Aminargin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMINARGIN (AMINARGIN)

Composition:

Active substance: L-arginini hydrochloridum;

1 ml of solution contains 42 mg of arginine hydrochloride;

Excipient: water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear colorless or slightly yellowish-brown solution. Theoretical osmolarity 398 mOsm/L.

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Pharmacotherapeutic group. Blood substitutes and perfusion solutions. Additional 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 significant protective effects under critical conditions.

Arginine demonstrates anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, free radical-scavenging, and detoxifying activities. It functions as 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 enhancing the conversion of ammonia into urea. It exerts hepatoprotective effects due to its antioxidant, anti-hypoxic, and membrane-stabilizing activities and positively influences energy supply processes in hepatocytes.

Arginine serves as a substrate for nitric oxide synthase (NOS), the enzyme catalyzing nitric oxide (NO) synthesis in endotheliocytes. The drug activates guanylate cyclase and increases the level of cyclic guanosine monophosphate (cGMP) in vascular endothelium. It reduces activation and adhesion of leukocytes and platelets to the vascular endothelium, suppresses 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. Arginine additionally suppresses the synthesis of asymmetric dimethylarginine (ADMA), a powerful endogenous inducer of oxidative stress. The drug 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 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 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 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 the drug, it should be taken into account that it may cause pronounced and persistent hyperkalemia against the background of renal insufficiency in patients taking or previously taking 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.

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

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

Caution is advised in patients with electrolyte metabolism disorders and 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.

100 ml of solution contains 20 mmol of arginine and 20 mmol of chloride.

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 affect 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 medicinal product is 100 ml of solution.

In severe circulatory disorders affecting central and peripheral vessels, as well as in pronounced symptoms of intoxication, hypoxia, and asthenic conditions, the dose may be increased 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 dose of the medicinal product is 5–10 ml 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 begin 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 supportive therapy to maintain 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.

Adverse Reactions

General disorders: hyperthermia, feeling of warmth, body aches.

Musculoskeletal system: joint pain.

Gastrointestinal tract: dry mouth, nausea, vomiting.

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

Immune system: anaphylactic shock, hypersensitivity reactions, including rash, urticaria, angioneurotic edema.

Respiratory, thoracic and mediastinal system: dyspnea.

Cardiovascular system: fluctuations in blood pressure, changes in heart rate, chest pain.

Nervous system: headache, dizziness, feeling of fear, weakness, seizures, tremor, more frequent when the infusion rate is exceeded.

Laboratory findings: hyperkalemia.

Reporting suspected adverse reactions.

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

Shelf life: 2 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; 1 bottle per carton.

Prescription status. Prescription only.

Manufacturer: Limited Liability Company "Novofarm-Biosyntez".

Manufacturer's address and location of business activity.

38, Zhytomyrska Street, city of Zviahel, Zviahel district, Zhytomyr region, 11700, Ukraine.