Humalog^® (Solution) Instructions for Use

ATC Code

A10AB04 (Insulin lispro)

Active Substance

Insulin lispro (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Short-acting human insulin analogue

Pharmacotherapeutic Group

Hypoglycemic agent – short-acting insulin analog

Pharmacological Action

A DNA-recombinant analogue of human insulin. It differs from the latter by the reversed sequence of amino acids at positions 28 and 29 of the B-chain of insulin.

The main action of the drug is the regulation of glucose metabolism. In addition, it has an anabolic effect. In muscle tissue, there is an increase in the content of glycogen, fatty acids, glycerol, an increase in protein synthesis and an increase in amino acid uptake, but at the same time, there is a decrease in glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism and amino acid release.

In patients with type 1 and type 2 diabetes mellitus, the use of insulin lispro results in a more significant reduction in postprandial hyperglycemia compared to soluble human insulin. For patients receiving short-acting and basal insulins, it is necessary to adjust the dose of both insulins to achieve optimal blood glucose levels throughout the day.

As with all insulin preparations, the duration of action of insulin lispro may vary in different patients or at different times in the same patient and depends on the dose, injection site, blood supply, body temperature and physical activity.

The pharmacodynamic characteristics of insulin lispro in children and adolescents are similar to those observed in adults.

In patients with type 2 diabetes mellitus receiving maximum doses of sulfonylurea derivatives, the addition of insulin lispro leads to a significant reduction in glycated hemoglobin.

Treatment with insulin lispro in patients with type 1 and type 2 diabetes mellitus is accompanied by a reduction in the number of episodes of nocturnal hypoglycemia.

The glucodynamic response to Insulin lispro is independent of renal or hepatic functional impairment.

Insulin lispro has been shown to be equimolar to human insulin, but its action is more rapid and of shorter duration.

Insulin lispro is characterized by a rapid onset of action (about 15 minutes) due to its high absorption rate, which allows it to be administered immediately before a meal (0-15 minutes before eating) unlike regular short-acting insulin (30-45 minutes before eating). Insulin lispro has a shorter duration of action (from 2 to 5 hours) compared to regular human insulin.

Pharmacokinetics

Absorption and Distribution

After subcutaneous administration, Insulin lispro is rapidly absorbed and reaches C_max in plasma within 30-70 minutes. The V_d of insulin lispro and regular human insulin are identical and are in the range of 0.26-0.36 L/kg.

Elimination

After subcutaneous administration, the T_1/2 of insulin lispro is about 1 hour. In patients with renal and hepatic impairment, the higher absorption rate of insulin lispro compared to regular human insulin is maintained.

Indications

• Diabetes mellitus in adults and children requiring insulin therapy to maintain normal glucose levels.

ICD codes

Dosage Regimen

Solution

The dose is determined individually by the doctor, depending on the patient’s needs. Humalog^® can be administered shortly before a meal, if necessary – immediately after a meal.

The temperature of the administered drug should be at room temperature.

Humalog^® is administered subcutaneously as injections or as a continuous subcutaneous infusion using an insulin pump. If necessary (ketoacidosis, acute illnesses, interoperative or postoperative period), Humalog^® can be administered intravenously.

Subcutaneous injections should be given in the shoulder, thigh, buttock or abdominal area. Injection sites should be rotated so that the same site is not used more than once a month. When administering Humalog^® subcutaneously, care must be taken to avoid the drug entering a blood vessel. After the injection, the injection site should not be massaged. The patient must be trained in the correct injection technique.

Rules for administering Humalog^®

Preparation for administration

The Humalog^® solution should be clear and colorless. Do not use a cloudy, thickened, or slightly colored solution, or if solid particles are visually detected in it.

When installing the cartridge into the pen-injector, attaching the needle, and performing the insulin injection, the manufacturer’s instructions supplied with each pen-injector must be followed.

Administration

1. Wash your hands.

2. Choose an injection site.

3. Disinfect the skin at the injection site with an antiseptic.

4. Remove the cap from the needle.

5. Secure the skin by stretching it or pinching a large fold. Insert the needle according to the pen-injector instructions for use.

