacresol, zinc chloride, sodium chloride, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, water for injection.

pharmachologic effect

A hypoglycemic drug, an analogue of human short-acting insulin, produced by recombinant DNA biotechnology using a strain of Saccharomyces cerevisiae, in which the amino acid proline at position B28 is replaced by aspartic acid. Interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase). The decrease in glucose content in the blood is due to an increase in its intracellular transport, increased uptake by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver. Substitution of the amino acid proline at position B28 with aspartic acid in the NovoRapid FlexPen drug reduces the tendency of molecules to form hexamers, which is observed in solution regular insulin. In this regard, NovoRapid FlexPen is absorbed much more quickly from subcutaneous fat and begins to act much faster than soluble human insulin. NovoRapid FlexPen lowers blood glucose levels more strongly in the first 4 hours after a meal than soluble human insulin. In patients with type 1 diabetes mellitus, lower postprandial blood glucose levels are detected when NovoRapid is administered compared to soluble human insulin. The duration of action of NovoRapid FlexPen after subcutaneous administration is shorter than that of soluble human insulin. After subcutaneous administration, the effect of the drug begins within 10-20 minutes after administration. The maximum effect is observed 1-3 hours after injection. The duration of action of the drug is 3-5 hours. When using NovoRapida FlexPen in patients with type 1 diabetes, there is a decrease in the risk of nocturnal hypoglycemia compared to soluble human insulin. There is no significant increase in the risk of daytime hypoglycemia. NovoRapid FlexPen is equipotential to soluble human insulin based on molarity indicators.

Indications for use

– diabetes mellitus type 1 (insulin dependent); – type 2 diabetes mellitus (non-insulin dependent): stage of resistance to oral hypoglycemic agents, partial resistance to these drugs (during combination therapy), intercurrent diseases.

Mode of application

NovoRapid FlexPen is intended for subcutaneous and intravenous administration. NovoRapid FlexPen has a faster onset and shorter duration of action than soluble human insulin. Due to the faster onset of action, NovoRapid FlexPen should be administered, as a rule, immediately before a meal (if necessary, it can be administered soon after a meal). The dose of the drug is determined by the doctor individually in each case, based on the level of glucose in the blood. NovoRapid FlexPen is usually used in combination with intermediate-acting or long-acting insulin preparations, which are administered at least once a day. Typically, the total daily need for insulin ranges from 0.5-1 U/kg body weight. When administering the drug before meals, the need for insulin can be met by NovoRapid FlexPen by 50-70%, the remaining need for insulin is provided by long-acting insulin. The temperature of the administered insulin should be at room temperature. NovoRapid FlexPen is injected subcutaneously into the area of the anterior abdominal wall, thigh, shoulder or buttocks. Injection sites within the same area of the body must be changed regularly. As with any other insulin preparations, the duration of action of NovoRapid FlexPen depends on the dose, injection site, blood flow intensity, temperature and level of physical activity. Subcutaneous injection into the anterior abdominal wall provides faster absorption compared to administration to other sites. However, the faster onset of action compared to soluble human insulin remains regardless of the location of the injection site. If necessary, NovoRapid FlexPen can be administered intravenously, but only by qualified medical personnel. For intravenous administration, infusion systems with the drug NovoRapid 100 units are used. ml with a concentration of 0.05 U/ml to 1 U/ml insulin aspart in 0.9% sodium chloride solution; 5% or 10% dextrose solution containing 40 mmol/L potassium chloride, using polypropylene infusion bags. These solutions are stable at room temperature for 24 hours. Blood glucose levels must be constantly monitored during insulin infusions. NovoRapid can also be used for continuous subcutaneous insulin infusions (CSII) in insulin pumps designed for insulin infusions. CSII should be administered into the anterior abdominal wall. Infusion sites should be changed periodically. When using an insulin infusion pump, NovoRapid FlexPen should not be mixed with other types of insulin. Patients using CSII must be fully trained in the use of the pump, associated reservoir, and pump tubing. The infusion set (tubing and catheter) should be replaced in accordance with the user manual supplied with the infusion set. Patients receiving NovoRapid FlexPen using CSII should have additional insulin available in case of infusion system failure.

Interaction

The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, octreotide, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, drugs lithium, drugs containing ethanol. The hypoglycemic effect of insulin is weakened by oral contraceptives, corticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine. Under the influence of reserpine and salicylates, it is possible both weakening and enhancing the effect of the drug. Pharmaceutical incompatibility Medicines containing thiol or sulfite, when added to insulin, cause its destruction.

Side effect

Side effects associated with the effect on carbohydrate metabolism: hypoglycemia (increased sweating, pale skin, nervousness or tremor, anxiety, unusual fatigue or weakness, disorientation, impaired concentration, dizziness, severe hunger, temporary blurred vision, headache , nausea, tachycardia). Severe hypoglycemia can lead to loss of consciousness and/or convulsions, temporary or irreversible disruption of brain function and death. The incidence of side effects was defined as: infrequent (&>1/1000, &1/10000, &Allergic reactions: infrequently - urticaria, skin rash; very rarely - anaphylactic reactions. Generalized allergic reactions may include skin rash, skin itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, decreased blood pressure. Local reactions: allergic local reactions (redness, swelling, itching skin at the injection site), usually temporary and passing as treatment continues; infrequently - lipodystrophy. Other: at the beginning of therapy, rarely - edema, infrequently - refractive error. These side effects are usually temporary. Adverse reactions observed in patients using the drug NovoRapid FlexPen are mainly dose-dependent and are due to the pharmacological effect of insulin.

