Arginex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARGINEKS (ARGINEX)

Composition:

Active substance: arginine hydrochloride (arginine hydrochloride);

1 ml of concentrate for infusion solution contains 420 mg of arginine hydrochloride (in 10 ml of concentrate contains 20 mmol of arginine and 20 mmol of chloride ions);

Excipient: water for injections.

Pharmaceutical form. Concentrate for infusion solution.

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

Pharmacotherapeutic group. Blood 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 in the body and exhibits important protective effects under critical conditions.

The medicinal product Arginenex demonstrates anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, free radical-scavenging, and detoxifying activities. It functions as an active regulator of intermediate metabolism and energy production 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 enhancing the conversion of ammonia into urea. It exerts hepatoprotective action due to its antioxidant, anti-hypoxic, and membrane-stabilizing properties and positively influences energy metabolism in hepatocytes.

Arginine serves as a substrate for NO synthase—an enzyme that catalyzes the production of nitric oxide (NO) in endothelial cells. It activates guanylate cyclase and increases the level of cyclic guanosine monophosphate (cGMP) in vascular endothelium, thereby reducing leukocyte and platelet activation and adhesion to the vascular endothelium. It suppresses the synthesis of adhesion proteins VCAM-1 and MCP-1, thus 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. Additionally, arginine suppresses the synthesis of asymmetric dimethylarginine—a powerful endogenous stimulator of oxidative stress. Arginine stimulates thymus gland activity, which produces T-cells, and regulates blood glucose levels during physical exertion. It exerts an acidifying effect and contributes to the correction of acid-base balance.

Pharmacokinetics

During continuous intravenous infusion, the maximum plasma concentration of arginine hydrochloride is reached within 20–30 minutes after the start of administration. Arginine 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 intermittent claudication, diabetic angiopathy, arterial hypertension, chronic heart failure, hypercholesterolemia, chronic obstructive pulmonary diseases, pulmonary hypertension, fetal growth retardation and preeclampsia — use the medicinal product as part of combination therapy.

Contraindications

Hypersensitivity to the medicinal product. Severe renal function impairment, hyperchloremic acidosis; history of allergic reactions; use of potassium-sparing diuretics, as well as spironolactone. Myocardial infarction (including history of).

Interaction with other medicinal products and other forms of interaction

When using arginine, it should be considered that it may cause pronounced and persistent hyperkalemia in patients with renal insufficiency 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 infusion, as the medicinal product may contribute to the development of hyperkalemia.

Arginine should be used with caution in patients with endocrine gland dysfunction. The medicinal product may stimulate insulin and growth hormone secretion. If dry mouth occurs, blood glucose levels should be checked.

Use with caution in patients with electrolyte metabolism disorders or kidney diseases. If symptoms of asthenia worsen during treatment with the medicinal product, therapy should be discontinued.

The medicinal product should be used cautiously 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 on the use of arginine in women during breastfeeding.

Ability to influence reaction rate 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 contents of 1 ampoule (10 ml concentrate for infusion solution) should be diluted in 100 ml of diluent such as 0.45% sodium chloride solution or water for injections before administration.

After dilution, the medicinal product should be administered intravenously by slow 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 diluted medicinal product is 100 ml.

In cases of severe circulatory disturbances in central and peripheral vessels, pronounced intoxication, hypoxia, or asthenic conditions, the dose of the diluted medicinal product may be increased up to 200 ml per day.

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

The dose for children under 12 years of age is 5–10 ml of the diluted medicinal product per kg of body weight per day.

For the 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 results.

Children. The medicinal product may be used in 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 alkalinizing agents and diuretics, as well as electrolyte solutions (0.9% sodium chloride solution, 5% glucose solution). Treatment is symptomatic.

Adverse Reactions

All adverse reactions are listed by organ systems.

Frequency is defined according to the following categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from the available data).

Immune system disorders: anaphylactic shock, hypersensitivity reactions, including rash, urticaria, angioedema.

Cardiovascular system disorders: frequency not known: hyperemia, fluctuations in blood pressure, changes in heart rhythm, chest pain.

Respiratory, thoracic and mediastinal disorders: dyspnea.

Nervous system disorders: frequency not known: headache, dizziness, fear sensation, weakness, seizures, tremor — more frequently when the infusion rate is exceeded.

Gastrointestinal disorders: very common: nausea, vomiting; frequency not known: dry mouth, abdominal pain.

Musculoskeletal and connective tissue disorders: joint pain.

Skin and subcutaneous tissue disorders: injection site reactions, including hyperemia, itching sensation, pallor of the skin, up to acrocyanosis.

Laboratory investigations: frequency not known: hyperkalemia.

General disorders and administration site conditions: hyperthermia, feeling of warmth, malaise.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life: 2 years.

Storage conditions

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach and sight of children.

Incompatibilities

The medicinal product must not be mixed with other medicinal products. Use only the solvents recommended in the section "Method of administration and dosage".

Packaging

10 ml in an ampoule. 3 or 5 ampoules per blister pack in a cardboard box.

Prescription status: Prescription-only medicine.

Manufacturer: Abhil Laboratories Private Limited.

Manufacturer's address and location of operations

Village Bhagwanpur, Tehsil Dera Bassi, District Sahibzada Ajit Singh Nagar, Punjab – 140507, India.