Instructions Actrapid NM Flexpen solution for injection 100 IU/ml cartridge 3 ml in multidose disposable syringe pen No. 5
Composition
active ingredient: human insulin (rDNA);
1 ml of solution for injection contains 100 IU of human biosynthetic insulin (recombinant DNA produced from Saccharomyces cerevisiae);
1 IU (international unit) is equal to 0.035 mg of anhydrous human insulin;
1 multidose disposable syringe pen contains 3 ml of solution for injection, equivalent to 300 IU;
Excipients: zinc chloride, glycerin, metacresol, sodium hydroxide (for pH adjustment), diluted hydrochloric acid (for pH adjustment), water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: colorless, transparent liquid, free from foreign particles; traces of a very fine sediment may be detected during storage.
Pharmacotherapeutic group
Antidiabetic drugs. Insulins and analogues for injection, short-acting. ATC code A10A B01.
Pharmacological properties
Pharmacodynamics
The blood sugar-lowering effect of insulin consists in promoting the absorption of glucose by tissues after insulin binds to receptors on muscle and fat cells, as well as in simultaneously inhibiting the release of glucose from the liver.
Results from a single intensive care unit clinical trial in the treatment of hyperglycemia (blood glucose levels above 10 mmol/L) in 204 diabetic and 1344 non-diabetic patients undergoing major surgery showed that normoglycemia (glucose levels 4.4–6.1 mmol/L) induced by intravenous administration of the drug reduced mortality by 42% (8% versus 4.6%).
Actrapid® NM FlexPen® is a short-acting insulin preparation.
The onset of action is observed within 30 minutes, the maximum effect is achieved within 1.5–3.5 hours, and the duration of action is approximately 7–8 hours.
Pharmacokinetics
The half-life of insulin from the blood is several minutes, so the action profile of an insulin preparation is determined solely by its absorption characteristics. This process depends on a number of factors (e.g., insulin dose, method and site of injection, thickness of subcutaneous tissue, type of diabetes), which causes significant variability in the effect of an insulin preparation both in the same and in different patients.
Absorption: Peak plasma concentrations occur within 1.5–2.5 hours after subcutaneous injection.
Distribution: No significant binding of insulin to plasma proteins has been observed, except for circulating antibodies to it (if present).
Metabolism. Human insulin is cleaved by insulin proteases or insulin-degrading enzymes and possibly by protein disulfide isomerase. A number of cleavage sites (hydrolysis) of the human insulin molecule have been identified. None of the metabolites formed after hydrolysis have biological activity.
Elimination. The terminal half-life of insulin is determined by the rate of absorption from the subcutaneous tissue. Therefore, the terminal half-life (t½) indicates the rate of absorption, not the rate of elimination (as such) of insulin from the blood plasma (the t½ of insulin from the bloodstream is only a few minutes). Studies have shown that t½ is 2–5 hours.
Children and adolescents
The pharmacokinetic profile of the drug was studied in a small number (n=18) of children (6–12 years) and adolescents (13–17 years) with diabetes. Limited data suggest that the pharmacokinetic profile of insulin in children, adolescents, and adults is essentially the same. However, Cmax (maximum concentration) was different in children of different ages, indicating the importance of individual dose selection.
Preclinical safety data
In preclinical studies (repeated dose toxicity, genotoxicity, carcinogenicity, reproductive toxicity) no hazard was identified from the administration of the drug.
Indication
Diabetes treatment.
Contraindication
Hypersensitivity to human insulin or to any ingredient of the drug.
Interaction with other medicinal products and other types of interactions
As is known, a number of medications affect glucose metabolism.
Medicines that may reduce insulin requirements
Oral hypoglycemic agents (OHAs), monoamine oxidase inhibitors (MAOIs), non-selective beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, salicylates, anabolic steroids, and sulfonamides.
Medicines that may increase insulin requirements
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol; beta-blockers may mask symptoms of hypoglycaemia and delay recovery from hypoglycaemia; octreotide/lanreotide may either reduce or increase insulin requirements; alcohol may potentiate or weaken the hypoglycaemic effect of insulin.