Contraindications

- hypoglycemia; - increased individual sensitivity to insulin aspart or any of the components of the drug. It is not recommended to use NovoRapid Penfill in children under 6 years of age, because clinical studies have not been conducted in this age group. Use during pregnancy and lactation Clinical experience with the use of NovoRapid FlexPen during pregnancy is very limited. Experimental animal studies have shown no differences between the embryotoxicity and teratogenicity of insulin aspart and human insulin. During the period of possible pregnancy and throughout its entire duration, it is necessary to carefully monitor the condition of patients suffering from diabetes mellitus and monitor blood glucose levels. The need for insulin, as a rule, decreases in the first trimester and gradually increases in the second and third trimesters of pregnancy. During and immediately after childbirth, the need for insulin may decrease dramatically. Soon after birth, the need for insulin quickly returns to the level that was before pregnancy. During lactation (breastfeeding), NovoRapid FlexPen can be used without restrictions (administration of insulin to a nursing mother does not pose a threat to the child). However, it may be necessary to adjust the dose of the drug.

Overdose

Symptoms: hypoglycemia. Treatment: the patient can eliminate mild hypoglycemia on his own by ingesting glucose, sugar or carbohydrate-rich foods (patients are advised to carry sugar, sweets, cookies or sweet fruit juice with them at all times). In severe cases, when the patient loses consciousness, a 40% dextrose (glucose) solution is administered intravenously; IM or SC - glucagon (0.5-1 mg). After regaining consciousness, the patient is advised to eat a meal rich in carbohydrates to prevent the recurrence of hypoglycemia.

special instructions

Insufficient dosage of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia or diabetic ketoacidosis. Typically, symptoms of hyperglycemia appear gradually over several hours or days. Symptoms of hyperglycemia include nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, increased urine output, thirst and loss of appetite, as well as the smell of acetone in the exhaled air. Without appropriate treatment, hyperglycemia can lead to death. After compensation of carbohydrate metabolism, for example, with intensified insulin therapy, patients may experience changes in their typical symptoms that are precursors of hypoglycemia, about which patients should be informed. In patients with diabetes mellitus, with optimal metabolic control, late complications of diabetes develop later and progress more slowly. In this regard, it is recommended to carry out measures aimed at optimizing metabolic control, including monitoring blood glucose levels. A consequence of the pharmacodynamic properties of short-acting insulin analogues is that the development of hypoglycemia with their use begins earlier than with the use of soluble human insulin. NovoRapid FlexPen should apply in direct connection with food intake. The high rate of onset of the drug's effect should be taken into account when treating patients with concomitant diseases or taking medications that slow down the absorption of food. In the presence of concomitant diseases, especially of an infectious nature, the need for insulin, as a rule, increases. Impaired kidney or liver function may lead to a decrease in insulin requirements. When switching a patient to other types of insulin, early warning symptoms of hypoglycemia may change or become less severe compared to those when using the previous type of insulin. Transferring a patient to a new type of insulin or drug Use of insulin from another manufacturer must be carried out under strict medical supervision. If the concentration, type, manufacturer and type (human insulin, animal insulin, human insulin analogue) of insulin preparations and/or manufacturing method change, the dose may need to be changed. Patients switching to treatment with NovoRapid FlexPen may require an increase in the frequency of injections or a dose change compared to the doses of previously used insulin preparations. If it is necessary to adjust the dose, it can be done already at the first administration of the drug or during the first weeks or months of treatment. In addition, changing the dose of the drug may be necessary when changing the diet and with increased physical activity. Exercise performed immediately after eating may increase the risk of hypoglycemia. Skipping meals or unplanned exercise can lead to the development of hypoglycemia. Significant improvement in carbohydrate metabolism compensation can lead to a state of acute painful neuropathy, which is usually reversible. Long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy. However, intensification of insulin therapy with a sharp improvement in glycemic control may be accompanied by a temporary worsening of diabetic retinopathy. NovoRapid FlexPen contains metacresol, which in rare cases can cause allergic reactions. Use in pediatrics NovoRapid FlexPen should be used instead of soluble human insulin in children only when rapid onset is necessary effects of the drug, for example, when it is difficult for a child to maintain the required time interval between injection and meal. Effect on the ability to drive vehicles and operate machinery. Patients' ability to concentrate and reaction speed may be impaired during hypoglycemia and hyperglycemia, which can be dangerous in those situations when these abilities are especially necessary (for example, when driving a car or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia when driving a car and working with machinery. This is especially important for patients with no or decreased severity of symptoms that are warning signs of developing hypoglycemia or who suffer from frequent episodes of hypoglycemia. In these cases, the feasibility of performing such work should be considered.

Dispensing conditions in pharmacies

On prescription

Side effects of the drug Novorapid Flexpen

Adverse reactions observed in patients using NovoRapid FlexPen are mainly associated with the size of the administered dose of the drug and are a manifestation of the pharmacological action of insulin. The most commonly reported side effect of insulin therapy is hypoglycemia. It can develop if the dose significantly exceeds the patient's need for insulin. Severe hypoglycemia can lead to loss of consciousness and/or seizures, followed by temporary or permanent impairment of brain function and even death. According to the results of clinical studies, as well as data recorded after the drug was marketed, the incidence of severe hypoglycemia varies in different patient groups and with different dosage regimens; The incidence of severe hypoglycemia in patients receiving insulin aspart is the same as in patients receiving human insulin. Below is the frequency of adverse reactions that, according to clinical studies, may be associated with the administration of NovoRapid. Based on the frequency of occurrence, these reactions are divided into those that occur sometimes (1/1000, ≤1/100) and rarely (1/10,000, ≤1/1000). Individual spontaneous cases were classified as very rare (≤1/10,000). From the immune system : Sometimes: urticaria, itching, skin rashes. Very rare: anaphylactic reactions. Generalized hypersensitivity reactions may include skin rashes, itching, sweating, gastrointestinal disturbances, angioedema, difficulty breathing, palpitations and decreased blood pressure. These reactions are potentially life-threatening. From the nervous system. Rarely: peripheral neuropathies. Rapid improvement in blood glucose control may cause acute painful neuropathy, usually transient. Visual disturbances : Sometimes: refractive errors; diabetic retinopathy. Transient refractive errors may occur at the beginning of insulin therapy. Long-term maintenance of glycemic control reduces the risk of progression of diabetic retinopathy. However, intensifying insulin therapy to rapidly improve glycemic control may cause a temporary exacerbation of diabetic retinopathy. From the skin and subcutaneous tissue Sometimes : lipodystrophies can occur at injection sites as a result of non-compliance with the recommendation to change the site of drug administration within the same area; local hypersensitivity. When administering insulin, reactions at injection sites are sometimes noted as manifestations of local hypersensitivity (redness, swelling and itching). These reactions are usually transient and disappear with continued treatment. General disorders and reactions at injection sites Sometimes: swelling may develop at the beginning of insulin therapy. These symptoms are usually temporary.

