RinFast^® (Solution) Instructions for Use

ATC Code

A10AD05 (Insulin aspart)

Active Substance

Insulin aspart (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Short-acting human insulin analogue

Pharmacotherapeutic Groups

• Hypoglycemic agent – long-acting insulin analogue
• Hypoglycemic agent – short-acting insulin analogue
• Hypoglycemic agent – intermediate-acting insulin

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 an increase in glucose utilization by tissues after insulin binds to receptors on muscle and fat cells, and a simultaneous decrease in the rate of 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 subcutaneous administration is shorter than that of soluble human insulin.

After subcutaneous administration, the action 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. Because of this, Insulin aspart is absorbed much faster from subcutaneous adipose tissue compared to soluble human insulin.

After subcutaneous 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 subcutaneous administration of a dose of 0.15 U/kg 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, leading to a lower C_max (352±240 pmol/L) and a later T_max (60 (interquartile range: 50-90) min). Intra-individual variability in C_max is significantly lower with insulin aspart compared to soluble human insulin, whereas the variability in T_max for insulin aspart is greater.

Indications

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

ICD codes

Dosage Regimen

Solution

Administered subcutaneously.

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 subcutaneous insulin infusions in insulin pumps or administered intravenously 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 is 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 neuropathy.

Skin and subcutaneous tissue disorders uncommon – lipodystrophy; unknown – skin 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 control 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 that was before pregnancy.

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

Use in Hepatic Impairment

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

Use in Renal Impairment

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

Pediatric Use

Not recommended for use in children under 1 year of age, because clinical studies in children under 1 year of age 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 can 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. In this regard, it is recommended to carry out measures aimed at optimizing metabolic control, including monitoring blood glucose levels.

The high rate of development of the hypoglycemic effect should be taken into account when treating patients with concomitant diseases or taking drugs that slow down the absorption of food. In the presence of concomitant diseases, especially of infectious origin, the need for insulin, as a rule, 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 drug 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 the 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 the development of 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.

When using insulin, antibody formation is possible. In rare cases, if antibodies are formed, 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 (for example, 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 working with 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 is 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 the development of chronic heart failure. This fact should be taken into account when prescribing combined therapy with thiazolidinediones and insulin preparations to patients. When prescribing such combination therapy, medical examinations of patients should be carried out to identify signs and symptoms of chronic heart failure, weight gain and the presence of edema. If the 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.