NOVOMIKS30 FleksPen

Active material: insulin aspart dvuhfaznыy
When ATH: A10AD05
CCF: Human insulin analog intermediate-acting with a rapid onset of action
ICD-10 codes (testimony): E10, E11
At KFU: 15.01.01.03
Manufacturer: NOVO NORDISK A/S (Denmark)

Pharmaceutical form, composition and packaging

Suspension for s / c administration white, Homogeneous (containing no lumps, the sample may appear flakes); while standing stratified, forming a white precipitate and a colorless or nearly colorless supernatant; with gentle stirring to form a homogeneous slurry should.

Excipients: mannitol, phenol, cresol, zinc chloride, sodium chloride, sodium dihydrogen phosphate dihydrate, protamine sulfate, Sodium hydroxide, hydrochloric acid, water d / and.

* 1 ED matches 35 g anhydrous insulin aspart.

3 ml – Glass cartridges (1) – pen multidose disposable for multiple injections (5) – packs cardboard.

Pharmacological action

Human insulin analog intermediate-acting with a rapid onset of action.

NovoMiks^®30 FlexPen^® It is a two-phase slurry, consisting of soluble insulin aspart (30% Short-acting insulin analogue) and insulin aspart protamine crystals (70% analog intermediate-acting insulin).

Insulin aspart is produced using recombinant DNA biotechnology using the strain Saccharomyces cerevisiae.

It interacts with a specific receptor cytoplasmic outer cell membrane to form insulin-receptor complex, stimulating intracellular processes, incl. Several key enzymes (geksokinaza, pyruvate, glikogensintetaza). The hypoglycemic effect is associated with an increase in intracellular transport and increased glucose uptake tissues, stimulation of lipogenesis, glikogenogeneza, reducing the rate of hepatic glucose production.

When applied in patients with diabetes mellitus type 1 and 2 drug NovoMiks^®30 FlexPen^® It has the same effect on the level of glycated hemoglobin, as biphasic human insulin 30. Insulin aspart, and human insulin have the same activity in a molar equivalent.

The insulin aspart proline amino acid substitution at position B28 with Aspartic acid molecules reduces the tendency to form hexamers in the soluble fraction of the drug NovoMiks^®30 FlexPen^®, which is observed in the soluble human insulin. Therefore insulin aspart absorbed from subcutaneous fat faster, than soluble insulin, contained in the two-human insulin. Insulin aspart protamine, like human insulin NPH, longer absorbed.

As compared to soluble human insulin, insulin aspart (fast-acting human insulin analog) It begins to act quickly, therefore, it can be administered immediately before a meal (from 0 to 10 minutes before meals). Kristallicheskaya phase (70%) It consists of insulin aspart protamine (human insulin analog average duration), the effect of which is similar to the human insulin isophane.

After s / c administration NovoMiks^®30 FlexPen^® effect develops in 10-20 m. The maximum effect is observed after 1-4 hours after injection. The duration of action of the drug reaches 24 no.

Three-month clinical study in patients with diabetes mellitus type 1 and 2 found, that NovoMiks^®30 FlexPen^® It has the same effect on the level of glycated hemoglobin, as biphasic human insulin 30. Insulin aspart has a similar activity to human insulin on a molar equivalent.

In a clinical study involving patients with diabetes mellitus type 2 (n=341) Patients were randomized to treatment only drug NovoMiks^®30, drug NovoMiks^®30 FlexPen^® in combination with metformin and preparatom preparatom metformin combinations sulyfonilmochevinoy. The primary efficacy variable HbA_1c after 16 weeks of treatment did not differ in patients, receiving NovoMiks^®30 FlexPen^® in combination with metformin in patients, metformin in combination with a sulfonylurea. In this study, 57% patients had a basic level of HbA_1c higher 9%; in these patients, therapy with NovoMiks^®30 in combination with metformin, has led to a significant decrease in HbA_1c, than patients, metformin in combination with a sulfonylurea.