NovoRapid® FlexPen® (NovoRapid® FlexPen®)

Doses

The dose of NovoRapid® FlexPen® is determined by the doctor individually according to the patient’s needs. Typically, the drug is used in combination with intermediate-acting or long-acting insulin preparations, which are administered at least once a day.

In addition, NovoRapid® FlexPen® can be used for continuous subcutaneous insulin infusions (CSII) in insulin pumps or administered intravenously by medical personnel. To achieve optimal glycemic control, it is recommended to regularly measure blood glucose concentrations and adjust the insulin dose.

Typically, the individual daily requirement for insulin in adults and children is from 0.5 to 1 U/kg body weight.

Injection therapy:

With a basal-bolus therapy regimen, the need for insulin can be met by NovoRapid® FlexPen® by 50-70%, and the remaining need (30-50%) for insulin is provided with intermediate-acting or long-acting insulin.

Continuous subcutaneous insulin infusions (CSII):

The drug NovoRapid® FlexPen® can be used for CSII in insulin pumps only in the form of monotherapy. In this case, the drug NovoRapid® FlexPen® will provide the need for both bolus (50-70%) and basal insulin (30-50%). Increased physical activity of the patient, changes in habitual diet or concomitant diseases may lead to the need for dose adjustment.

NovoRapid® FlexPen® has a faster onset and shorter duration of action than soluble human insulin.

Due to the shorter duration of action compared to human insulin, there is a risk of nocturnal hypoglycemia in patients receiving NovoRapid® FlexPen®. below.

Special patient groups

As with other insulin preparations, in elderly patients and patients with renal or hepatic insufficiency, blood glucose concentrations should be more carefully monitored and the dose of insulin aspart adjusted individually. Children and teenagers

It is preferable to use NovoRapid® FlexPen® instead of soluble human insulin in adolescents and children over 1 year of age when a rapid onset of action of the drug is necessary, for example, when it is difficult for a child to maintain the required time interval between injection and food intake (see section Pharmacological properties) .

The safety and effectiveness of NovoRapid® FlexPen® in children under 1 year of age have not been studied. No data available.

Transfer from other insulin preparations

When transferring a patient from other insulin preparations to NovoRapid® FlexPen®, it may be necessary to adjust the dose of NovoRapid® FlexPen® and basal insulin.

Mode of application

The drug NovoRapid® FlexPen® is a fast-acting analogue of insulin.

The drug NovoRapid® FlexPen® is injected subcutaneously into the anterior abdominal wall, thigh, shoulder, deltoid or buttock area. You should constantly change injection sites within the same anatomical area to reduce the risk of developing lipodystrophy. As with all insulin preparations, subcutaneous injection into the anterior abdominal wall provides faster absorption compared to injection into other areas.

The duration of action depends on the dose, site of administration, intensity of blood flow, temperature and level of physical activity. However, the faster onset of action compared to soluble human insulin persists regardless of injection site location.

Due to its faster onset of action, NovoRapid® FlexPen® should be administered, as a rule, immediately before a meal; if necessary, it can be administered soon after a meal.

Continuous subcutaneous insulin infusions (CSII):

NovoRapid® FlexPen® can be used for CSII in insulin pumps designed for insulin infusions. CSII should be administered into the anterior abdominal wall. Infusion sites should be changed periodically.

When using an insulin pump for subcutaneous infusions, NovoRapid® FlexPen® should not be mixed with other medications.

Intravenous administration:

If necessary. NovoRapid® FlexPen® can be administered intravenously, but only by qualified medical personnel.

For intravenous administration, infusion systems with the drug NovoRapid® FlexPen® 100 U/ml are used with a concentration of 0.05 U/ml to 1 U/ml insulin aspart in a 0.9% sodium chloride solution; 5% dextrose solution or 10% dextrose solution containing 40 mmol/L potassium chloride, using polypropylene infusion containers. These solutions are stable at room temperature for 24 hours.

Although stable over time, a certain amount of insulin is initially absorbed by the infusion set material. During insulin infusions, blood glucose concentrations must be constantly monitored.

Mixing two types of insulin:

NovoRapid® FlexPen® can only be mixed with isophane insulin in a syringe for subcutaneous administration. If NovoRapid® FlexPen® is mixed with isophane insulin. then first of all you should draw NovoRapid® FlexPen® into the syringe. The mixture should be used immediately after mixing. Insulin mixtures should not be administered intravenously or used for subcutaneous infusion in insulin pumps.

Directions for use of the drug

The pre-filled NovoRapid® FlexPen® pen is designed for use with NovoFine® or NovoTwist® disposable needles up to 8 mm in length. NovoRapid® FlexPen® allows you to administer doses from 1 to 60 units in 1 unit increments.

The FlexPen® syringe pen is color coded. It comes with detailed instructions for use.

NovoRapid® FlexPen® is intended for individual use only. The pen cartridge must not be refilled.

Do not use NovoRapid® FlexPen® if the solution is no longer transparent and colorless.

NovoRapid® FlexPen® should not be used if it has been frozen.

The patient should be advised to discard the needle after each injection.

In emergency cases (hospitalization, malfunction of the insulin administration device), the NovoRapid® drug for administration to the patient can be removed from the pen cartridge using the U100 insulin syringe.

