NovoMix 30 FlexPen - instructions for use, dose, side effects, contraindications

Active substanceInsulin aspart biphasicInsulin aspart biphasic

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NovoMix® 30 Penfill®

suspension PC

Novo Nordisk A / S Denmark

NovoMix® 30 FlexPen®

suspension PC

Novo Nordisk A / S Denmark

NovoMix® 50 FlexPen®

suspension PC

Novo Nordisk A / S Denmark

NovoMix® 70 FlexPen®

suspension PC

Novo Nordisk A / S Denmark

Dosage form: & nbspsubcutaneous suspension

Composition:

In 1 ml of the drug contains:

active substance: insulin aspart (soluble insulin aspart (30%) and insulin crystals of aspart protamine (70%)) 100 units (3.5 mg);

Excipients: glycerol 16.0 mg, phenol 1.50 mg, metacresol 1.72 mg, zinc 19.6 μg (in the form of zinc chloride), sodium chloride 0,877 mg, sodium hydrogen phosphate dihydrate 1.25 mg, protamine sulfate about 0.32 mg , sodium hydroxide about 2.2 mg, hydrochloric acid about 1.7 mg, water for injection up to 1.0 ml.

1 pre-filled syringe pen (3 ml) contains 300 units.

Description:

Homogenous suspension of white color, not containing lumps. Flakes may appear in the sample. When standing, the suspension stratifies to form a white precipitate and a colorless or almost colorless supernatant. While stirring the contents of the pen-syringe according to the procedure described in the Instruction for medical use, a homogeneous suspension should be formed.

Pharmacotherapeutic group:hypoglycemic agent - a combination of insulin analogues of short and medium duration of action

ATX: & nbsp

A.10.A.D.05 Insulin aspart

Pharmacodynamics:

NovoMix® 30 FlexPen® is a two-phase suspension consisting of a mixture of insulin analogs: soluble insulin aspart (30% short-acting insulin analog) and insulin crystals of aspart protamine (70% insulin analog of average duration of action).

The active substance NovoMix® 30 FlexPen® is an insulin aspart, produced by biotechnology of recombinant DNA using a strain Saccharomyces cerevisiae.

Insulin aspart is an equipotential soluble human insulin based on the molarity index.

Reduction of blood glucose level occurs due to the increase of its intracellular transport after binding of insulin aspart with insulin receptors of muscle and fat tissues and simultaneous inhibition of glucose production by the liver. After a subcutaneous injection of NovoMix® 30, the FlexPan® effect develops within 10-20 minutes. The maximum effect is observed in the range from 1 to 4 hours after the injection.The duration of the drug reaches 24 hours.

In a three-month comparative clinical trial involving patients with type 1 and type 2 diabetes mellitus who received NoviMix® 30 FlexPen® and biphasic human insulin 30 twice daily before breakfast and dinner, it was shown that NovoMix® 30 FlexPen® was more effective in reducing postprandial levels blood glucose (after breakfast and dinner).

A meta-analysis of data from nine clinical trials involving patients with type 1 and type 2 diabetes showed that NovoMix® 30 FlexPen®, when administered before breakfast and dinner, provides better control of postprandial blood glucose (mean increase in prandial glucose levels after breakfast, lunch and dinner), compared to human biphasic insulin 30. Although the fasting glucose concentration in patients using NovoMix® 30 FlexPen® was higher, Novomix® 30 FlexPan® generally had the same effect effect on the concentration of glycosylated hemoglobin (HbA₁_c), as well as biphasic human insulin 30.

In a clinical study involving 341 patients with type 2 diabetes mellitus,patients were randomized to treatment groups only NovoMix® 30 FlexPen®, NovoMix® 30 FlexPen® in combination with metformin and metformin in combination with the sulfonyl urea derivative.

