ARGILIFE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARGYLIFE (ARGILIFE)

Composition:

Active substance: arginine hydrochloride;

1 ml contains arginine hydrochloride — 42 mg;

Excipient: water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless or slightly yellowish-brown liquid.

Pharmacotherapeutic group.

Plasma substitutes and perfusion solutions. Supplementary solutions for intravenous administration. Amino acids. Arginine hydrochloride.

ATC code B05X B01.

Pharmacological Properties

Pharmacodynamics

Arginine (α-amino-δ-guanidinovaleric acid) is an amino acid belonging to the class of conditionally essential amino acids. It acts as an active and versatile cellular regulator of numerous vital functions of the organism and demonstrates important protective effects under critical conditions.

Arginine exhibits anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, anti-radical, and detoxifying activities. It is an active regulator of intermediate metabolism and energy supply processes and plays a role in maintaining hormonal balance in the body. It is known that arginine increases blood levels of insulin, glucagon, growth hormone, and prolactin. It participates in the synthesis of proline, polyamines, and agmatine, is involved in fibrinogenolysis and spermatogenesis, and exerts membrane-depolarizing effects.

Arginine is one of the main substrates in the urea synthesis cycle in the liver. The drug's hypoammonemic effect is achieved by activating the conversion of ammonia into urea. It exerts hepatoprotective action due to its antioxidant, anti-hypoxic, and membrane-stabilizing activities and positively influences energy supply processes in hepatocytes.

Argilayf is a substrate for NO-synthase—an enzyme that catalyzes the synthesis of nitric oxide in endotheliocytes. The drug activates guanylate cyclase and increases the level of cyclic guanosine monophosphate (cGMP) in vascular endothelium, reduces activation and adhesion of leukocytes and platelets to the vascular endothelium, inhibits the synthesis of adhesion proteins VCAM-1 and MCP-1, thereby preventing the formation and progression of atherosclerotic plaques. It also inhibits the synthesis of endothelin-1, a potent vasoconstrictor and stimulator of vascular smooth muscle cell proliferation and migration. Argilayf additionally suppresses the synthesis of asymmetric dimethylarginine—a powerful endogenous stimulator of oxidative stress. The medicinal product stimulates thymus gland activity, which produces T-cells, and regulates blood glucose levels during physical exertion. It exerts an acidifying effect and promotes correction of acid-base balance.

Pharmacokinetics

During continuous intravenous infusion, the maximum plasma concentration of arginine hydrochloride is observed 20–30 minutes after the start of administration. Argilayf crosses the placental barrier, is filtered in the renal glomeruli, but is almost completely reabsorbed in the renal tubules.

Clinical characteristics.

Indications.

Metabolic alkalosis, hyperammonemia, atherosclerosis of cardiac and cerebral vessels, peripheral vascular atherosclerosis including manifestations of intermittent claudication, diabetic angiopathy, arterial hypertension, chronic heart failure, hypercholesterolemia, chronic obstructive pulmonary diseases, pulmonary hypertension, fetal growth retardation and preeclampsia — as part of complex therapy.

Contraindications.

Hypersensitivity to the drug. Severe impairment of renal function, hyperchloremic acidosis; history of allergic reactions; concomitant use of potassium-sparing diuretics, including spironolactone; myocardial infarction (including history of myocardial infarction).

Interaction with other medicinal products and other forms of interaction.

When using Argilayf, it should be taken into account that the drug may cause pronounced and persistent hyperkalemia against the background of renal insufficiency in patients who are taking or have taken spironolactone. Prior use of potassium-sparing diuretics may also contribute to increased blood potassium concentration. Concomitant use with aminophylline may lead to increased blood insulin levels.

Arginine is incompatible with thiopental.

Special precautions for use.

In patients with renal insufficiency, urine output and plasma potassium levels should be checked before starting the infusion, as the medicinal product may contribute to the development of hyperkalemia.

Argilife should be used with caution in patients with endocrine gland dysfunction. The medicinal product may stimulate insulin and growth hormone secretion.

When dry mouth occurs, blood glucose levels should be checked.

The medicinal product should be used with caution in patients with electrolyte imbalances and kidney diseases. If symptoms of asthenia worsen during treatment, therapy should be discontinued.

The medicinal product should be used with caution in patients with angina pectoris.

Use during pregnancy or breastfeeding.

The medicinal product crosses the placenta and therefore may be used during pregnancy only when the expected benefit to the mother outweighs the potential risk to the fetus.

There are no data available on the use of the medicinal product during breastfeeding.

Ability to influence reaction speed while driving or operating machinery.

Caution should be exercised when driving or operating machinery, as the medicinal product may cause dizziness.

Method of Administration and Dosage

The medicinal product should be administered intravenously by drip infusion at a rate of 10 drops per minute for the first 10–15 minutes; thereafter, the infusion rate may be increased to 30 drops per minute.

The daily dose of the drug is 100 ml of solution.

In severe circulatory disorders affecting central and peripheral blood vessels, as well as in pronounced intoxication, hypoxia, and asthenic conditions, the drug dose may be increased up to 200 ml per day.

The maximum infusion rate of the solution should not exceed 20 mmol/hour.

For children under 12 years of age, the drug dose is 5–10 ml per kg of body weight per day.

For treatment of metabolic alkalosis, the dose can be calculated as follows:

arginine hydrochloride (mmol)
---------------------------------------- × 0.3 × body weight (kg)
base excess (Be) (mmol/L)

Infusion should be initiated with half of the calculated dose. Any additional correction should be performed after obtaining updated acid-base balance test results.

Children

The medicinal product can be administered to children aged 3 years and older.

Overdose

Symptoms: renal failure, hypoglycemia, metabolic acidosis.

Treatment: In case of overdose, infusion of the medicinal product must be discontinued. Monitoring of physiological responses and maintenance of vital functions should be carried out. If necessary, administer alkalizing agents and diuretics, as well as electrolyte solutions (0.9% sodium chloride solution, 5% glucose solution). Symptomatic therapy is recommended.

Side effects.

General disorders: hyperthermia, feeling of warmth, malaise.

From the musculoskeletal system: joint pain.

From the gastrointestinal tract: dry mouth, nausea, vomiting.

From the skin and subcutaneous tissue: reactions at the injection site, including hyperemia, itching sensation, skin pallor, up to acrocyanosis.

From the immune system: anaphylactic shock, hypersensitivity reactions, including rash, urticaria, angioneurotic edema.

From the respiratory system, thoracic organs and mediastinum: dyspnea.

From the cardiovascular system: fluctuations in blood pressure, changes in heart rate, chest pain.

From the nervous system: headache, dizziness, feeling of fear, weakness, seizures, tremor—more frequently when the infusion rate exceeds recommended.

Laboratory findings: hyperkalemia.

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibility.

The medicinal product is incompatible with thiopental.

Packaging.

100 ml in a bottle or vial, 1 bottle or vial per carton.

Prescription category. Prescription only.

Manufacturer.

JSC "Halychpharm".

Manufacturer's address and location of business activity.

6/8 Opryshkovska Street, Lviv, 79024, Ukraine.