Special instructions for the use of Novorapid Flexpen

Inadequate dosing or discontinuation of treatment (especially in type 1 diabetes mellitus) can lead to hyperglycemia and diabetic ketoacidosis, which are potentially fatal. Patients who have significantly improved blood glucose control, for example through intensive care, may notice a change in the usual symptoms that are warning signs of hypoglycemia, which patients should be warned about in advance. A consequence of the pharmacodynamics of fast-acting insulin analogues is the possible faster development of hypoglycemia compared to soluble human insulin. NovoRapid FlexPen should be administered immediately before meals. The rapid onset of its action should be taken into account when treating patients with concomitant diseases or taking drugs that slow down the absorption of food in the gastrointestinal tract. Concomitant illnesses, especially infections and fevers, usually increase the patient's need for insulin. The transfer of patients to a new type or type of insulin should be carried out under strict medical supervision. If the concentration, type, type, origin of the insulin preparation (animal, human, analogue of human insulin) and/or the method of its production change, it may be necessary to adjust the dose. Patients taking NovoRapid FlexPen may need an increase in the number of injections or a dose change compared to usually used insulin. The need to adjust the dose may arise both when a new drug is first introduced and during the first few weeks or months of its use. Skipping meals or unexpected intense physical activity can lead to hypoglycemia. Exercising immediately after eating increases the risk of hypoglycemia. NovoRapid FlexPen contains metacresol, which in rare cases can cause allergic reactions. Use during pregnancy and lactation Novorapid (insulin aspartate) can be used during pregnancy. According to 2 randomized controlled clinical trials (157 and 14 pregnant women treated with insulin aspart, respectively), there was no negative effect of insulin aspart on the pregnant woman or fetus/newborn compared with human insulin. Careful monitoring and monitoring of blood glucose levels should be carried out in pregnant women with diabetes (type I or II diabetes, gestational diabetes) throughout pregnancy, as well as in women planning pregnancy. Insulin requirements usually decrease in the first trimester of pregnancy and increase in the second and third trimesters. After childbirth, insulin requirements quickly return to pre-pregnancy levels. There are no restrictions on the treatment of diabetes with Novorapid during breastfeeding. Treatment of a nursing mother does not pose a risk to the baby. However, it may be necessary to adjust the dose of Novorapid. Impact on the ability to drive vehicles and machinery. The patient's responsiveness and ability to concentrate may be impaired by hypoglycemia. This may become a risk factor in situations where these abilities become particularly important (for example, when driving a car or operating machinery). Patients should be advised to take measures to prevent hypoglycemia before driving. This is especially important for patients who have mild or no symptoms - warning signs of hypoglycemia or episodes of hypoglycemia occur frequently. Under such circumstances, the advisability of driving should be weighed.

Buy NovoRapid FlexPen solution intravenously and subcutaneously 100 units/ml 3ml No. 5 in pharmacies

Instructions for use NovoRapid FlexPen solution IV and SC 100 U/ml 3ml No. 5

Dosage forms injection solution 100U/ml 3ml Synonyms NovoRapid Penfil Group Short-acting insulins International nonproprietary name Insulin aspart Composition Active substance - insulin aspart. Manufacturers Novo Nordisk A/S (Denmark), Novo Nordisk A/S, packer Novo Nordisk LLC (Denmark) Pharmacological action Hypoglycemic drug, an analogue of short-acting human insulin, produced by recombinant DNA biotechnology using the Saccharomyces cerevisiae strain The decrease in blood glucose is caused by increasing its intracellular transport, enhancing tissue uptake, stimulating lipogenesis, glycogenogenesis, reducing the rate of glucose production by the liver. Insulin aspart is absorbed much more quickly from subcutaneous fat and begins to act faster than soluble human insulin; it also lowers blood glucose levels more strongly in the first 4 hours after a meal than soluble human insulin. After subcutaneous administration, the effect of the drug begins within 10-20 minutes after administration. The maximum effect is observed 1-3 hours after injection. The duration of action of the drug is 3-5 hours. Insulin concentration returns to the original level 4-6 hours after administration of the drug. Side effects Side effects associated with the effect on carbohydrate metabolism: hypoglycemia (increased sweating, pale skin, nervousness or tremors, anxiety, unusual fatigue or weakness, disorientation, impaired concentration, dizziness, severe hunger, temporary visual impairment, headache, nausea, tachycardia). Severe hypoglycemia can lead to loss of consciousness and/or seizures, temporary or permanent impairment of brain function, and death. Allergic reactions: urticaria, skin rash, anaphylactic reactions. Generalized allergic reactions may include skin rash, itchy skin, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, and decreased blood pressure. Local reactions: allergic local reactions (redness, swelling, itching of the skin at the injection site), usually temporary and passing as treatment continues, lipodystrophy. Other: edema, refractive error. These side effects are usually temporary. Indications for use : type 1 diabetes mellitus (insulin dependent); — diabetes mellitus type 2 (non-insulin dependent): stage of resistance to oral hypoglycemic agents, partial resistance to these drugs (during combination therapy), intercurrent diseases. Contraindications - hypoglycemia; - increased individual sensitivity to insulin aspart or any of the components of the drug. It is not recommended to use insulin aspart in children under 6 years of age. Pregnancy and lactation During the possible onset of pregnancy and throughout its entire period, it is necessary to carefully monitor the condition of patients suffering from diabetes mellitus and monitor blood glucose levels. During lactation (breastfeeding), insulin aspart can be used without restrictions. Overdose Symptoms: hypoglycemia. Treatment: the patient can eliminate mild hypoglycemia on his own by ingesting glucose, sugar or carbohydrate-rich foods (patients are advised to carry sugar, sweets, cookies or sweet fruit juice with them at all times). In severe cases, when the patient loses consciousness, a 40% dextrose (glucose) solution is administered intravenously; IM or SC - glucagon (0.5-1 mg). After regaining consciousness, the patient is advised to eat a meal rich in carbohydrates to prevent the recurrence of hypoglycemia. Interaction The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, octreotide, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenflura min, lithium preparations , preparations containing ethanol. The hypoglycemic effect of insulin is weakened by oral contraceptives, corticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine. Under the influence of reserpine and salicylates, it is possible to both weaken and enhance the effect of the drug. Pharmaceutical incompatibility Medicines containing thiol or sulfite, when added to insulin, cause its destruction. Special instructions Insufficient dosage of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia or diabetic ketoacidosis. After compensation of carbohydrate metabolism, for example, with intensified insulin therapy, patients may experience changes in their typical symptoms that are precursors of hypoglycemia, of which patients should be informed. In patients with diabetes mellitus, with optimal metabolic control, late complications of diabetes develop later and progress more slowly. A consequence of the pharmacodynamic properties of short-acting insulin analogues is that the development of hypoglycemia with their use begins earlier than with the use of soluble human insulin. Insulin aspart should be used in direct connection with food intake. The high rate of onset of the drug's effect should be taken into account when treating patients with concomitant diseases or taking medications that slow down the absorption of food. Impaired kidney or liver function may reduce insulin requirements. When transferring a patient to other types of insulin, early symptoms that are precursors of hypoglycemia may change or become less pronounced compared to those when using the previous type of insulin. Transferring a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under strict medical supervision. Patients switching to insulin aspart treatment may require an increase in the frequency of injections or a dose change compared to the doses of previously used insulin preparations. If necessary, dose adjustment can be made already at the first administration of the drug or during the first weeks or months of treatment. In addition, a change in the dose of the drug may be required when changing the diet and with increased physical activity. Exercise performed immediately after eating may increase the risk of hypoglycemia. Skipping meals or unplanned exercise can lead to hypoglycemia. A significant improvement in carbohydrate metabolism compensation can lead to a state of acute painful neuropathy, which is usually reversible. Long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy. Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia when driving a car and working with machinery. For more detailed information, see the instructions for use.