Concentration HbA₁_c after 16 weeks of treatment did not differ in patients who received NovoMix® 30 FlexPen® in combination with metformin and in patients who received metformin in combination with a sulfonylurea compound. In this study, in 57% of patients the baseline concentration HbA₁_c was above 9%; In these patients, therapy with NovoMix® 30 FlexPen® in combination with metformin resulted in a more significant decrease in concentration HbA₁_c, than in patients who received metformin in combination with a sulfonylurea compound.

In another study, patients with type 2 diabetes mellitus with unsatisfactory control glycemia, who took oral hypoglycemic drugs, were randomized into the following groups: those receiving NovoMix® 30 FlexPen® twice a day (117 patients) and receiving insulin glargine once a day (116 patients). After 28 weeks of use, the average decrease in concentration HbA₁_c in the NovoMix® 30 FlexPen® group was 2.8% (the initial mean was 9.7%). In 66% and 42% of patients using NovoMix® 30 FlexPen®, at the end of the study the values HbA1_c were below 7% and 6.5% respectively. The mean fasting plasma glucose decreased by about 7 mmol / l (from 14.0 mmol / L at the beginning of the study to 7.1 mmol / L).

The results of a meta-analysis of data from clinical trials involving patients with type 2 diabetes showed a reduction in the total number of episodes of nocturnal hypoglycemia and severe hypoglycemia with NovoMix® 30 FlexPen®, as compared to the two-phase human insulin 30. The overall risk day hypoglycaemia in patients treated with NovoMix® 30 FlexPen® was higher.

Children and adolescents:

A 16-week clinical trial was conducted comparing blood glucose levels after meals with NovoMix® 30 FlexPen® (before meals), human insulin / biphasic human insulin 30 (before meals), and isofan-insulin (administered at bedtime) . The study involved 167 patients aged 10 to 18 years. Mean values HbA₁_c in both groups remained close to the initial values throughout the study.Also, when NovoMix® 30 FlexPen® or biphasic human insulin 30 was used, there was no difference in the incidence of hypoglycemia.

A double-blind, cross-sectional study was conducted in the population of patients aged 6 to 12 years (54 patients in total, 12 weeks for each type of treatment). The incidence of hypoglycemia and increased post-prandial glucose in the group of patients using NovoMix® 30 FlexPen® were significantly lower than those in the group of patients using biphasic human insulin 30. Values HbA₁_cAt the end of the study, the use of biphasic human insulin 30 was significantly lower than in the group of patients using NovoMix® 30 FlexPen®.

Elderly patients:

Pharmacodynamics NovoMix® 30 FlexPen® in patients of elderly and senile age has not been studied. However, in a randomized, double-blind, cross-over study, 19 patients with type 2 diabetes aged 65-83 years (mean age 70 years) compared the pharmacodynamics and pharmacokinetics of insulin aspart and soluble human insulin.Relative differences in the values of pharmacodynamics (the maximum rate of glucose infusion - GIR_max and the area under the curve of its infusion rate within 120 minutes after the administration of insulin preparations - AUC_Gir_,_0-120_min) between insulin aspart and human insulin in elderly patients were similar to those in healthy volunteers and in younger patients with diabetes mellitus.

Pharmacokinetics:

In insulin aspart, the replacement of the amino acid proline in position B28 with aspartic acid reduces the tendency of the molecules to form hexamers in the soluble fraction NovoMix® 30 FlexPen®, which is observed in soluble human insulin. Concerning insulin aspart (30%) is absorbed from the subcutaneous fat faster than soluble insulin, contained in a two-phase human insulin. The remaining 70% is attributable to the crystalline form of protamine-insulin aspart, the rate of absorption of which is the same as that of human NPH insulin.

The maximum serum insulin concentration after administration of NovoMix® 30 FlexPene® is 50% higher than that of biphasic human insulin 30, and the time to achieve it is half as long as compared with biphasic human insulin 30.