Application features
Inadequate dosage or discontinuation of treatment (especially in type 1 diabetes) may lead to hyperglycemia. Usually the first symptoms of hyperglycemia develop gradually, over several hours or days. They include thirst, increased urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone on the exhaled air.
In type 1 diabetes, untreated hyperglycemia leads to diabetic ketoacidosis, which is potentially fatal.
Hypoglycemia can occur if the insulin dose is too high relative to the insulin requirement.
Skipping a meal or unexpectedly exercising can lead to hypoglycemia.
Patients whose blood glucose control has improved significantly due to intensive insulin therapy may experience changes in the usual symptoms that herald hypoglycemia, and they should be warned about this in advance.
The usual warning symptoms may disappear in patients with long-standing diabetes.
Transferring a patient to another type or type of insulin is carried out under strict medical supervision. Changing the concentration, type (manufacturer), type, origin of insulin (human or human insulin analogue) and/or method of production may require a correction of the insulin dose. Patients transferred to Actrapid® NM FlexPen® from another type of insulin may require an increase in the number of daily injections or a change in dosage compared to the insulin they usually used. The need for dose adjustment may arise both when the new drug is first introduced and during the first few weeks or months of its use.
Injection site reactions may occur with any insulin therapy and may include pain, redness, itching, hives, swelling, bruising and inflammation. Constantly changing the injection site within the same area may reduce or prevent these reactions. The reactions usually resolve within a few days or weeks. Rarely, injection site reactions may require discontinuation of Actrapid® NM FlexPen® treatment.
Before traveling with a change in time zones, patients should consult a doctor, as this changes the schedule of insulin injections and meals.
Actrapid® NM FlexPen® should not be used in insulin pumps for long-term subcutaneous insulin administration due to the risk of sediment formation in their tubes.
Avoiding accidental input errors.
Patients should be instructed and always check the label on the insulin package before each injection to avoid accidentally mixing Actrapid® NM FlexPen® with other insulin preparations.
Combination of thiazolidinediones and insulin preparations
Cases of congestive heart failure have been reported with thiazolidinediones in combination with insulin, especially in patients with risk factors for the development of congestive heart failure. This should be taken into account when prescribing thiazolidinediones in combination with insulin. When these drugs are used in combination, patients should be monitored for signs and symptoms of congestive heart failure, weight gain and edema. In the event of any deterioration in cardiac function, thiazolidinediones should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
The patient's reactions and ability to concentrate may be impaired during hypoglycemia. This may be a risk factor in situations where these abilities are of particular importance (e.g., when driving a car or operating other machinery).
Patients should be advised to take precautions to prevent hypoglycemia before driving. This is especially important for patients who have reduced or absent warning signs of hypoglycemia or who have frequent episodes of hypoglycemia. In such circumstances, the advisability of driving should be considered.
Use during pregnancy or breastfeeding
Since insulin does not cross the placental barrier, there are no restrictions on treating diabetes with insulin during pregnancy.
Inadequate control of diabetes can lead to both hypoglycemia and hyperglycemia, which increase the risk of fetal malformations and death. Therefore, it is recommended to increase blood glucose control and monitor the treatment of pregnant women with diabetes throughout pregnancy and when pregnancy is suspected.
Insulin requirements usually decrease in the first trimester of pregnancy and gradually increase in the second and third trimesters. After delivery, insulin requirements usually return rapidly to baseline.
There are no restrictions on the treatment of diabetes with Actrapid® NM FlexPen® during breastfeeding, as the treatment of the mother does not pose any risk to the child. However, it may be necessary to adjust the dose and diet for the mother.
Method of administration and doses
Actrapid® NM FlexPen® is a syringe pen filled with a short-acting insulin preparation, so it can be used in combination with long-acting insulin.
Dosage
The individual daily insulin requirement is usually 0.3 to 1.0 IU/kg/day. The daily insulin requirement may increase in patients with insulin resistance (e.g. during puberty or obesity) and decrease in patients with residual endogenous insulin production.
The injection should be given 30 minutes before a main or additional meal containing carbohydrates.