6. Press the button.

7. Remove the needle and gently press the injection site for a few seconds. Do not rub the injection site.

8. Using the needle protective cap, unscrew the needle and destroy it.

9. Injection sites should be rotated so that the same site is used no more than approximately once a month.

Intravenous administration of insulin

Intravenous injections of Humalog^® should be performed in accordance with standard clinical practice for intravenous injections, e.g., intravenous bolus injection or using an infusion system. In this case, frequent monitoring of blood glucose levels is required.

Infusion systems with concentrations from 0.1 IU/ml to 1.0 IU/ml of insulin lispro in 0.9% sodium chloride solution or 5% dextrose solution are stable at room temperature for 48 hours.

Subcutaneous insulin infusion using an insulin pump

Minimed and Disetronic insulin infusion pumps can be used for Humalog^® infusion. It is necessary to strictly follow the instructions supplied with the pump. The infusion set is changed every 48 hours. Aseptic technique must be observed when connecting the infusion set. In case of a hypoglycemic episode, the infusion should be stopped until the episode resolves. If recurrent or very low blood glucose levels are noted, this should be reported to the doctor and a reduction or cessation of insulin infusion should be considered. Pump malfunction or infusion set blockage can lead to a rapid rise in glucose levels. If a disruption in insulin delivery is suspected, follow the instructions and inform the doctor if necessary. When using a pump, Humalog^® should not be mixed with other insulins.

Adverse Reactions

Side effect related to the main action of the drug hypoglycemia. Severe hypoglycemia can lead to loss of consciousness (hypoglycemic coma) and, in exceptional cases, death.

Allergic reactions local allergic reactions are possible – redness, swelling or itching at the injection site (usually disappear within a few days or weeks); systemic allergic reactions (occur less frequently but are more serious) – generalized itching, urticaria, angioedema, fever, shortness of breath, decreased blood pressure, tachycardia, increased sweating. Severe cases of systemic allergic reactions can be life-threatening.

Local reactions lipodystrophy at the injection site.

Contraindications

• Hypoglycemia;
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

To date, no adverse effects of insulin lispro on pregnancy or the health of the fetus/newborn have been identified. No relevant epidemiological studies have been conducted.

The goal of insulin therapy during pregnancy is to maintain adequate glucose control in patients with insulin-dependent diabetes mellitus or with gestational diabetes. The need for insulin usually decreases in the first trimester and increases in the second and third trimesters of pregnancy. During childbirth and immediately after, the need for insulin may sharply decrease.

Women of childbearing age with diabetes should inform their doctor of an occurred or planned pregnancy. During pregnancy, patients with diabetes require careful monitoring of blood glucose levels, as well as general clinical monitoring.

In patients with diabetes during breastfeeding, adjustment of the insulin dose and/or diet may be required.

Use in Hepatic Impairment

The need for insulin may decrease in hepatic insufficiency.

In patients with hepatic impairment, the higher absorption rate of insulin lispro compared to regular human insulin is maintained.

Use in Renal Impairment

The need for insulin may decrease in renal insufficiency.

In patients with renal impairment, the higher absorption rate of insulin lispro compared to regular human insulin is maintained.

Special Precautions

Transferring a patient to another type or another brand of insulin should be carried out under strict medical supervision. Changes in potency, brand (manufacturer), type (e.g., Regular, NPH, Lente), species (animal, human, human insulin analogue) and/or method of manufacture (DNA-recombinant insulin or animal insulin) may necessitate a dose change.

Conditions in which the early warning symptoms of hypoglycemia may be nonspecific and less pronounced include long-standing diabetes, intensive insulin therapy, diabetic neuropathy, or the use of medications such as beta-blockers.

In patients with hypoglycemic reactions after switching from animal insulin to human insulin, the early symptoms of hypoglycemia may be less pronounced or different from those they experienced with their previous insulin. Uncorrected hypoglycemic or hyperglycemic reactions can cause loss of consciousness, coma, or death.

The use of inadequate doses or discontinuation of treatment, especially in insulin-dependent diabetes mellitus, can lead to hyperglycemia and diabetic ketoacidosis, conditions that are potentially life-threatening.

