Epidera® [Insulin glulisin]

Pharmacological properties

insulin glulisin is a recombinant analogue of human insulin, similar in potency. insulin glulisin acts faster and for less time than natural human insulin. the main action of insulin and its analogues, including insulin glulisin, is aimed at regulating glucose metabolism. insulin lowers blood glucose levels by stimulating peripheral glucose utilization, especially in skeletal muscle and adipose tissue, and inhibiting liver glucose synthesis. insulin prevents lipolysis in adipocytes, proteolysis and enhances protein synthesis.

Studies in healthy volunteers and patients with diabetes mellitus have shown that with sc administration of insulin, glulisin acts faster and for a shorter period than regular insulin. If insulin glulisin is used as a s / c injection, a decrease in blood glucose level begins within 10–20 minutes. When s / c administration of insulin glulisin and normal human insulin at a dose of 0.15 U / kg at different times relative to the 15-minute standard meal, it was found that post-prandial glycemic control, similar to that with using regular human insulin, applied 30 minutes before meals. When comparing the hypoglycemic effects of insulin glulisin and normal human insulin 2 minutes before meals, insulin glulisin provided better postprandial control than human short-acting insulin. The use of insulin glulisin 15 minutes after a meal provides glycemic control, similar to that with conventional human insulin, administered 2 minutes before meals.

Obesity. Insulin glulisin preserves the onset of effect in obese patients. Time to reach 20% of the total AUC and AUC_{0–2 h}, which are indicative of the early action of insulin in reducing glucose, were 114 min and 427 mg / kg for insulin glulisin and 121 min and 354 mg / kg for lispro insulin, 150 min and 197 mg / kg for short-acting human insulin, respectively.

Race and gender. In controlled clinical trials in adults, insulin glulisin did not show differences in safety and efficacy in subgroups that differed by race and gender.

Pharmacokinetics Faster absorption of insulin glulisin is provided by replacing the amino acid asparagine at position B3 of human insulin with lysine and lysine at position B29 with glutamic acid.

Absorption and bioavailability. Pharmacokinetic profiles in healthy volunteers and patients with type I or type 2 diabetes mellitus demonstrated that the level of absorption of insulin glulisin was 2 times higher and the maximum concentration was approximately 2 times higher compared to conventional human insulin.

In patients with type I diabetes mellitus after subcutaneous injection at a dose of 0.15 U / kg, the time to reach T_max for insulin, glulisin was 55 min, C_max in blood - 82 ± 1.3 mcED / ml in comparison with T_max 82 min and C_max 46 ± 1.3 mcED / ml for normal human insulin. The average residence time of insulin glulisin in the body was shorter (98 min) than that of ordinary human insulin (161 min).

In patients with type II diabetes mellitus after sc administration of insulin glulisin at a dose of 0.2 PIECES / kg C_max in is 91 mcED / ml with a confidence interval of 78–104 mcED / ml.

With subcutaneous injection of insulin glulisin in the anterior abdominal wall, thigh or deltoid muscle, absorption of the drug is faster when introduced into the abdomen than into the thigh. Absorption at the injection site in the deltoid muscle has an average value between the two aforementioned indicators. The absolute bioavailability (70%) of insulin glulisin is similar when administered at the above injection sites and has a low individual variability (11% CV). The iv bolus use of insulin glulisin was the reason for a large systemic effect compared to those with sc injection, and the value of C_max was about 40 times larger.

Distribution and withdrawal. The distribution and excretion of insulin glulisin and ordinary human insulin after iv administration is similar, with a distribution volume of 13 and 22 liters, and T_½ - 13 and 18 minutes respectively.

After s / c use, insulin glulisin is excreted faster than normal human insulin, with an average duration of T_½ 42 min for insulin glulisin and 86 min for regular insulin. When analyzing a cross-sectional study of insulin glulisin involving healthy volunteers or patients with type I or type 2 diabetes mellitus, the average duration of T_½ was 37–75 min (confidence interval).

Insulin glulisin, like human insulin, binds poorly to plasma proteins.