In healthy volunteers, after subcutaneous administration of NovoMix® 30 at the rate of 0.20 U / kg body weight, the maximum serum insulin concentration in blood serum was reached after 60 minutes and was 140 ± 32 pmol / L. Duration of half life (t_1/2) of NovoMix® 30 FlexPen®, which reflects the rate of absorption of the protamine-related fraction, was 8-9 hours. The insulin level in the serum returned to the baseline 15-18 hours after subcutaneous administration of the drug. In patients with type 2 diabetes, the maximum concentration was reached 95 minutes after administration and remained above the original at least 14 hours.

Patients of elderly and senile age:

The study of the pharmacokinetics of NovoMix® 30 in elderly and senile patients was not carried out. However, the relative differences in pharmacokinetics between insulin aspart and human soluble insulin in elderly patients with type 2 diabetes (age 65-83 years, mean age 70 years) were similar to those in healthy volunteers and in younger patients with diabetes mellitus. In elderly patients there was a decrease in the rate of absorption, which led to a slowdown t_max (82 minutes (interquartile range: 60-120 minutes)), while the average maximum concentration of C_m_Oh was similar to that observed in younger patients with type 2 diabetes, and slightly less than in patients with type 1 diabetes.

Patients with impaired renal and hepatic function:

The pharmacokinetics of NovoMix® 30 FlexPen® in patients with impaired renal and hepatic function was not studied. Nevertheless, with an increase in the dose of the drug in patients with varying degrees of renal and hepatic impairment, there was no change in the pharmacokinetics of soluble insulin aspart.

Children and teens:

The pharmacokinetic properties of NovoMix® 30 FlexPen® in children and adolescents have not been studied. However, the pharmacokinetic and pharmacodynamic properties of soluble insulin aspart have been studied in children (6-12 years old) and in adolescents (13-17 years old) with type 1 diabetes mellitus.

In patients of both age groups insulin aspart characterized by rapid absorption and values t_max, similar to those of adults. However, the values of C_m_Oh in two age groups were different, which indicates the importance of individual selection of insulin aspart doses.

Preclinical safety data

Pre-clinical studies have not identified any hazard to humans, based on data from generally accepted pharmacological safety studies, re-use toxicity, genotoxicity, and reproductive toxicity.

In the tests in vitro, including binding to insulin and IGF-1 receptors and effects on cell growth, it was shown that the properties of insulin aspart are similar to those of human insulin. The results of the studies also showed that the dissociation of the binding of insulin aspart with insulin receptors is equivalent to that of human insulin.

Indications:Diabetes.

Contraindications:

Increased individual sensitivity to insulin aspart or any of the components of the drug.

It is not recommended for use in children under 6 years of age. clinical trials of NovoMix® 30 Penfill® have not been performed.

Pregnancy and lactation:

Clinical experience of the drug NovoMix® 30 FlexPen® when pregnancy is limited.

Research on the use of the drug NovoMix® 30 FlexPen® in pregnant women were not conducted.Nevertheless, data from two randomized controlled clinical trials (157 and 14 pregnant women, respectively insulin aspart in the basal bolus regimen), no adverse effects of insulin aspart during pregnancy or fetus / newborn health were compared with soluble human insulin. In addition, in a clinical randomized study involving 27 women with gestational diabetes who received insulin aspart and soluble human insulin (insulin aspart received 14 women, human insulin - 13), similar safety profiles were demonstrated for both types of insulin.

In the period of possible pregnancy and throughout its term, it is necessary to carefully monitor the status of patients with diabetes mellitus, and monitor the concentration of glucose in the blood. The need for insulin, as a rule, decreases in the first trimester and gradually rises in the II and III trimesters of pregnancy. Shortly after birth, the need for insulin quickly returns to the level that was before pregnancy.

During lactation NovoMix® 30 FlexPen® can be used without restrictions. The introduction 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 NovoMix® 30 FlexPen®.

Dosing and Administration:

NovoMix® 30 FlexPen® is intended for subcutaneous administration. Do not administer NovoMix® 30 FlexPen® intravenously, as this can lead to severe hypoglycemia. You should also avoid intramuscular injection of NovoMix® 30 FlexPen®. Do not use NovoMix® 30 FlexPen® for subcutaneous insulin infusions (PPII) in insulin pumps.