The need for insulin may decrease in patients with renal insufficiency, as well as in patients with hepatic insufficiency due to reduced gluconeogenesis and insulin metabolism. However, in patients with chronic hepatic insufficiency, increased insulin resistance may lead to an increased need for insulin.

The need for insulin may increase during infectious diseases, emotional stress, or with an increase in the amount of carbohydrates in the diet.

Dose adjustment may also be required if the patient increases physical activity or changes their usual diet. Exercise immediately after a meal increases the risk of hypoglycemia. As a consequence of the pharmacodynamics of rapid-acting insulin analogues, if hypoglycemia develops, it may occur earlier after injection than with soluble human insulin.

The patient should be warned that if the doctor has prescribed an insulin preparation with a concentration of 40 IU/ml in a vial, then insulin should not be drawn from a cartridge with an insulin concentration of 100 IU/ml using a syringe for insulin with a concentration of 40 IU/ml.

If it is necessary to take other medications simultaneously with Humalog^®, the patient should consult a doctor.

Effect on ability to drive vehicles and operate machinery

In hypoglycemia or hyperglycemia associated with an inadequate dosage regimen, the ability to concentrate and the speed of psychomotor reactions may be impaired. This can be a risk factor in potentially hazardous activities (including driving a vehicle or operating machinery).

Patients should exercise caution to avoid hypoglycemia while driving a vehicle. This is especially important for patients who have reduced or absent awareness of the warning symptoms of hypoglycemia, or who experience frequent episodes of hypoglycemia. Under these circumstances, the advisability of driving a vehicle should be assessed. Patients with diabetes can self-treat perceived mild hypoglycemia by taking glucose or high-carbohydrate food (it is recommended to always carry at least 20 g of glucose). The patient should inform the attending physician about any experienced hypoglycemia.

Overdose

Symptoms hypoglycemia, accompanied by the following symptoms: lethargy, increased sweating, tachycardia, headache, vomiting, confusion.

Treatment mild states of hypoglycemia are usually relieved by oral administration of glucose or other sugar, or sugar-containing products.

Correction of moderate hypoglycemia can be done by intramuscular or subcutaneous administration of glucagon followed by oral carbohydrate intake after the patient’s condition stabilizes. Patients who do not respond to glucagon are administered an intravenous solution of dextrose (glucose).

If the patient is in a coma, glucagon should be administered intramuscularly or subcutaneously. In the absence of glucagon or if there is no response to its administration, an intravenous solution of dextrose (glucose) must be administered. Immediately after regaining consciousness, the patient must be given a carbohydrate-rich meal.

Further maintenance carbohydrate intake and observation of the patient may be required, as a recurrence of hypoglycemia is possible.

Drug Interactions

The hypoglycemic effect of Humalog^® is reduced by oral contraceptives, corticosteroids, thyroid hormone preparations, danazol, beta₂-adrenergic agonists (including ritodrine, salbutamol, terbutaline), tricyclic antidepressants, thiazide diuretics, chlorprothixene, diazoxide, isoniazid, lithium carbonate, nicotinic acid, phenothiazine derivatives.

The hypoglycemic effect of Humalog^® is enhanced by beta-blockers, ethanol and ethanol-containing preparations, anabolic steroids, fenfluramine, guanethidine, tetracyclines, oral hypoglycemic drugs, salicylates (e.g., acetylsalicylic acid), sulfonamides, MAO inhibitors, ACE inhibitors (captopril, enalapril), octreotide, angiotensin II receptor antagonists.

Humalog^® should not be mixed with animal insulin preparations.

Humalog^® can be used (under medical supervision) in combination with longer-acting human insulin or in combination with oral sulfonylurea hypoglycemic agents.

Storage Conditions

List B. The drug should be stored out of the reach of children, in a refrigerator, at a temperature from 2°C (35.6°F) to 8°C (46.4°F); do not freeze; shelf life – 2 years.

The drug in use should be stored at room temperature from 15°C (59°F) to 25°C (77°F); protect from direct sunlight and heating; shelf life – no more than 28 days.

Dispensing Status

The drug is dispensed by prescription.

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.