Features of the use of the drug in certain groups of patients

Patients with impaired renal function. With impaired renal function, the need for insulin may decrease, but the ability of insulin glulisin to act quickly remains.

Patients with impaired liver function. The pharmacokinetic properties of insulin glulisin have not been studied in patients with impaired liver function.

Elderly patients. For elderly patients with diabetes mellitus, there is a very limited database of pharmacokinetics of the drug.

Children and teens. The pharmacokinetic and pharmacodynamic properties of insulin glulisin in children (7–11 years old) and adolescents (12–16 years old) with type I diabetes mellitus are as follows: insulin glulisin is rapidly absorbed in patients of both age groups and has the same T_max and C_maxas in adults. The administration of glulisin insulin immediately before meals for children and adolescents provides better postprandial glycemic control compared to conventional human insulin, as in adult patients. The glucose deviation (AUC) is 641 mg / h / dl for insulin glulisin and 801 mg / h / dl for normal human insulin.

Preclinical data on the safety of use do not indicate the presence of toxicity (except associated with hypoglycemia), which was different from normal human insulin or was clinically significant for humans.

Indications

Diabetes mellitus, when there is a need for the use of insulin in adults, adolescents and children aged 6 years and older.

Application

The strength of the drug is expressed in units used exclusively for epider® and differing from ME or units expressing the strength of the action of other insulin analogs.

The drug Epidera^® can be used in regimen of insulin therapy, including medium or long-acting insulin or an analogue of basal insulin, and can be used simultaneously with oral hypoglycemic agents.

Dose of the drug Epidera^® select and adjust individually.

Special categories of patients.

Patients with impaired renal function. The pharmacokinetic properties of insulin glulisin are generally preserved in patients with impaired renal function. However, with impaired renal function, the need for insulin may decrease (see Pharmacokinetics).

Patients with impaired liver function. The pharmacokinetic properties of insulin glulisin have not been studied in patients with impaired liver function. In patients with impaired liver function, the need for insulin may be less due to a decrease in gluconeogenesis and the ability of insulin to be metabolized.

Elderly patients. Available data on the pharmacokinetics of insulin in elderly patients with diabetes mellitus are insufficient. Deteriorating renal function may lead to a decrease in insulin requirements.

Children and teens. There is no reliable clinical information on the use of the drug Epidera^® in children under the age of 6 years.

Application. The drug Epidera^® should be administered by sc injection shortly (0-15 minutes) before or immediately after a meal or by continuous sc infusion using an insulin pump.

The drug Epidera^® apply s / c in the abdominal wall, thigh or deltoid muscle or by continuous infusion under the skin of the anterior abdominal wall.Places for injection or infusion in the injection zone (the anterior wall of the abdominal cavity, thighs or deltoid muscle) should be changed alternately. The degree of absorption and, probably, the onset and duration of action may depend on the specific injection site, technique of its implementation and other indicators. Subcutaneous injection into the abdominal wall provides faster absorption than administration of the drug to other injection sites.

Care must be taken not to damage the blood vessels. After administration of the drug should not be massaged injection site. Patients should be taught the correct injection technique.

Mix with other insulins. Insulin glulisin should not be mixed with drugs other than human insulin NPH (Neutral Protamine Hagedorn).

Instructions for use^®

Before the first use, the syringe pen should be kept at room temperature for 1-2 hours.

Check cartridge before use. It can be used only when the solution in it is transparent, colorless, without visible solid particles and has the same consistency as water, since Epidera is a solution that does not require resuspension before use.

Empty syringe pens cannot be used again, they should be disposed of properly.

To prevent infection, each prefilled syringe pen must be used by only one person. Before each injection, check the information on the label to avoid the erroneous administration of other insulins instead of insulin glulisin (see SPECIAL INSTRUCTIONS).

Important information on using the SoloStar Syringe Pen

• For each injection, use a new needle compatible only with the SoloStar syringe pen. Do not select a dose or press the injection button if the needle is not attached to the syringe pen.
• Perform a safety test before each injection.
• The pen is intended for one patient only and should not be shared with others.
• If another person is injecting, that person must take special safety measures to prevent accidents involving the use of a needle and infection.
• Do not use the SoloStar syringe pen in case of damage or if there are doubts about its correct functioning.
• It is always necessary to have a spare SoloStar syringe pen in case of loss or damage.