The dose of NovoMix® 30 FlexPen® is determined by the doctor individually in each case, in accordance with the patient's needs. To achieve the optimal level of glycemia, it is recommended to monitor the concentration of glucose in the blood and correct the dose of the drug.

Patients with type 2 diabetes NovoMix® 30 FlexPen® can be prescribed both in monotherapy and in combination with oral hypoglycemic drugs in those cases where the blood glucose level is not adequately regulated by oral hypoglycemic drugs alone.

Initiation of therapy

For patients with type 2 diabetes mellitus, who are prescribed insulin for the first time, the recommended initial dose of NovoMix® 30 FlexPen® is 6 units before breakfast and 6 units before dinner. It is also possible to administer 12 units of NovoMix® 30 FlexPen® once a day in the evening (before dinner).

Transfer of the patient from other insulin preparations

When transferring a patient from biphasic human insulin to NovoMix® 30, FlexPen® should be started with the same dose and administration regimen. Then adjust the dose according to the individual needs of the patient (see the recommendations for titrating the dose of the drug below). As always, during the transfer of a patient to a new type of insulin, strict medical control is necessary during the transfer of the patient and in the first weeks of using the new drug.

Intensification of therapy

To strengthen NovoMix® 30 FlexPen® therapy is possible by switching from a single daily dose to a double dose. It is recommended after passing the dose of 30 units of the drug to switch to NovoMix® 30 FlexPen® twice a day, dividing the dose into two equal parts - morning and evening (before breakfast and dinner).

Switch to NovoMix® 30 FlexPen® threeonce a day is possible by dividing the morning dose into two equal parts and introducing these two parts in the morning and at lunch (three times the daily dose).

Correction of dose

To adjust the dose of NovoMix® 30 FlexPen®, the lowest fasting blood glucose concentration obtained during the last three days is used.

To assess the adequacy of the previous dose, use the blood glucose value before the next meal.

Dose adjustment can be performed once a week until the target value is reached HbA₁_c.

Do not increase the dose of the drug, if this period was observed hypoglycemia.

Dose adjustment may be necessary if the patient's physical activity is increased, his usual diet changes, or if there is a concomitant disease.

To correct the dose of NovoMix® 30 FlexPen®, the following recommendations for dose titration are recommended:

Concentration of blood glucose in front of food		Adjustment doses NovoMix® 30
<4.4 mmol / l	<80 mg / dL	-2ED
4.4-6.1 mmol / l	80-110 mg / dL	0 (not required)
6.2-7.8 mmol / l	111-140 mg / dL	+ 2ED
7.9-10 mmol / L	141-180 mg / dL	+ 4ED
> 10 mmol / l	> 180 mg / dL	+ 6ED

Special patient groups

As always when using insulin preparations, patients of special groups should more closely monitor the concentration of glucose in the blood and adjust the dose of insulin aspart individually.

Patients of elderly and senile age:

NovoMix® 30 FlexPen® can be used in elderly patients, but experience with oral hypoglycemic agents in patients older than 75 years is limited.

Patients with kidney and liver failure:

In patients with renal or hepatic insufficiency, the need for insulin can be reduced.

Children and adolescents:

NovoMix® 30 FlexPen® can be used to treat children and adolescents over the age of 10 years when pre-mixed insulin is preferred. There are limited clinical data for children aged 6-9 years (see section "Pharmacodynamic properties").

NovoMix® 30 FlexPene® should be injected subcutaneously into the thigh or anterior abdominal wall. If desired, the drug can be injected into the shoulder or buttock area.

It is necessary to change the injection site within the anatomical area to prevent the development of lipodystrophy.

As with any other insulin preparation, the duration of NovoMix® 30 FlexPen® depends on the dose, site of administration, blood flow intensity, temperature and physical activity level.