Dose adjustment
Concomitant diseases, especially infections and fever, usually increase the patient's insulin requirements. Concomitant diseases of the kidneys, liver, or damage to the adrenal, pituitary, or thyroid glands require a change in insulin dosage.
Dose adjustment may also be necessary when patients change their physical activity or their usual diet. Dose adjustment may also be necessary when transferring patients to other insulin preparations.
Introduction
Actrapid® NM FlexPen® is intended for subcutaneous or intravenous injections.
Subcutaneous use
Actrapid® NM FlexPen® is usually injected subcutaneously in the areas of the anterior abdominal wall, as well as the thighs, buttocks or deltoid muscle of the shoulder.
With subcutaneous injections into the anterior abdominal wall, insulin absorption occurs faster than when injected into other areas of the body.
Injecting into a retracted skin fold significantly reduces the risk of accidental injection into a muscle.
After injection, the needle should remain under the skin for at least 6 seconds. This will ensure that the full dose is administered.
To reduce the risk of lipodystrophy, injection sites should always be rotated, even within the same area of the body.
Intramuscular injections can be performed under the supervision of a physician.
Intravenous use
Intravenous administration of Actrapid® NM FlexPen® can only be performed by a healthcare professional. Intravenous administration of Actrapid® NM FlexPen® from a pen or cartridge is performed only when vials are not available. In this case, the drug should be drawn into an insulin syringe, removing air from the syringe, and the drug should be injected into the infusion system. This procedure should only be performed by a healthcare professional.
The drug cannot be used in insulin infusion pumps for long-term subcutaneous infusion due to the risk of precipitation in the pump catheter.
Infusion systems with Actrapid® HM 100 IU/ml at a concentration of human insulin from 0.05 IU/ml to 1.0 IU/ml in infusion solutions: 0.9% sodium chloride, 5% or 10% dextrose and 40 mmol/l potassium chloride, using polypropylene infusion containers are stable at room temperature for 24 hours. Some insulin may initially adsorb to the inner surface of the infusion container. During insulin infusion, it is necessary to monitor the concentration of glucose in the blood.
The FlexPen® pre-filled insulin pen is designed to be used with NovoFine® or NovoTwist® disposable needles up to 8 mm long. The FlexPen® allows you to deliver doses from 1 to 60 units in increments of 1 unit.
The instructions for use of these medical devices should be carefully followed.
Instructions for use of the drug Actrapid® NM FlexPen®
Before using your FlexPen®, you must read these instructions carefully. If you do not follow the instructions carefully enough, you may inject too little or too much insulin, which can lead to a sharp increase or decrease in your blood glucose level.
FlexPen® is a pre-filled insulin pen with a dose selector that allows you to set the dose from 1 to 60 units of insulin in increments of 1 unit. FlexPen® is used with NovoFine® or NovoTwist® needles up to 8 mm long. As a precaution, always carry a spare insulin delivery device in case your FlexPen® is damaged or lost.
Caring for your syringe pen
The FlexPen® syringe pen must be handled with care. If it is dropped, damaged or deformed, there is a risk of insulin leakage.
The surface of the FlexPen® can be cleaned by wiping it with a cotton swab. It should not be wetted, washed or lubricated as this may damage the pen.
Do not refill the pen. If it is empty, it must be disposed of.
Preparing the FlexPen® syringe pen for injection.
Check the name of the medicine and the color of the label to make sure that the pen contains the right type of insulin. This is especially important if you use more than one type of insulin. If you inject the wrong type of insulin, your blood sugar level may go too high or too low.
Caring for your syringe pen
The FlexPen® syringe pen must be handled with care. If it is dropped, damaged or deformed, there is a risk of insulin leakage.
The surface of the FlexPen® can be cleaned by wiping it with a cotton swab. It should not be wetted, washed or lubricated as this may damage the pen.
Do not refill the pen. If it is empty, it must be disposed of.
Preparing the FlexPen® syringe pen for injection.
Check the name of the medicine and the color of the label to make sure that the pen contains the right type of insulin. This is especially important if you use more than one type of insulin. If you inject the wrong type of insulin, your blood sugar level may go too high or too low.