Storage conditions List B. Unused NovoRapid FlexPen should be stored at a temperature of 2° to 8°C (in the refrigerator), but not near the freezer; do not freeze. To protect from light, store NovoRapid FlexPen with the protective cap on. It is not recommended to store NovoRapid FlexPen in the refrigerator. Store at a temperature not exceeding 30°C for 4 weeks from the start of use.

Interactions of the drug Novorapid Flexpen

A number of drugs affect glucose metabolism. Drugs that may reduce the need for insulin: oral hypoglycemic agents, octreotide, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, salicylates, alcohol, anabolic steroids, sulfonamides. Drugs that may increase the need for insulin: oral contraceptives, thiazides, corticosteroids, thyroid hormones, sympathomimetics, danazol. β-adrenergic blockers may mask symptoms of hypoglycemia. Alcohol can enhance and prolong the hypoglycemic effect of insulin. Incompatibility. Adding some drugs to insulin can cause it to inactivate, such as drugs containing thiols or sulfites.

Overdose of Novorapid Flexpen, symptoms and treatment

Although there is no specific definition of overdose for insulin, hypoglycemia may develop after its administration. In case of mild hypoglycemia, it is necessary to ingest glucose or sweet foods. Therefore, patients with diabetes are recommended to always have a few pieces of sugar or sweets with them. In case of severe hypoglycemia, when the patient is unconscious, it is necessary to administer an intramuscular or subcutaneous injection of glucagon (0.5–1 mg), which can be given by persons who have received appropriate instructions. A healthcare professional may give the patient IV glucose. Glucose should also be administered intravenously if the patient does not respond to glucagon administration within 10–15 minutes. After the patient regains consciousness, he should take carbohydrates orally to prevent relapse of hypoglycemia.

Novorapid FlexPen

Release form, composition and packaging

The solution for subcutaneous and intravenous administration is transparent, colorless.

1 ml insulin aspart 100 units*

Excipients: glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, sodium hydroxide, hydrochloric acid, water for injection.

* 1 unit corresponds to 35 mcg of anhydrous insulin aspart.

Clinical and pharmacological group: Short-acting analogue of human insulin

pharmachologic effect

Interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase). The decrease in blood glucose levels is due to an increase in its intracellular transport, increased absorption by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver.

Substitution of the amino acid proline at position B28 with aspartic acid in NovoRapid FlexPen reduces the tendency of molecules to form hexamers, which is observed in a solution of regular insulin. In this regard, NovoRapid FlexPen is absorbed much more quickly from subcutaneous fat and begins to act much faster than soluble human insulin. NovoRapid FlexPen lowers blood glucose levels more strongly in the first 4 hours after a meal than soluble human insulin.

After subcutaneous administration, the effect of the drug begins within 10-20 minutes after administration. The maximum effect is observed 1-3 hours after injection.

The duration of action of the drug is 3-5 hours.

When using NovoRapid FlexPen insulin in patients with type 1 diabetes, there is a reduction in the risk of nocturnal hypoglycemia compared to soluble human insulin. There was no significant increase in the risk of daytime hypoglycemia.

Insulin aspart is equipotential to soluble human insulin based on molarity. Clinical studies in adult patients with type 1 diabetes mellitus demonstrate lower postprandial blood glucose levels when administered with NovoRapid FlexPen compared to soluble human insulin.

The use of NovoRapid FlexPen in children showed similar results of long-term glucose control compared to soluble human insulin. A clinical study using soluble human insulin before meals and insulin aspart after meals was conducted in children aged 2 to 6 years (26 patients); and a single-dose pharmacokinetic/pharmacodynamic study was conducted in children 6–12 years of age and adolescents 13–17 years of age.

The pharmacodynamic profile of insulin aspart in children was similar to that in adult patients.

Clinical studies of the comparative safety and effectiveness of insulin aspart and human insulin in the treatment of pregnant women with type 1 diabetes mellitus (322 + 27 examined: 157 received insulin aspart, 165 received human insulin) did not reveal any negative effects of insulin aspart on pregnancy or health fetus/newborn. Additional clinical studies of women with gestational diabetes mellitus treated with insulin aspart (14 patients) and human insulin (13 patients) indicate comparable safety profiles along with significant improvements in postprandial glucose control with insulin aspart treatment.