Compared with the two-phase human insulin NovoMix® 30, FlexPen® starts to act more quickly, so it should be administered immediately before meals. If necessary, NovoMix® 30 FlexPene® can be administered shortly after eating.

Side effects:

Adverse reactions observed in patients using NovoMix® 30 are mainly due to the pharmacological effect of insulin. The most common undesirable phenomenon in the use of insulin is hypoglycemia. The incidence of side effects on the background of NovoMix® 30 varies depending on the patient population, the dosage regimen and the control of glycemia.

At the initial stage of insulin therapy, refractive disorders, edema and reactions may occur at the site of injection (including pain, redness, hives, inflammation, hematoma, swelling and itching at the injection site).These symptoms are usually temporary. Rapid improvement in glycemic control can lead to a state of "acute pain neuropathy," which is usually reversible.

Intensification of insulin therapy with a sharp improvement in carbohydrate metabolism control may lead to a temporary deterioration in the state of diabetic retinopathy, while a prolonged improvement in glycemic control reduces the risk of progression of diabetic retinopathy.

The list of side effects is presented in the table.

All of the side effects presented below, based on data from clinical trials, are grouped according to the frequency of development according to MedDRA and organ systems. The incidence of side effects is defined as: very often (≥ 1/10); often (≥ 1/100 to <1/10); infrequently (≥1 / 1,000 to <1/100); rarely (≥1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000) and unknown (impossible to estimate based on available data).

Immune system disorders	Infrequent - hives, skin rashes, skin rashes
Immune system disorders	Very rarely - anaphylactic reactions *
Disorders from the metabolism and nutrition	Very often - hypoglycemia *
Disturbances from the nervous system	Rarely - peripheral neuropathy ("acute pain neuropathy")
Disturbances on the part of the organ of sight	Infrequent refractive disorders
Disturbances on the part of the organ of sight	Infrequently - diabetic retinopathy
Disturbances from the skin and subcutaneous tissues	Infrequent - lipodystrophy *
General disorders and disorders at the site of administration	Infrequently - reactions in places of administration
	Infrequent - swelling

*Cm. "Description of individual adverse reactions"

Description of individual adverse reactions:

Anaphylactic reactions

Very rare reactions of generalized hypersensitivity (including generalized skin rash, itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, rapid heart rate, lowering of blood pressure), which are potentially life-threatening, have been noted.

Hypoglycaemia

Hypoglycemia is the most common side effect. It can develop if the dose of insulin is too high in relation to the need for insulin. Severe hypoglycemia can lead to loss of consciousness and / or convulsions, temporary or irreversible impairment of brain function up to a lethal outcome.Symptoms of hypoglycemia, as a rule, develop suddenly. They may include cold sweats, pale skin, increased fatigue, nervousness or tremor, anxiety, unusual fatigue or weakness, disorientation, decreased concentration, drowsiness, severe hunger, visual impairment, headache, nausea and heart palpitations .

Clinical studies have shown that the incidence of hypoglycemia varies depending on the patient population, dosing regimen, and glycemic control. Clinical studies showed no difference in the overall incidence of episodes of hypoglycemia between patients receiving insulin aspart therapy and patients using human insulin preparations.

Lipodystrophy

There were reports of infrequent cases of development of lipodystrophy. Lipodystrophy can develop at the site of injection.

Overdose:

A certain dose required for an insulin overdose has not been established, but hypoglycemia can develop gradually if too high doses of insulin are administered relative to the patient's need.

- Light hypoglycemia the patient can eliminate himself by taking glucose or sugar-containing foods. Therefore, patients with diabetes are encouraged to constantly carry with them sugar-containing foods.

- In case of severe hypoglycemia, when the patient is unconscious, should be administered from 0.5 mg to 1 mg glucagon intramuscularly or subcutaneously (can be administered by a trained person) or intravenously glucose solution (dextrose) (may be administered only by a medical professional). It is also necessary to introduce intravenous dextrose in the case if the patient does not regain consciousness 10-15 minutes after the introduction of glucagon. After restoration of consciousness, the patient is recommended to take a carbohydrate-rich food to prevent the recurrence of hypoglycemia.