Storage instructions

Carefully read the information on the storage of the SoloStar syringe pen.

If the SoloStar syringe pen is stored in the refrigerator, remove it from there 1–2 hours before administering the drug so that it warms up to room temperature. Injecting chilled insulin is more painful.

Used Syringe Pen Epidera^® subject to destruction in accordance with established rules.

Exploitation

Protect the SoloStar syringe pen from dust and dirt.

You can clean the outside of the SoloStar syringe pen by wiping it with a damp cloth.

Do not immerse in liquid, do not rinse or lubricate the syringe pen, as this may damage it.

The SoloStar syringe pen is designed for accurate and safe operation.

It must be used with caution. Avoid situations where the pen may be damaged. If you suspect that Epidera^® damaged, use a new syringe pen.

Stage 1. Insulin control.

A. Carefully read the label on the syringe pen instance to ensure proper insulin is injected. Epidera^® gray with a purple button for injecting.

B. Remove the cap of the syringe pen.

C. Monitor the appearance of insulin. Lantus is a transparent insulin. Do not use the Epidera Syringe Pen^®if the insulin is cloudy, colored or has foreign particles.

Stage 2. Attaching the needle.

Always use a new sterile needle for each injection.This will help prevent contamination as well as possible clogging of the needle.

A. Remove the protective label from the needle container.

B. Set the needle in line with the syringe pen, and then hold it on a straight line until it is attached (screwed on or inserted depending on the type of needle).

• If the needle is not in line with the syringe pen at the time of attachment, this can lead to a violation of the insulating layer of rubber and cause fluid leakage or fracture of the needle.

Stage 3. Security Test.

In all cases, perform a safety test before each injection. This ensures that the exact dose is obtained using the following:

• a guarantee that the syringe pen and needle function correctly;
• remove air bubbles.

A. Measure a dose of 2 units by rotating the metering selector.

B. Remove the outer cap of the needle and store it, then put the needle used after the injection was inserted into it. Remove the inner cap of the needle and discard it.

C. Place the pen with the needle up.

D. Use your fingertips to gently tap the insulin container so that all air bubbles rise up to the needle.

E. Press the injection button all the way. Check if insulin appears on the tip of the needle.

You can conduct safety tests several times until insulin appears.

• If insulin does not appear, check for air bubbles and retest the safety tests 2 more times before removing them.
• If insulin is not observed, this may be due to clogging of the needle. Replace the needle and repeat the test.
• If the appearance of insulin is not observed after replacing the needle, the syringe pen may be damaged. Do not use it.

Stage 4. Dose Selection.

You can set the dose with an accuracy of 1 unit (from a minimum dose of 1 unit to a maximum of 80 units). If a dose exceeding 80 units is required, 2 or more injections must be given.

A. Check that the dosing window reads “0” after completing the safety test.

B. Select the required dose. If a dose that is higher than necessary is set, the dosage selector should be returned to its original position.

• Do not press the injection button while rotating the selector, otherwise insulin will leak.
• It is not possible to return the metering selector to a number of units that exceeds the amount that remains in the syringe pen. Do not try to force the dosing selector back. In this case, you should either enter the remainder of the insulin glargine and supplement the necessary dose with a new syringe pen, or use a new Epidera^® for the introduction of a full dose.

Stage 5. Technique for the injection.

A. Adhere to the injection technique, which the doctor will familiarize the patient.

B. Insert the needle into the skin.

C. Enter the dose by pressing the injection button all the way. After the injection is introduced, a “0” should be set in the dosing window.

D. Leave the injection button down. Slowly count to 10 before removing the needle from the skin. This ensures the introduction of a full dose.

Stage 6. Removal and disposal of the needle.

In all cases, remove the needle after each injection and store the syringe pen without the needle attached. This provides prevention:

• contamination and / or infection;
• air entering the insulin container and insulin leakage, which can lead to improper dosing.