Pharmacokinetics

Suction

The rate of absorption is slightly lower in patients with type 2 diabetes mellitus, resulting in a lower Cmax (352 ± 240 pmol/l) and a later Tmax (60 min).

Interindividual variability in Tmax is significantly lower with insulin aspart compared to soluble human insulin, while the reported variability in Cmax is greater for insulin aspart.

Pharmacokinetics in special clinical situations

Pharmacokinetic studies have not been conducted in elderly patients or in patients with impaired renal or hepatic function.

In children 6–12 years of age and adolescents 13–17 years of age with type 1 diabetes mellitus, absorption of insulin aspart occurs rapidly in both age groups, with a Tmax similar to that in adults. However, there are differences in the Cmax value in the two age groups, which emphasizes the importance of individual selection of the drug dosage regimen.

Indications

diabetes.

Dosage regimen

The dose of the drug is determined by the doctor individually based on the level of glucose in the blood. NovoRapid FlexPen is usually used in combination with intermediate-acting or long-acting insulin preparations, which are administered at least once a day.

Typically, the total daily need for insulin ranges from 0.5-1 U/kg body weight. When the drug is administered before meals, the need for insulin can be met by NovoRapid FlexPen by 50-70%, the remaining need for insulin is provided by long-acting insulin.

The temperature of the administered insulin should be at room temperature.

NovoRapid FlexPen is injected subcutaneously into the area of the anterior abdominal wall, thigh, shoulder or buttock. Injection sites within the same area of the body must be changed regularly.

As with any other insulin preparations, the duration of action of NovoRapid FlexPen depends on the dose, injection site, blood flow intensity, temperature and level of physical activity.

Subcutaneous injection into the anterior abdominal wall provides faster absorption compared to injection into other places. However, the faster onset of action compared to soluble human insulin persists regardless of injection site location.

If necessary, NovoRapid FlexPen can be administered intravenously, but only by qualified medical personnel.

For intravenous administration, infusion systems with the drug NovoRapid FlexPen 100 U/ml with a concentration of 0.05 U/ml to 1 U/ml insulin aspart in 0.9% sodium chloride solution are used; 5% or 10% dextrose solution containing 40 mmol/L potassium chloride, using polypropylene infusion bags. These solutions are stable at room temperature for 24 hours. During insulin infusions, blood glucose levels must be constantly monitored.

NovoRapid FlexPen can also be used for continuous subcutaneous insulin infusions (CSII) in insulin pumps designed for insulin infusions. CSII should be administered into the anterior abdominal wall. Infusion sites should be changed periodically.

When using an insulin pump for infusions, NovoRapid FlexPen should not be mixed with other types of insulin.

Patients using CSII should be fully trained in the use of the pump, associated reservoir, and pump tubing. The infusion set (tubing and catheter) should be replaced according to the user manual that came with the infusion set.

Patients receiving NovoRapid FlexPen via CSII should have additional insulin available in case of infusion system failure.

NovoRapid FlexPen is a pre-filled syringe pen with a dispenser. The FlexPen syringe pen is intended for use with injection systems for administering insulin from the company with needles with a short NovoFine cap. The package with needles is marked with the symbol “S”. The FlexPen syringe pen allows you to inject from 1 to 60 units of the drug with an accuracy of 1. You must follow the exact instructions for use supplied with the device.

The FlexPen syringe pen is intended for individual use only and cannot be refilled.

Side effect

The incidence of side effects was defined as: infrequent (1/1000, 1/100), rare (1/10000, 1/1000); isolated spontaneous cases are presented as very rare and defined as 1/10,000 - including isolated cases.

Allergic reactions: uncommon - urticaria, skin rash; very rarely - anaphylactic reactions. Generalized allergic reactions may include skin rash, itchy skin, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, and decreased blood pressure.

Storage conditions for the drug Novorapid Flexpen

Shelf life - 2.5 years. The used syringe pen with NovoRapid FlexPen should not be stored in the refrigerator. The syringe pen, which is used or carried with you as a spare, should be stored for no more than 4 weeks (at a temperature not exceeding 30 ° C). An unused syringe pen with NovoRapid FlexPen should be stored in the refrigerator at a temperature of 2–8 ° C (away from the freezer). Do not freeze. To protect from light, store the pen with the cap on.

List of pharmacies where you can buy Novorapid Flexpen:

Moscow
Saint Petersburg

NovoRapid FlexPen d/v/v and subcutaneous injection 100 units/ml spr-pen 3 ml No. 5

Compound

Active substance: insulin aspart - 100 units (3.5 mg). Excipients: glycerol - 16 mg, phenol - 1.5 mg, metacresol - 1.72 mg, zinc chloride - 19.6 mcg, sodium chloride - 0.58 mg, sodium hydrogen phosphate dihydrate - 1.25 mg, sodium hydroxide 2M - about 2.2 mg, hydrochloric acid 2M - about 1.7 mg, water for injection - up to 1 ml.

Pharmacokinetics

Substitution of the amino acid proline at position B28 with aspartic acid in insulin aspart reduces the tendency of molecules to form hexamers, which is observed in a solution of soluble human insulin. In this regard, insulin aspart is absorbed much more quickly from subcutaneous fat compared to soluble human insulin.

After subcutaneous administration of insulin aspart, Tmax in blood plasma is on average 2 times less than after administration of soluble human insulin. Cmax in blood plasma averages (492±256) pmol/l and is achieved 40 minutes (interquartile range: 30–40) after subcutaneous administration of a dose of 0.15 U/kg to patients with type 1 diabetes mellitus. Insulin concentration returns to the initial level 4–6 hours after administration of the drug dose. The rate of absorption is slightly lower in patients with type 2 diabetes mellitus, resulting in a lower Cmax (352 ± 240) pmol/L and a later Tmax (60 min (interquartile range: 50–90). Intraindividual variability in Tmax is significantly lower with the use of insulin aspart compared to soluble human insulin, whereas the reported variability in Cmax for insulin aspart is greater.