Pharmacokinetics

Absorption

The insulin aspart proline amino acid substitution at position B28 with Aspartic acid molecules reduces the tendency to form hexamers in the soluble fraction NovoMiks^®30 FlexPen^®, which is observed in the soluble human insulin. Therefore insulin aspart (30%) absorbed from the subcutaneous fat faster, than soluble insulin, contained in the two human insuline. Insulin aspart protamine (70%), as human insulin isophane, longer absorbed.

When using NovoMiks^®30 FlexPen^® C_max Serum insulin on average 50% higher, than with biphasic human insulin 30; at the same time to reach C_max on average 2 half. When s / c administration of the drug to healthy volunteers in a dose rate 0.2 U / kg body weight of an average C_max It was 140 ± 32 pmol / L and is reached through 60 m.

In patients with diabetes mellitus type 2 C_max achieved through 95 min and maintained at significantly higher 0 no less 14 h after s / to the introduction.

The dependence of absorption NovoMiks^®30 FlexPen^® from the site of administration has not been studied.

Serum insulin concentration is returned to the original level through 15-18 h after s / c injection.

Deduction

Average T_1/2, reflecting the absorption rate of the protamine bound fraction,, is 8-9 no.

Pharmacokinetics in special clinical situations

Patients older, Children and patients with impaired hepatic or renal function study of the pharmacokinetics of the drug NovoMiks^®30 FlexPen^® not performed.

Testimony

- Diabetes.

Dosage regimen

The drug is designed to s / c administration. The drug NovoMiks^®30 FlexPen^® you can not enter in /.

Dose set individually based on indicators of blood glucose levels. The average daily dose ranges from 0.5 to 1 U / kg body weight. When insulin resistance (eg, obese patients) daily insulin requirement may be increased, and in patients with residual endogenous insulin secretion – downgraded.

Patients with diabetes mellitus type 2 NovoMiks^®30 FlexPen^® It can be administered as a monotherapy, in combination with metformin in cases, When blood glucose insufficiently regulated one with metformin. The recommended starting dose NovoMiks^®30 FlexPen^® in combination with metformin is 0.2 U / kg / day. The dose should be adjusted according to the individual need for insulin, based on the content of glucose in the blood.

NovoMiks^®30 FlexPen^® should be administered immediately before a meal; if necessary – after meals. The temperature of the injected drug must comply room.

Injections produce n / k to the thigh or the anterior abdominal wall, as well as the shoulder or buttocks. It is necessary to change the injection site within the anatomical region, to prevent the development of lipodystrophy. The insulin will work more quickly when it is administered to the anterior abdominal wall.

As with any other insulin, the duration of action of the drug NovoMiks^®30 FlexPen^® dose dependent, insertion site, the intensity of the blood flow, temperature and level of physical activity. The dependence of absorption NovoMiks^®30 FlexPen^® from the site of administration has not been studied.

How to use the drug NovoMiks^®30 FlexPen^®

Before applying NovoMiks^®30 FlexPen^® you should check the label, to ensure the desired type of insulin using.

The patient should be informed about the importance of mixing the slurry NovoMiks^®30 immediately before use. The stirred suspension should be uniformly white and turbid.

NovoMiks^®30 FlexPen^® It is intended only for personal use, syringe pen FleksPen^® can not be refilled. Pen FleksPen^® used with short needles NovoFayn labeled S.

NovoMiks^®30 FlexPen^® You can not use, if the device FleksPen^® It damaged or broken, and after an accidental fall device, when there is a risk of leakage of insulin; if the drug is stored in unacceptable conditions, or been frozen; If the specimen had white lumps or if white particles adhere to the bottom or to the wall of the cartridge, giving him the appearance of a frozen.