A. Put the outer needle cap back on the needle and use it to twist the needle from the syringe pen. To reduce the risk of accidents involving the use of the needle, never put the inner cap of the needle back on.

B. If the injection was given by another person, they must take special measures when removing and disposing of the needle (for example, the technique of closing the cap with one hand) to reduce the risk of accidents involving the use of the needle, as well as the spread of infectious diseases.

B.Dispose of the needle carefully (in accordance with established instructions).

C. In all cases, close the syringe pen with a cap and store the syringe pen for the next injection.

Contraindications

Hypersensitivity to insulin glulisin or other components of the drug, hypoglycemia.

Side effects

The most common side effect of insulin therapy is hypoglycemia, which occurs as a result of an overdose of insulin.

The following are the side effects observed during clinical trials (common (1/10); ordinary (1/1001/10), unusual (1/10001/100), rare (1/10 0001/1000), exceptional (1 / 10 000); unknown (it is not possible to estimate according to the available data)).

In each group, according to the frequency of occurrence, side effects are given in order of decreasing severity.

Metabolic and nutritional disorders. Symptoms of hypoglycemia usually occur suddenly. These include cold sweat, pallor of the skin, increased fatigue, nervousness or tremors, anxiety, unusual tiredness or weakness, impaired attention, drowsiness, severe hunger, blurred vision, headache, nausea, and a strong heartbeat. Hypoglycemia can reach a significant degree and lead to loss of consciousness and / or seizures and cause temporary or permanent impairment of brain function or even cause death.

On the part of the skin and subcutaneous tissues. Local hypersensitivity reactions (redness, swelling and itching at the injection site) are possible with insulin treatment. Such reactions are usually transient and usually disappear with continued treatment.

Lipodystrophy can occur at the injection site as a result of non-compliance with the procedure for changing the injection site.

Violation of the general condition and reaction at the injection site. Systemic hypersensitivity reactions may include hives, chest tightness, shortness of breath, allergic dermatitis, and pruritus. Severe cases include a generalized allergic reaction along with an anaphylactic reaction, which can be life threatening.

special instructions

Transfer of the patient to the use of a new insulin preparation should be carried out under medical supervision. a change in the strength of the action, type of drug (manufacturer), type of drug (normal, npc, insulin tape), type (animal origin) and / or production method may require adjustment of the dose of insulin.

It may also be necessary to regulate the concomitant use of oral antidiabetic drugs.

Hyperglycemia. The use of inadequate doses or termination of treatment, especially in patients with insulin-dependent diabetes mellitus, can lead to the development of potentially lethal conditions - hyperglycemia and diabetic ketoacidosis.

Hypoglycemia. Hypoglycemia occurs depending on the profile of action of insulin that is used, and may change with the transition to a new treatment regimen.

Conditions that may make the early symptoms of hypoglycemia atypical or less pronounced include a significant duration of diabetes, intensive insulin therapy, diabetic neuropathy, the use of drugs such as beta-adrenergic receptor blockers, or a switch from animal insulin to human insulin. The need for dose adjustment can also occur with increased physical activity or a change in the usual diet.Exercise immediately after eating increases the risk of hypoglycemia.

Hypoglycemia after injection of fast-acting insulin analogues usually occurs earlier than with the use of soluble human insulin. Hypoglycemic or hyperglycemic reactions, if the patient is not adequately assisted, can lead to loss of consciousness, coma, or death.

The need for insulin may change if there is another illness or emotional disturbance.

There were reports of erroneous administration of drugs when other insulins, in particular long-acting insulins, were accidentally administered instead of insulin glulisin. Before each injection, check the information on the cartridge label to avoid mistyping other insulins instead of insulin.

One dose of this drug contains less than 1 mmol (23 mg) of sodium, that is, it contains virtually no sodium.

Epidera contains m-cresol, which can cause allergic reactions.

The combination of Epaidra with pioglitazone. Cases of heart failure have been reported with pioglitazone in combination with insulin;