Children and teenagers

The pharmacokinetic and pharmacodynamic properties of insulin aspart were studied in children (6–12 years) and adolescents (13–17 years) with type 1 diabetes mellitus. Insulin aspart was rapidly absorbed in both age groups, with a Tmax similar to that in adults. However, there are differences in Cmax in the two age groups, which emphasizes the importance of individual dosing of insulin aspart.

Elderly

The relative differences in pharmacokinetic properties between insulin aspart and soluble human insulin in elderly patients (65–83 years, mean age 70 years) with type 2 diabetes mellitus were similar to those in healthy volunteers and in younger patients with diabetes mellitus. In elderly patients, a decrease in the rate of absorption was observed, resulting in a slower Tmax (82 min (interquartile range: 60–120), while Cmax was similar to that observed in younger patients with type 2 diabetes mellitus and slightly less than in patients with diabetes mellitus diabetes type 1.

Liver failure

A single-dose pharmacokinetic study of insulin aspart was conducted in 24 patients with normal to severe liver function. In patients with hepatic impairment, the rate of absorption of insulin aspart was reduced and more variable, resulting in a slowing of Tmax from approximately 50 minutes in subjects with normal hepatic function to approximately 85 minutes in subjects with moderate to severe hepatic impairment. AUC, Cmax and total drug clearance (CL/F) were similar in subjects with reduced and normal liver function.

Kidney failure

A study was conducted on the pharmacokinetics of insulin aspart in 18 patients whose renal function ranged from normal to severely impaired. There was no clear effect of creatinine Cl on the AUC, Cmax, CL/F and Tmax of insulin aspart. Limited data have been obtained for persons with moderate to severe renal impairment. Persons with renal failure requiring dialysis were not included in the study.

Preclinical safety data

Preclinical testing did not demonstrate any hazard to humans based on generally accepted pharmacological safety, repeated use toxicity, genotoxicity and reproductive toxicity studies.

In in vitro tests, including binding to insulin and IGF-1 receptors and effects on cell growth, the properties of insulin aspart are very similar to those of human insulin. Studies have also shown that the dissociation of insulin aspart binding to the insulin receptor is equivalent to that of human insulin.

Indications for use

diabetes mellitus type 1 (insulin dependent).
diabetes mellitus type 2 (non-insulin dependent): stage of resistance to oral hypoglycemic agents, partial resistance to these drugs (during combination therapy), intercurrent diseases.

Contraindications

Hypoglycemia, increased sensitivity to insulin aspart.

Directions for use and doses

P/c, i.v.

Doses

The dose of NovoRapid® FlexPen® is determined by the doctor individually, in accordance with the patient’s needs. Typically, the drug is used in combination with intermediate-acting or long-acting insulin preparations, which are administered at least once a day.

In addition, the drug NovoRapid® FlexPen® can be used for continuous subcutaneous insulin infusions (CSII) in insulin pumps or administered intravenously by medical personnel. To achieve optimal glycemic control, it is recommended to regularly measure blood glucose concentrations and adjust the insulin dose.

Typically, the individual daily requirement for insulin in adults and children is from 0.5 to 1 U/kg.

Injection therapy. With a basal-bolus therapy regimen, the need for insulin can be met by NovoRapid® FlexPen® by 50–70%, and the remaining need (30–50%) for insulin is provided with intermediate-acting or long-acting insulin.

PPII. The drug NovoRapid® FlexPen® can be used for CSII in insulin pumps only in the form of monotherapy. In this case, NovoRapid® FlexPen® will provide the need for both bolus (50–70%) and basal insulin (30–50%). Increased physical activity of the patient, changes in habitual diet or concomitant diseases may lead to the need for dose adjustment.

NovoRapid® FlexPen® has a faster onset and shorter duration of action than soluble human insulin.

Due to the shorter duration of action compared to human insulin, the risk of developing nocturnal hypoglycemia in patients receiving NovoRapid® FlexPen® is lower.

Special patient groups

Elderly age. As with other insulin preparations, in elderly patients and patients with renal or hepatic impairment, blood glucose concentrations should be more carefully monitored and the dose of insulin aspart adjusted individually.

Children and teenagers. It is preferable to use NovoRapid® FlexPen® instead of soluble human insulin in adolescents and children over 1 year of age when a rapid onset of action of the drug is necessary, for example, when it is difficult for a child to maintain the required time interval between injection and food intake (see “Pharmacodynamics”) .

The safety and effectiveness of NovoRapid® FlexPen® in children under 1 year of age have not been studied. No data available.

Transfer from other insulin preparations. When transferring a patient from other insulin preparations to NovoRapid® FlexPen®, it may be necessary to adjust the dose of NovoRapid® FlexPen® and basal insulin.

Mode of application

The drug NovoRapid® FlexPen® is a fast-acting analogue of insulin.

The drug NovoRapid® FlexPen® is injected subcutaneously into the area of the anterior abdominal wall, thigh, shoulder, deltoid or gluteal region. Injection sites within the same anatomical area should be rotated regularly to reduce the risk of developing lipodystrophy. As with all insulin preparations, subcutaneous injection into the anterior abdominal wall provides faster absorption compared to injection into other areas.

Due to the faster onset of action, NovoRapid® FlexPen® should be administered, as a rule, immediately before a meal; if necessary, it can be administered soon after a meal.

PPII. NovoRapid® FlexPen® can be used for CSII in insulin pumps designed for insulin infusions. CSII should be administered into the anterior abdominal wall. Infusion sites should be changed periodically.

When using an insulin pump for subcutaneous infusions, NovoRapid® FlexPen® should not be mixed with other medications.

IV administration. If necessary, NovoRapid® FlexPen® can be administered intravenously, but only by qualified medical personnel.

For intravenous administration, infusion systems with the drug NovoRapid® FlexPen® 100 U/ml with a concentration of 0.05 to 1 U/ml insulin aspart in a 0.9% sodium chloride solution are used; 5% dextrose solution or 10% dextrose solution containing 40 mmol/L potassium chloride, using polypropylene infusion containers. These solutions are stable at room temperature for 24 hours.