Remove the cap from the syringe pen/
Screw the needle tightly onto the FlexPen® syringe pen.
Remove the large outer needle cap. Do not throw it away.
Remove the inner needle cap and throw it away.
Never try to put the removed inner needle cap back on, as you may get injured by the needle.
* Always use a new needle for each injection. This will reduce the risk of contamination, infection, insulin leakage, blocked needles, and inaccurate dosing.
* Be careful not to bend or damage the needle before use.
Checking insulin flow
When using the pen, a small amount of air may accumulate in the cartridge. To prevent air injection and ensure that the correct dose is administered, do the following:
Set the dose selector to 2 units.
Holding the FlexPen® vertically with the needle pointing upwards, gently tap the cartridge with your finger several times to collect any air bubbles at the top of the cartridge.
Holding the FlexPen® syringe pen vertically with the needle pointing upwards, press the start button. This will return the dose selector to the zero mark.
A drop of insulin should appear at the tip of the needle. If this does not happen, replace the needle and repeat this procedure up to 6 times.
If a drop of insulin still does not appear, this indicates that the pen is damaged and a new pen should be used.
* Before injecting, always check to see if a drop appears at the tip of the needle. This will confirm that insulin is coming through the needle. If no drop appears, you will not be able to inject any insulin, even if the dose selector moves. This indicates that the needle is blocked or damaged.
* Always check the flow of insulin through the needle before injecting. If you do not do this, you may get too little insulin or no insulin at all. This can lead to a significant increase in your blood sugar.
Dose setting
Make sure the dose selector is set to “0”
Turn the dose selector to select the number of units needed for injection.
The dose can be adjusted either up or down by turning the dose selector in the appropriate direction until the required dose lines up with the dose pointer. When turning the selector, take care not to accidentally press the injection button, as this will cause insulin to leak out.
It is not possible to dial a dose that exceeds the number of units remaining in the cartridge.
* Always use the dose selector and pointer to see how many units you have dialed before injecting insulin.
* Do not count the clicks of the pen to select the insulin dose. If you select and inject the wrong dose of insulin, your blood sugar level may rise or fall. Do not use the remaining insulin scale, as it only shows the approximate amount of insulin left in your pen.
Insulin administration
Insert the needle under the skin. Follow the injection technique taught by your doctor or nurse.
Inject the dose by pressing the injection button all the way in until “0” lines up with the dose pointer. Be careful to only press the injection button when injecting.
Turning the dose selector will not deliver insulin.
Keep the trigger button fully depressed, leaving the needle under the skin for at least 6 seconds. This ensures that the full dose of medicine is delivered.
Pull the needle out of the skin and release the trigger button.
Always make sure that the dose pointer has returned to “0” after the injection. If the dose pointer stops before it has returned to “0”, the full dose has not been injected, which may cause your blood sugar to rise.
Cover the needle with the large outer cap without touching it.
When the needle is completely covered by the large outer cap, gently press the cap down and then unscrew the needle.
Carefully dispose of the needle and put the cap back on the pen.
* Always remove the needle after each injection and store Actrapid® NM FlexPen® without a needle attached. This will reduce the risk of contamination, infection, insulin leakage, blocked needle and inaccurate dosing.
Additional important information
* Healthcare professionals, relatives, and other caregivers should be very careful with used needles to reduce the risk of accidental needlesticks and cross-infection.
* Dispose of the used syringe pen without the needle.
* Never share your pen or needle with other people. This can lead to cross-infection.
* Never share your pen with other people. Your medication may be dangerous to their health.
* Keep your pen and needles out of the reach of others, especially children.
Children
Biosynthetic human insulin preparations are effective and safe drugs for the treatment of diabetes mellitus in children and adolescents of different age groups. The daily insulin requirement in children and adolescents depends on the stage of the disease, body weight, age, diet, physical activity, degree of insulin resistance and dynamics of glycemia levels.
Overdose
Although there is no specific concept of overdose for insulin, if doses that are too high compared to the patient's needs are used, hypoglycemia may develop in successive stages after its administration.