Side effect

Adverse Reactions, related to the effect on carbohydrate metabolism: often – gipoglikemiâ, the symptoms of which may include pale skin, cold sweat, nervousness, tremor, anxiety, unusual tiredness or weakness, disorientation, impaired concentration, dizziness, pronounced hunger, temporary blurred vision, Headache, nausea, taxikardiju. Severe hypoglycemia may lead to unconsciousness, temporary or permanent impairment of brain function and death.

Hypoglycemia occurs when the, If too high a dose of insulin with respect to the body's need for insulin. In clinical studies, as well as postmarketing observations, the frequency of this complication is varied depending on the population studied, dosing regimens, therefore specify the frequency of hypoglycemia in patients receiving NovoMiks^®30 FlexPen^® It does not seem possible. In clinical studies, there was no difference in the incidence of hypoglycemia when taking insulin aspart and human insulin preparations.

The incidence of other side effects: sometimes (> 1/1000, < 1/100); rarely (>1/10 000, < 1/1000); rarely (< 1/10 000), including individual cases.

From the central and peripheral nervous system: rarely – perifericheskaya neuropathy. The rapid improvement in glycemic control may be associated with development of acute neuropathic pain, which is generally reversible.

On the part of the organ of vision: rarely – refractive error (possible at the beginning of therapy, usually reversible), diabeticheskaya retinopathy. Long adequate glycemic control decreases the risk of progression of diabetic retinopathy. However, the increase in the intensity of insulin therapy with abrupt improvement in glycemic control may be associated with transient worsening of diabetic retinopathy.

Allergic reactions: rarely – hives, rash; rarely – anaphylactic reactions (life-threatening), which may include generalized rash, itch, increased perspiration, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia and blood pressure reduction. Local allergic reactions (redness, edema, itch) They are usually transient and disappear with continued treatment.

Local reactions: rarely – lipodystrophy at the site of injection, in case of impossibility to change within the anatomical region, hypersensitivity reactions (redness, edema, itch; usually transient, disappear with continued treatment).

Other: rarely – swelling (possible at the beginning of therapy, usually transient).

Contraindications

- Gipoglikemiâ;

- Increased individual sensitivity to insulin aspart or other ingredients.

It is not recommended to use the drug in children and adolescents under the age of 18 years, tk. clinical studies on the use of NovoMiks^®30 FlexPen^® in patients in this age group have not been conducted.

Pregnancy and lactation

Clinical experience with insulin aspart in pregnancy is limited.

Between the possible occurrence and for the duration of pregnancy is necessary to conduct a thorough monitoring of patients with diabetes and control the level of glucose in the blood plasma. The need for insulin, usually, decreases in I trimester, and gradually increased in the II and III trimester of pregnancy. Shortly after birth, insulin requirements quickly return to the level, that was before pregnancy.

During the period of breastfeeding preparation can be used without restrictions. Insulin nursing mother presents no risk to the baby. However, it may be necessary to dose adjustment NovoMiks^®30 FlexPen.

IN experimental studies animals not found differences between the embryotoxic and teratogenic action of insulin aspart and human insulin.

Cautions

Inadequate dosage or discontinuation of treatment, particularly diabetes Type 1 (insulinzavisimom) may lead to hyperglycemia or diabetic ketoacidosis – states, where there is a risk of death.

After compensation of carbohydrate metabolism, eg, when intensified insulin therapy, patients can change their typical symptoms of hypoglycemia-precursors, what patients should be informed.

NovoMiks^®30 FlexPen^® It should be used in direct connection with a meal. Note speed of onset of effect of the drug in the treatment of patients, with concomitant diseases or taking drugs, slowing down the absorption of food. In the presence of comorbidities, especially infectious nature, insulin requirements, usually, increases. Violation of renal or hepatic function may lead to a decrease in insulin requirements.

Skipping meals or unplanned exercise can lead to hypoglycaemia. Compared with biphasic human insulin administration NovoMiks^®30 FlexPen^® It has a stronger hypoglycemic effect in the first 6 hours after injection. Concerning, in some cases, may require dose adjustment of insulin and / or the nature of power.