Although stable over time, a certain amount of insulin is initially absorbed by the infusion set material. During insulin infusions, blood glucose concentrations must be constantly monitored.

Mixing two types of insulin. The drug NovoRapid® FlexPen® can only be mixed with isophane insulin in a syringe for subcutaneous administration. If NovoRapid® FlexPen® is mixed with isophane insulin, then first of all, NovoRapid® FlexPen® should be drawn into the syringe. The mixture should be used immediately after mixing. Insulin mixtures cannot be administered intravenously or used for subcutaneous infusions in insulin pumps.

Storage conditions

At a temperature of 2–8 °C (in the refrigerator).
But not near the freezer. Do not freeze. To protect from light, store the pen with the cap on. Protect from exposure to excess heat and light. When used or carried as a spare spray pen with the drug, do not store it in the refrigerator. Store at a temperature not exceeding 30 °C. Use within 4 weeks.

Keep out of the reach of children.

Best before date

2.5 years. Do not use after the expiration date stated on the package.

special instructions

Insufficient insulin dosage or discontinuation of treatment, especially in type 1 diabetes mellitus, can lead to the development of hyperglycemia or diabetic ketoacidosis. Typically, symptoms of hyperglycemia appear gradually over several hours or days. Symptoms of hyperglycemia include nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, increased urine output, thirst and loss of appetite, as well as the smell of acetone in the exhaled air. Without appropriate treatment, hyperglycemia can lead to death. After compensation of carbohydrate metabolism, for example, with intensive insulin therapy, patients may experience changes in their typical symptoms that are precursors of hypoglycemia.

In patients with diabetes mellitus, with optimal metabolic control, late complications of diabetes develop later and progress more slowly. In this regard, it is recommended to carry out measures aimed at optimizing metabolic control, including monitoring blood glucose levels.

A consequence of the pharmacodynamic properties of short-acting insulin analogues is that the development of hypoglycemia with their use begins earlier than with the use of soluble human insulin.

The high rate of development of the hypoglycemic effect should be taken into account when treating patients with concomitant diseases or taking medications that slow down the absorption of food. In the presence of concomitant diseases, especially of infectious origin, the need for insulin, as a rule, increases. Impaired kidney or liver function may reduce insulin requirements.

When transferring a patient to other types of insulin, early symptoms that are precursors of hypoglycemia may change or become less pronounced compared to those when using the previous type of insulin.

Changing the insulin dose may be necessary with changes in diet and increased physical activity. Exercise performed immediately after eating may increase the risk of hypoglycemia. Skipping meals or unplanned exercise can lead to hypoglycemia.

A significant improvement in carbohydrate metabolism compensation can lead to a state of acute painful neuropathy, which is usually reversible.

Long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy. However, intensification of insulin therapy with a sharp improvement in glycemic control may be accompanied by a temporary worsening of diabetic retinopathy.

Not recommended for use in children under 6 years of age.

Description

An analogue of human insulin with an average duration of action.

Dosage form

The solution for subcutaneous and intravenous administration is transparent, colorless.

Use in children

Not recommended for use in children under 6 years of age.

Action

In the molecular structure of this insulin, the amino acid proline at position B28 is replaced by aspartic acid, which reduces the tendency of molecules to form hexamers, which is observed in a solution of regular insulin.

Interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase). The hypoglycemic effect is associated with an increase in intracellular transport and increased absorption of glucose by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver.

Insulin aspart and human insulin have the same activity in molar equivalent.

Insulin aspart is absorbed from subcutaneous fat tissue more quickly and has a faster onset of action than soluble human insulin.

The duration of action of insulin aspart after subcutaneous administration is shorter than that of soluble human insulin.

Side effects

Allergic reactions: possible - urticaria, skin rash; rarely - anaphylactic reactions. Generalized allergic reactions may include skin rash, itchy skin, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, and decreased blood pressure.

Local reactions: allergic reactions (redness, swelling, itching of the skin at the injection site), usually temporary and passing as treatment continues; lipodystrophy is possible.

Other: at the beginning of therapy, rarely - swelling, possible refractive error.

Use during pregnancy and breastfeeding

Clinical experience with the use of insulin asprate during pregnancy is very limited.

Experimental animal studies have shown no differences between the embryotoxicity and teratogenicity of insulin aspart and human insulin. During the period of possible pregnancy and throughout its entire duration, it is necessary to carefully monitor the condition of patients suffering from diabetes mellitus and monitor blood glucose levels. The need for insulin, as a rule, decreases in the first trimester and gradually increases in the second and third trimesters of pregnancy. During and immediately after childbirth, the need for insulin may decrease dramatically. Shortly after birth, insulin requirements quickly return to pre-pregnancy levels.

Insulin asprate can be used during lactation (breastfeeding), but insulin dosage adjustment may be required.

Interaction

The hypoglycemic effect of insulin is weakened by oral contraceptives, corticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.

Under the influence of reserpine and salicylates, it is possible to both weaken and enhance the effect of the drug.

Medicines containing thiol or sulfite, when added to insulin, cause its destruction.

Overdose

Symptoms: hypoglycemia.
Treatment: the patient can eliminate mild hypoglycemia on his own by ingesting glucose, sugar or carbohydrate-rich foods (patients are advised to carry sugar, sweets, cookies or sweet fruit juice with them at all times). In severe cases, when the patient loses consciousness, a 40% dextrose (glucose) solution is administered intravenously; IM or SC - glucagon (0.5-1 mg). After regaining consciousness, the patient is advised to eat a meal rich in carbohydrates to prevent the recurrence of hypoglycemia.

Impact on the ability to drive vehicles and operate machinery

Patients' ability to concentrate and react quickly may be impaired during hypoglycemia and hyperglycemia, which can be dangerous in situations where these abilities are especially needed (for example, when driving a car or working with machinery). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia when driving a car and working with machinery. This is especially important for patients with no or decreased severity of symptoms that are warning signs of developing hypoglycemia or who suffer from frequent episodes of hypoglycemia. In these cases, the feasibility of performing such work should be considered.