Mild hypoglycemia can be treated by oral glucose or sugary foods. Therefore, diabetics are advised to carry several sugar-containing foods with them at all times. In the case of severe hypoglycemia, when the patient is unconscious, glucagon should be administered subcutaneously or intramuscularly (0.5 to 1.0 mg) by trained personnel. Glucose can be given intravenously by a healthcare professional. Glucose should also be given intravenously if the patient does not respond to glucagon within 10–15 minutes.
After the patient regains consciousness, he should consume foods containing carbohydrates to prevent relapse.
Adverse reactions
The most common side effect of therapy is hypoglycemia. According to clinical studies, as well as post-marketing data, the frequency of hypoglycemia varies in different patient groups, with different dosing regimens and levels of glycemic control.
At the beginning of insulin therapy, refractive errors, edema and injection site reactions (pain, redness, urticaria, inflammation, bruising, swelling and itching at the injection site) may occur. These reactions are usually transient. Rapid improvement in blood glucose control may cause acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with rapid improvement in glycemic control may cause temporary worsening of diabetic retinopathy, whereas continued good glycemic control reduces the risk of progression of diabetic retinopathy.
Based on clinical trial data, adverse reactions are listed below, classified by frequency and MedDRA system organ class.
According to the frequency of occurrence, these reactions were divided into those that occur very often (≥1/10), often (≥1/100 to <1/10), infrequently (>1/1000 to <1/100), rarely (>1/10000 to <1/1000), very rarely (<1/10000), with an unknown frequency (cannot be estimated from the available data).
Immune system disorders
Hives, itching – uncommon.
Anaphylactic reactions* are very rare.
Metabolic and nutritional disorders
Hypoglycemia* – very common.
Nervous system disorders
Peripheral neuropathies (painful neuropathies) are uncommon.
Visual impairment
Refractive errors are uncommon.
Diabetic retinopathy is very rare.
Skin and subcutaneous tissue reactions
Lipodystrophy* – uncommon.
General disorders and administration site reactions
Injection site reactions are uncommon.
Swelling is uncommon.
*– see “Selected adverse reactions”.
Certain adverse reactions
Anaphylactic reactions
Symptoms of generalised hypersensitivity (including generalised skin rash, itching, sweating, digestive disorders, angioedema, difficulty breathing, rapid heartbeat, low blood pressure and dizziness/loss of consciousness) are very rare but can be potentially life-threatening.
Hypoglycemia
The most common side effect is hypoglycemia. This can occur when the dose is significantly higher than the patient's insulin requirement. Severe hypoglycemia can lead to loss of consciousness and/or seizures, followed by temporary or permanent brain damage and even death. Symptoms of hypoglycemia usually come on suddenly. They may include cold sweat, pale and cool skin, fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, confusion, difficulty concentrating, drowsiness, excessive hunger, vision changes, headache, nausea and rapid heartbeat.
Lipodystrophy
Lipodystrophy has been reported occasionally. Lipodystrophy may develop at injection sites.
Expiration date
2.5 years.
Storage conditions
Store in the original packaging at 2°C – 8°C (in the refrigerator, not too close to the freezer compartment). Do not freeze.
Keep the pen cap closed to protect from light.
After first opening: use within 6 weeks. Do not refrigerate. Do not store above 30°C.
Keep out of reach of children.
Packaging
The drug is placed in a 3 ml cartridge made of type 1 glass, which is closed on one side with a rubber plunger made of bromobutyl rubber and on the other side with a stopper made of bromobutyl/polyisoprene rubber. The cartridge is placed in a multi-dose disposable syringe pen made of plastic.
5 syringe pens in a cardboard box.
Vacation category
According to the recipe.
Producer
Novo Nordisk A/S, Denmark.
Novo Nordisk Production SAS, France. Novo Nordisk Production SAS, France.
Location of the manufacturer and its business address
Novo Alle, 2880 Bagsvaerd, Denmark. Novo Alle, 2880 Bagsvaerd, Denmark.
45, avenue d'Orleans, 28000, Chartres, France. 45 avenue d'Orleans, 28000 Chartres, France.