Interaction:

There are a number of drugs that affect the need for insulin.

Hypoglycemic action of insulin increases oral hypoglycemic drugs, monoamine oxidase inhibitors, angiotensin converting enzyme inhibitors, carbonic anhydrase inhibitors, nonselective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, salicylates.

Hypoglycemic action of insulin weakens oral contraceptives, glucocorticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, somatropin, danazol, clonidine, blockers of "slow" calcium channels, diazoxide, morphine, phenytoin, nicotine.

Beta-blockers can mask symptoms of hypoglycemia.

Octreotide / lanreotide can both increase and decrease the body's need for insulin.

Alcohol can increase or decrease the hypoglycemic effect of insulin.

Incompatibility

Since compatibility studies have not been carried out, NovoMix® 30 FlexPen® should not be mixed with other drugs.

Special instructions:

Before a long trip associated with the change of time zones, the patient should consult with his attending physician, as changing the time zone means that the patient must take food and inject insulin at another time.

Hyperglycaemia

Insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes, can lead to the development of hyperglycemia or diabetic ketoacidosis.Typically, the first symptoms of hyperglycemia appear gradually over several hours or days. Symptoms of hyperglycemia are thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone in the exhaled air. Without proper treatment, hyperglycemia in patients with type I diabetes can lead to diabetic ketoacidosis - a condition that is potentially lethal.

Hypogluandchemium

Skipping meals or unplanned intense exercise can lead to hypoglycemia. Hypoglycemia can also develop if the dose of insulin is too high in relation to the patient's need (see the "Side effect" and "Overdose" sections).

Compared with a two-phase human insulin NovoMix® 30 FlexPen® has a more pronounced hypoglycemic effect within 6 hours after administration. In this regard, in some cases, you may need to adjust the dose of insulin and / or the nature of nutrition.

After compensation of carbohydrate metabolism, for example, with intensified insulin therapy,patients may change typical for their symptoms-precursors of hypoglycemia, which patients should be informed about. Common symptoms-precursors can disappear with prolonged course of diabetes.

Stricter control of glycemia in patients may increase the risk of developing hypoglycemia, so increasing the dose of NovoMix® 30 FlexPen® must be carried out under strict medical supervision, as indicated in the section "Method of administration and dose ".

Since NovoMix® 30 FlexPen® should be used in direct connection with food intake, it should be taken into account the high rate of onset of the drug effect in the treatment of patients who have concomitant diseases or who take medications that slow food intake. Concomitant diseases, especially infectious and accompanied by fever, usually increase the body's need for insulin. Correction of the dose of the drug may also be required if the patient has concomitant diseases of the kidneys, liver, adrenal, pituitary or thyroid gland disorders.

When transferring the patient to other types of insulin, early symptoms-precursors of hypoglycemia may change or become less pronounced compared to those observed with the application of the previous type of insulin.

Transfer of a patient from other insulin preparations

Transfer of the patient to a new type of insulin or an insulin preparation of another manufacturer must be carried out under strict medical supervision. If the concentration, type, producer and species (human insulin, human insulin analog) of insulin preparations and / or production method changes, a dose change may be required. Patients switching from other insulin preparations to NovoMix® 30 FlexPen®, it may be necessary to increase the frequency of injections or dose changes 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 injection of the drug or during the first weeks or months of treatment.

Reactions at the site of administration

As with other insulin preparations, reactions at the injection site may develop, which is manifested by pain, redness, hives, inflammation, bruising, swelling and itching.Regular change of injection site in the same anatomical area reduces the risk of these reactions. Reactions usually disappear for a few days to several weeks. In rare cases, it may be necessary to cancel NovoMix® 30 FlexPen® due to reactions at the site of administration.

