Novorapid® Flexpen® 100 units/mL, 5 syringe pens of 3 ml

Trade Name:

Novorapid® Flexpen® 100 units/mL 

5 syringe pens of 3 ml

NovoRapid® FlexPen®

Composition:

Insulin aspart- 100 units (corresponds to 3.5 mg of anhydrous insulin aspart);

Inactive ingredients: glycerol; phenol; metacresol; zinc chloride; sodium phosphate dihydrate; sodium chloride; sodium hydroxide; hydrochloric acid; water for injection.

Properties:

Solution for intravenous and subcutaneous administration in a syringe pen.

Pharmacotherapeutic group:

Hypoglycemic agent.

NovoRapid® FlexPen® is a short-acting human insulin analog produced by recombinant DNA biotechnology using Saccharomyces cerevisiae strain, in which the amino acid proline in position B28 is replaced by asparaginic acid. It interacts with a specific receptor of the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, including the synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthase, etc.).

Decrease in blood glucose content is caused by an increase in its intracellular transport, increased tissue uptake, stimulation of lipogenesis, glycogen organogenesis, decrease in the rate of glucose production by the liver, etc. The decrease in the rate of glucose production by the liver is also caused by a decrease in the rate of glucose synthesis. Substitution of the amino acid proline in position B28 with asparagic acid in NovoRapid® FlexPen® reduces the tendency of molecules to form hexamers, which is observed in the solution of regular insulin. Therefore, NovoRapid® FlexPen® is absorbed much faster from the subcutaneous fat. As a result, NovoRapid® FlexPen® is absorbed much faster from the subcutaneous fatty tissue and takes effect much faster than soluble human insulin.

NovoRapid® FlexPen® reduces blood glucose levels more strongly in the first 4 h after a meal than 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 starts within 10-20 min after administration. The maximum effect is observed 1-3 h after injection.

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

Indications:

Diabetes mellitus type 1 and 2 in adults, adolescents and children over 2 years of age.

Dosage and administration:

-Dose of NovoRapid® FlexPen® is determined by a doctor individually according to the needs of the patient. 

-The drug is usually used in combination with insulin preparations of medium duration or long-acting, which are administered at least once a day. To achieve optimal glycemic control, it is recommended to regularly measure blood glucose concentration and adjust the insulin dose. 

– Usually the individual daily requirement for insulin in adults and children is from 0.5 to 1 U/kg body weight. When the drug is administered before meals, the insulin requirement can be met with NovoRapid® FlexPen® by 50-70%, the remaining insulin requirement is met with prolonged-acting insulin.

-Increased physical activity of the patient, changes in the 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 its faster onset of action, NovoRapid® FlexPen® should generally be administered immediately before a meal; if necessary, it may be administered shortly after a meal.

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

-Special patient groups:

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

-Children and adolescents

The use of NovoRapid® FlexPen® instead of soluble human insulin in children is preferred when a rapid onset of action is required, for example, when it is difficult for the child to maintain the required time interval between injection and meal.

-Transfer from other insulin preparations

When transferring a patient from other insulin preparations to NovoRapid® FlexPen® , the dose of NovoRapid® FlexPen® and baseline insulin may need to be adjusted.

-NovoRapid® FlexPen® is injected subcutaneously into the anterior abdominal wall, thigh, upper arm, deltoid, or gluteal region. Injection sites within the same area of the body should be changed regularly to reduce the risk of lipodystrophy. As with all insulin preparations, subcutaneous injection into the anterior abdominal wall provides faster absorption than injection into other sites. The duration of action depends on dose, site of administration, blood flow, temperature, and level of physical activity. However, the faster onset of action compared to soluble human insulin is maintained regardless of the localization of the injection site.

NovoRapid® may be used for continuous subcutaneous insulin infusion (CSI) in insulin pumps designed for insulin infusion. PPIs should be given into the anterior abdominal wall. Infusion sites should be changed periodically.

-NovoRapid® should not be mixed with other types of insulin when using an insulin pump for infusion. Patients using PPII should be fully trained in the use of the pump, the appropriate reservoir, and the tubing system for the pump. The infusion set (tubing and catheter) should be replaced according to the user manual provided with the infusion set.

Patients receiving NovoRapid® with PPII should have extra insulin available in case of infusion system failure.

-Intravenous administration:

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

For intravenous administration, infusion systems are used with NovoRapid® 100 U/mL with a concentration of 0.05 U/mL to 1 U/mL of insulin aspart in 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 for some time, a certain amount of insulin is initially absorbed by the infusion system material. During insulin infusions, blood glucose concentrations should be monitored continuously.

Side effects:

-Immune system disorders:

Occasionally: urticaria, itching, rash.

Very rare: anaphylactic reactions. Symptoms of generalized hypersensitivity: skin rash, pruritus, increased sweating, GI disorders, angioedema, difficulty breathing, accelerated heart rate and decreased BP. These reactions are potentially life-threatening.

