Fiasp^® (Solution) Instructions for Use

Marketing Authorization Holder

Novo Nordisk A/S (Denmark)

Manufactured By

Novo Nordisk A/S (Denmark)

Or

Novo Nordisk Producao Farmaceutica do Brasil, Ltda (Brazil)

Labeled By

NOVO NORDISK, A/S (Denmark)

Or

Novo Nordisk Producao Farmaceutica do Brasil, Ltda (Brazil)

Or

NOVO NORDISK, LLC (Russia)

Quality Control Release

NOVO NORDISK, A/S (Denmark)

Or

NOVO NORDISK, LLC (Russia)

ATC Code

A10AB05 (Insulin aspart)

Active Substance

Insulin aspart (Rec.INN registered by WHO)

Dosage Form

Fiasp®

Solution for subcutaneous and intravenous administration 100 U/1 ml: pen-injectors 3 ml 5 pcs.; vial 10 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for s.c. and i.v. administration colorless or almost colorless, transparent, and free of visible particles.

* 1 U of insulin aspart contains 0.035 mg of anhydrous salt-free insulin aspart.
The activity of insulin analogues is expressed in units (U). 1 U of Fiasp^® corresponds to 1 international unit (IU) of human insulin or 1 U of other rapid-acting insulin analogues.

Excipients: phenol, metacresol, glycerol, zinc (as zinc acetate), disodium phosphate dihydrate, arginine hydrochloride, nicotinamide, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.
Solution pH is 7.1.

3 ml (300 U) – glass cartridges, built into disposable multi-dose pen-injectors FlexPen^® (5) – cardboard packs.
3 ml (300 U) – glass cartridges, built into disposable multi-dose pen-injectors FlexTouch^® (5) – cardboard packs.
10 ml (1000 U) – glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Short-acting human insulin analogue

Pharmacotherapeutic Group

Hypoglycemic agent, short-acting human insulin analogue

Pharmacological Action

Insulin aspart is a short-acting human insulin analogue produced by recombinant DNA biotechnology using a strain of Saccharomyces cerevisiae.

The hypoglycemic effect of insulin aspart is due to increased glucose utilization by tissues after insulin binds to receptors on muscle and fat cells, and a simultaneous decrease in glucose production by the liver.

Insulin aspart begins to act faster and simultaneously lowers blood glucose levels more strongly in the first 4 hours after a meal than soluble human insulin. The duration of action of insulin aspart after s.c. administration is shorter than that of soluble human insulin.

After s.c. administration, the effect of insulin aspart begins within 10-20 minutes after administration. The maximum effect is observed 1-3 hours after injection. The duration of action is 3-5 hours.

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 soluble human insulin solution. Therefore, Insulin aspart is absorbed much faster from subcutaneous adipose tissue compared to soluble human insulin.

After s.c. administration of insulin aspart, the time to reach C_max in blood plasma is on average 2 times shorter than after administration of soluble human insulin. C_max averages 492±256 pmol/L and is reached in 40 (interquartile range: 30-40) minutes after s.c. administration of a 0.15 U/kg dose to patients with type 1 diabetes. The insulin concentration returns to baseline 4-6 hours after administration of the drug dose. The absorption rate is somewhat lower in patients with type 2 diabetes, resulting in a lower C_max (352±240 pmol/L) and a later T_max (60 (interquartile range: 50-90) min). Intra-individual variability for C_max is significantly lower with insulin aspart compared to soluble human insulin, whereas the inter-individual variability for C_max for insulin aspart is greater.

Indications

Diabetes mellitus in adults, adolescents, and children over 1 year of age.

ICD codes

Dosage Regimen

Administered s.c.

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

In addition, the drug containing Insulin aspart can be used for prolonged s.c. insulin infusions in insulin pumps or administered i.v. by medical personnel.

To achieve optimal glycemic control, it is recommended to regularly measure blood glucose concentration and adjust the insulin dose.

Usually, the individual daily insulin requirement in adults and children ranges from 0.5 to 1 U/kg of body weight.

Adverse Reactions

Immune system disorders uncommon – urticaria, skin rash, skin eruptions; very rare – anaphylactic reactions.

Metabolism and nutrition disorders very common – hypoglycemia.