The simultaneous use of drugs of the thiazolidinedione group and insulin preparations

Cases of chronic heart failure in the treatment of patients with thiazolidinediones in combination with insulin preparations have been reported, especially if such patients have risk factors for developing chronic heart failure. This fact should be taken into account when appointing patients combination therapy with thiazolidinediones and insulin preparations. In the appointment of such combination therapy, it is necessary to conduct medical examinations of patients to identify signs and symptoms of chronic heart failure, increase in body weight and the presence of edema. If the symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

Antibodies to insulin

With the use of insulin, the formation of antibodies is possible.In rare cases, the formation of antibodies may require a dose adjustment of insulin to prevent cases of hyperglycemia or hypoglycemia.

Instructions for patients on the use of NovoMix® 30 FlexPen®

Do not use NovoMix® 30 FlexPen®:

- If you are allergic (hypersensitive) to insulin aspart or any of the components included in the NovoMix® 30 FlexPene® preparation (see "Composition").

- If you feel the approach of hypoglycemia (low blood sugar) (see section "Hypoglycemia ").

- For subcutaneous insulin infusions (PPII) in insulin pumps.

- If FlexPen® was dropped, or it was damaged or crushed.

- If the storage conditions of the drug have been violated or it has been frozen.

- If insulin does not become uniformly white and cloudy after mixing.

- If in the preparation after mixing left white lumps or if white particles stick to the bottom or walls of the cartridge.

Before using NovoMix® 30 FlexPen®:

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

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

- NovoMix® 30 FlexPan® and needles are for personal use only.

NovoMix® 30 is intended for subcutaneous injections. Never administer this insulin intravenously or intramuscularly.

Each time, change the injection site within the anatomical area. This will help reduce the risk of seals and ulcers at the injection site. The best places for injections are: anterior abdominal wall, buttocks, anterior thigh or shoulder. Insulin will act faster if it is injected into the anterior abdominal wall. Regularly monitor blood glucose.

How to handle NovoMix® 30 FlexPen®

Carefully read the enclosed instruction for patients on the use of NovoMix® 30 FlexPen® and strictly observe it.

Instructions for patients on the use of NovoMix® 30 FlexPen®

Please read this manual carefully before using your NovoMix® 30 FlexPen®

NovoMix® 30 FlexPen® is a unique insulin syringe pen with a dispenser. The injected dose of insulin, ranging from 1 to 60 units, can vary in steps of 1 unit.

NovoMix® 30 FlexPen® is designed for Use with NovoFine® or NovoTvist® disposable needles up to 8 mm in length. As a precaution, always carry a spare insulin delivery system in case you lose or damage your NovoMix® 30 FlexPan®.

Preparing NovoMix® 30 FlexPen®

Check the label to make sure that your FlexPen® contains the type of insulin you need. Before the first injection, you need to mix insulin:

A. To facilitate mixing, allow the product to warm to room temperature. Remove the cap from the syringe pen.

B. Roll the syringe handle between your hands 10 times - it is important that it is in a horizontal position.

C. Lift the syringe handle up and down 10 times, as shown in Figure C, so that the glass ball moves from one end of the cartridge to the other. Repeat the manipulations indicated in points B and C until the contents of the cartridge become evenly white and cloudy.

Before each next injection, mix the contents as shown in Figure C, at least 10 times until the contents of the cartridge become evenly white and cloudy.

After mixing, immediately inject.

- Always ensure that at least 12 units of insulin remain in the cartridge to ensure even mixing. If there are less than 12 units left, use the new NovoMix® 30 FlexPen®.

Attaching the needle

D. Remove the protective sticker from the disposable needle. Carefully and tightly screw the needle onto NovoMix® 30 FlexPan®.

E. Remove the outer cap of the needle, but do not throw it away.

F. Remove and discard the inner needle cap.

- For each injection, use a new needle to prevent infection.

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

- To avoid accidental injections, never put the inner cap back on the needle.