-Nervous system disorders:

Rarely: peripheral neuropathies. Rapid improvement of blood glucose control may cause a reversible state of acute painful neuropathy.

-Vision disorders:

Occasionally: refractive disorders; diabetic retinopathy. Refractive disorders of a transient nature may occur at the onset of insulin therapy.

Prolonged maintenance of good glycemic control reduces the risk of progression of diabetic retinopathy. However, intensification of insulin therapy to rapidly improve glycemic control may cause temporary exacerbation of diabetic retinopathy.

-Skin and subcutaneous tissue disorders:

Occasionally: lipodystrophies may occur at injection sites if the patient does not change the injection site within the same body region. Local hypersensitivity.

Skin reactions (pain, redness, hives, inflammation, swelling, and itching) may occur at injection sites when insulin is administered, which usually resolve with continued treatment.

-General abnormalities and reactions at injection sites:

Occasionally: swelling that may develop at the beginning of insulin therapy. This symptom usually resolves quickly. Contraindications:

-Excessive sensitivity to human insulin or any ingredient of the drug; 

-Hypoglycemia. 

Warnings and precautions:

-Drug Interactions:

The hypoglycemic effect of insulin is potentiated by oral hypoglycemic agents, MAO inhibitors, ACE inhibitors, carboanhydrase inhibitors, nonselective beta-adrenoblockers, bromocriptine, octreotide, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, preparations containing ethanol.

Hypoglycemic effect of insulin is weakened by oral contraceptives, GCS, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, calcium channel blockers, diazoxide, morphine, phenytoin, nicotine. Under the influence of reserpine and salicylates both weakening and strengthening of the drug action is possible.

-Pharmaceutical interaction. Drugs containing thiols or sulfites, when added to insulin, cause its destruction.

-Patients should consult their physician before traveling for long periods of time due to time zone changes, as a time zone change means that the patient must eat and administer insulin at a different time.

-Hyperglycemia. Inadequate drug dosage 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 a period of hours or days. Symptoms of hyperglycemia include nausea, vomiting, drowsiness, red and dry skin, dry mouth, increased urine output, thirst and loss of appetite, and the odor of acetone in exhaled air. Without appropriate treatment, hyperglycemia can lead to death.

Skipping a meal, unplanned increased physical activity, or an insulin dose that is too high relative to the patient’s need can lead to hypoglycemia. After compensation of carbohydrate metabolism, e.g. with intensified insulin therapy, the typical precursor symptoms of hypoglycemia may change and patients should be informed. The usual precursor symptoms may disappear during the long-term course of diabetes mellitus.

As a consequence of pharmacodynamic peculiarities of short-acting insulin analogs, the development of hypoglycemia during their use may start earlier than during the use of soluble human insulin.

-Since NovoRapid® FlexPen® should be administered in direct connection with food intake, it is necessary to take into account the high rate of onset of the drug effect when treating patients with concomitant diseases or taking drugs that slow down food absorption. Concomitant diseases, especially infectious and accompanied by fever, usually increase the need of the organism in insulin. Adjustment of the drug dose may also be necessary if the patient has concomitant kidney, liver, adrenal, pituitary or thyroid disorders.

-Transferring the patient from other insulin preparations. Transfer of the patient to a new type of insulin or insulin preparation of another manufacturer should be carried out under strict medical supervision. If the concentration, type, manufacturer and type (human insulin, animal insulin, human insulin analog) of insulin preparations and/or method of manufacture are changed, it may be necessary to change the dose or increase the frequency of injections compared to the previously used insulin preparations. If dose adjustments are necessary, they may be made as early as the first injection or during the first weeks or months of treatment.

-Injection site reactions. As with other insulin preparations, injection site reactions may develop, which are manifested by pain, redness, hives, inflammation, hematoma, swelling, and itching. Regularly changing the injection site in the same anatomical region may reduce symptoms or prevent the development of reactions. In very rare cases, NovoRapid® FlexPen® may need to be discontinued.

-Simultaneous use of drugs of thiazolidinedione group and insulin preparations. Cases of development of chronic heart failure have been reported in patients treated with thiazolidinediones in combination with insulin preparations, especially if such patients have risk factors for development of chronic heart failure. In case of worsening of heart failure symptoms in patients, treatment with thiazolidinediones should be discontinued.

-Effect on the ability to drive vehicles and work with mechanisms. Patients’ ability to concentrate and reaction speed may be impaired during hypoglycemia, which may be dangerous in those situations when these abilities are especially needed (e.g. when driving a vehicle or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia when driving vehicles and working with machinery. 

Storage:

Store in the refrigerator, at a temperature of 2°C-8°C. Do not freeze.

Package:

Carton box holds 5 syringe pens/3 ml, paper instructions.