Nervous system disorders rare – peripheral neuropathy (acute painful neuropathy).

Eye disorders uncommon – refraction disorders, diabetic retinopathy.

Skin and subcutaneous tissue disorders uncommon – lipodystrophy; not known – cutaneous amyloidosis.

General disorders and administration site conditions uncommon – edema.

Administration site reactions uncommon – injection site reactions.

Contraindications

Hypoglycemia, children under 1 year of age, hypersensitivity to insulin aspart.

Use in Pregnancy and Lactation

Insulin aspart can be used during pregnancy. Careful monitoring of blood glucose concentration and monitoring of pregnant women with diabetes mellitus (type 1 diabetes, type 2 diabetes, or gestational diabetes) is recommended throughout pregnancy and during the period of possible conception. The insulin requirement usually decreases in the first trimester and gradually increases in the second and third trimesters of pregnancy. Soon after delivery, the insulin requirement quickly returns to the level before pregnancy.

Insulin aspart can be used during breastfeeding. However, dose adjustment of this insulin may be necessary.

Use in Hepatic Impairment

In case of liver disease, dose adjustment of insulin may be required.

Use in Renal Impairment

In case of kidney disease, dose adjustment of insulin may be required.

Pediatric Use

Not recommended for use in children under 1 year of age, as clinical studies in children younger than 1 year have not been conducted.

Geriatric Use

In elderly patients, blood glucose levels should be carefully monitored and the dose adjusted individually. There is no experience of use in patients aged 75 years and older.

Special Precautions

Insufficient insulin dose or discontinuation of treatment may lead to the development of hyperglycemia or diabetic ketoacidosis. As a rule, symptoms of hyperglycemia appear gradually, over several hours or days. Symptoms of hyperglycemia are nausea, vomiting, drowsiness, flushed and dry skin, dry mouth, increased urine output, thirst and loss of appetite, as well as the appearance of acetone odor in the exhaled air. Without appropriate treatment, hyperglycemia can lead to death. After compensation of carbohydrate metabolism, for example during intensive insulin therapy, the typical warning symptoms of hypoglycemia for a particular patient may change.

In elderly patients, blood glucose levels should be carefully monitored and the dose adjusted individually. There is no experience of use in patients aged 75 years and older.

In patients with diabetes mellitus, with optimal metabolic control, late complications of diabetes develop later and progress more slowly. Therefore, measures aimed at optimizing metabolic control, including monitoring of blood glucose levels, are recommended.

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 food absorption. In the presence of concomitant diseases, especially of infectious origin, the insulin requirement usually increases.

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

Switching a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under strict medical supervision. When changing the concentration, type, manufacturer, and type (human insulin, animal insulin, human insulin analogue) of insulin preparations and/or manufacturing method, a dose change may be required.

A change in insulin dose may be required when changing diet and during increased physical activity. Exercise performed immediately after a meal may increase the risk of hypoglycemia. Skipping a meal or unplanned physical activity can lead to hypoglycemia.

A significant improvement in the state of 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.

The formation of antibodies is possible when using insulin. In rare cases, with antibody formation, adjustment of the insulin dose may be required to prevent cases of hyperglycemia or hypoglycemia.

Effect on ability to drive vehicles and operate machinery

Patients’ ability to concentrate and reaction speed may be impaired during hypoglycemia and hyperglycemia, which may be dangerous in situations where these abilities are especially necessary (e.g., 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 and operating machinery. This is especially important for patients with absent or reduced severity of warning symptoms of developing hypoglycemia or those suffering from frequent episodes of hypoglycemia. In these cases, the advisability of performing such work should be considered.

Drug Interactions

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, 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, both weakening and enhancement of the action of insulin aspart are possible.

Cases of chronic heart failure have been reported during treatment of patients with thiazolidinediones in combination with insulin preparations, especially in such patients with risk factors for chronic heart failure. This fact should be taken into account when prescribing combined therapy with thiazolidinediones and insulin preparations to patients. When prescribing such combined therapy, medical examinations of patients should be conducted to identify signs and symptoms of chronic heart failure, weight gain, and the presence of edema. If symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

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

Ethanol (alcohol) can both enhance and reduce the hypoglycemic effect of insulin.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.