Insulin intake check

Even with the correct use of the syringe pen, a small amount of air can accumulate in the cartridge before each injection. To prevent the ingress of air bubbles and ensure the introduction of the correct dose of the drug:

G. Dial 2 units of the drug by turning the dose selector.

N. While holding the NovoMix® 30 FlexPen® with the needle up, tap the cartridge lightly with your fingertip several times to allow air bubbles to move to the top of the cartridge.

I. While holding the needle with the needle up, press the trigger button all the way. The dosage selector will return to zero. At the end of the needle should appear a drop of insulin. If this does not happen, replace the needle and repeat the procedure, but no more than six times.

If insulin does not come from the needle, this indicates that the pen syringe is faulty and is not subject to further use.

Dose setting

Make sure that the dose selector is set to "O"

J. Dial the number of units needed for the injection.

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

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

- You can not use a residue scale to measure the dose of insulin.

Introduction of insulin

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

TO. To do the injection, press the start button all the way until "O" appears opposite the dosing indicator.Be careful: when you inject the drug, you should only press the start button. When the selector is rotated, the dose will not enter the dose.

L. Hold the start button all the way down until the needle is removed from under the skin. After injection, leave the needle under the skin for at least 6 seconds. This will ensure the introduction of a full dose of insulin.

M. Point the needle into the outer cap of the needle without touching the cap. When the needle enters, insert the outer cap and unscrew the needle. Throw out the needle, observing the precautionary measures, and close the syringe handle with the cap (see Fig. A-M).

- Remove the needle after each injection and never store NovoMix® 30 FlexPen® with attached needle. Otherwise, it is possible to drain liquid from NovoMix® 30 FlexPan®, which may lead to an incorrect dose.

- Persons caring for the patient should take precautions when removing and discarding needles to avoid the risk of accidental needle sticking.

- Throw away the used NovoMix® 30 FlexPen® with the needle disconnected.

- Needles and NovoMix® 30 FlexPan® are for personal use only.

Storage and Care

NovoMix® 30 FlexPen® is designed for efficient and safe use and requires careful handling. In the event of a fall or strong, mechanical impact, it is possible to damage the syringe handle and leakage of insulin.

The surface of NovoMix® 30 FlexPen® can be cleaned with a cotton swab dipped in alcohol. Do not immerse the syringe handle in alcohol, do not wash or lubricate it. this may damage the mechanism.

Do not refill NovoMix® 30 FlexPan®.

Effect on the ability to drive transp. cf. and fur:

The patient's ability to concentrate and the reaction rate can be violated during hypoglycemia that may constitute a danger in situations where these capabilities are especially needed (e.g., when driving or operating machinery).

Patients should be advised to take measures to prevent the development of hypoglycemia in the management of vehicles or work with mechanisms. This is especially important for patients with a lack or decline in symptomatic signs of developing hypoglycemia or suffering from frequent episodes of hypoglycemia.In these cases, the expediency of driving vehicles and performing such work should be considered.

Form release / dosage:Suspension for subcutaneous administration, 100 ED / md.

Packaging:

By 3 ml of the drug in cartridges of glass 1 of hydrolytic class, sealed with stoppers from bromobutyl rubber / polyisoprene on one side and pistons of bromobutyl rubber on the other side. A glass bead is placed in the cartridge, making it easier stirring the slurry.

The cartridge is sealed in a plastic multi-dose disposable syringe pen for multiple injections.

5 multi-dose disposable syringes with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature of 2 to 8 ° C (in the refrigerator), but not next to the freezer. Do not freeze. Used or transported as a spare syringe-pen with the drug is not stored in the refrigerator. Store at a temperature not exceeding 30 ° C. Use within 4 weeks.

To protect from light, store the syringe pen with the cap on.

NovoMix® 30 FlexPen® should be protected from excessive heat and light.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date indicated on the label of the syringe pen and package.

Terms of leave from pharmacies:On prescription

Registration number:P N 015640/01

Date of registration:06.10.2008

The owner of the registration certificate:Novo Nordisk A / SNovo Nordisk A / S Denmark

Manufacturer: & nbsp

NOVO NORDISK, A / S Denmark