Transfer the patient to a new type of insulin or insulin product of another manufacturer must be carried out under strict medical supervision. If you change the concentration, type, manufacturer and type (human insulin, Insulin of animal origin, human insulin analog) insulin and / or method of manufacture may require a change in dose. Patients, perehodyashtim treatment NovoMix^®30 FlexPen^®, You may need to change the dose in comparison with the previously used doses of insulin. If necessary, dose adjustment, it can be made already at the first administration of the preparation or during the first weeks or months of treatment. Besides, change in dose may be necessary when changing the diet and increased physical activity. Physical exercise, performed immediately after a meal, increase the risk of hypoglycaemia.

As with other insulin formulations, apply NovoMiks^®30 FlexPen^® in combination with pioglitazone with caution, assessing the risk of adverse events in patients, related to fluid retention. There are also reports of heart failure in the application of pioglitazone in combination with insulin, especially in patients with risk factors for heart failure. In applying the drug NovoMiks^®30 FlexPen^® in combination with pioglitazone patients should be evaluated for signs and symptoms of heart failure, weight gain and edema appearance. By increasing the insulin sensitivity in patients during treatment with pioglitazone in combination with insulin increases the risk of dose-related hypoglycaemia, and may require dose reduction of insulin.

Do not use NovoMiks^®30 FlexPen^® in insulin pumps.

Effects on ability to drive vehicles and management mechanisms

The ability to focus and speed of reaction can be violated during hypoglycemia and hyperglycemia, which should be considered when administering the drug to patients, engaged in potentially hazardous activities. Patients should be advised to take measures to prevent hypoglycemia and hyperglycemia when driving and operating machinery. This is especially important for patients with absence or reduction in symptoms, precursors of developing hypoglycemia or frequent episodes of hypoglycemia sufferers. In these cases, you should consider the appropriateness of the job, related to the necessity of high concentration and speed of psychomotor reactions.

Overdose

Symptoms: may develop hypoglycemia.

Treatment: mild hypoglycaemia the patient may self-arrest glucose ingestion, sugar or carbohydrate-rich foods. Therefore, patients with diabetes should always carry sugar, confection, biscuits or sugary fruit juice. In severe cases,, loss of consciousness, I / O is introduced 40% Dextrose; / m or s / c – glucagon (0.5-1 mg). After regaining consciousness of the patient is recommended to take food, rich in carbohydrates, to prevent recurrence of hypoglycemia.

Drug Interactions

The hypoglycemic effect of the drug increase oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, Octreotide, sulfonamides, anabolic steroid, tetracikliny, clofibrate, ketoconazole, meʙendazol, pyridoxine, theophylline, cyclophosphamide, fenfluramin, lithium preparations, etanolsoderzhaschie drugs.

The hypoglycemic effect of the drug reduces oral contraceptives, GCS, thyroid hormone drugs, thiazide diuretics, Heparin, tricyclic antidepressants, sympathomimetic, danazol, klonidin, Calcium channel blockers, diazoksid, morphine, phenytoin, nicotine.

Under the influence of reserpine and possibly as a weakening of salicylates, and strengthening of the drug NovoMiks^®30 FlexPen^®.

Beta-blockers may mask the symptoms of hypoglycemia.

Ethanol can enhance and prolong the hypoglycaemic effect of insulin.

Pharmaceutical interaction

Drugs, containing thiols or sulfites, when added to insulin aspart cause its destruction.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a refrigerator at 2 ° to 8 ° C (away from the freezing chamber); Do not freeze, protect from light. Shelf life – 2 year.

After the first use NovoMiks^®30 FlexPen^® It should be kept at a temperature no higher than 30 ° C for 4 weeks. Not used to store the pen in a refrigerator or at temperatures above 30 ° C (If your syringe pen still stored in a refrigerator, before its further use should be made mixing the contents of the pen).

To protect from light NovoMiks^®30 FlexPen^® be sure to close the cap.

The drug should be stored out of reach of children.