Angio-betargin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Angio-Betargin (ANGIO- BETARGIN)

Composition:

Active substance: arginine hydrochloride;

1 bottle (100 ml of solution) contains: arginine hydrochloride – 4.2 g;

Excipient: water for injections.

Ionic composition per 1000 ml of the preparation: C6H14N4O2 – 200 mmol; Cl- – 200 mmol.

Pharmaceutical form. Solution for infusion.

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

Pharmacotherapeutic group. Plasma 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 exerts significant protective effects under critical conditions.

Arginine demonstrates anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, anti-radical, and detoxifying activities. It acts 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 action due to its antioxidant, anti-hypoxic, and membrane-stabilizing properties and positively influences energy supply processes in hepatocytes.

Arginine serves as a substrate for nitric oxide synthase (NOS), the enzyme that catalyzes the production of nitric oxide (NO) in endothelial cells. The drug activates guanylate cyclase and increases the level of cyclic guanosine monophosphate (cGMP) in vascular endothelium. It reduces the 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. Additionally, arginine suppresses the synthesis of asymmetric dimethylarginine—an endogenous stimulator of oxidative stress. The drug stimulates thymus gland activity, which produces T-cells, and helps regulate 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 heart 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 kidney function, hyperchloremic acidosis; history of allergic reactions; use of potassium-sparing diuretics, as well as spironolactone. Myocardial infarction (including in medical history).

Interaction with other medicinal products and other types of interactions.

When using Angio-Betargin, 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 increase insulin levels in the blood.

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.

Angio-Betargin should be used with caution in patients with endocrine gland dysfunction. This 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 and kidney diseases. If symptoms of asthenia worsen during treatment with this medicinal product, therapy should be discontinued.

The drug should be used cautiously in patients with angina pectoris.

Use during pregnancy or breastfeeding.

The drug 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 drug during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage.

The drug should be administered intravenously by drip infusion at a rate of 10 drops per minute for the first 10–15 minutes, after which 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 disturbances in central and peripheral vessels, pronounced signs 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 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 begin with half of the calculated dose. Any additional correction should be performed after obtaining updated acid-base balance results.

Children.

The drug may be used in children aged 3 years and older.

Overdose.

Symptoms: renal failure, hypoglycemia, metabolic acidosis.

Treatment. In case of overdose, the infusion of the drug must be discontinued. Monitoring of physiological responses and supportive therapy to maintain vital functions should be performed. 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.

General disorders: hyperthermia, hot flushes, malaise.

Musculoskeletal system disorders: joint pain.

Gastrointestinal disorders: dry mouth, nausea, vomiting.

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

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

Respiratory, thoracic and mediastinal disorders: dyspnea.

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

Nervous system disorders: headache, dizziness, fear sensation, weakness, seizures, tremor, more frequent when the infusion rate exceeds recommended.

Laboratory investigations: hyperkalemia.

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

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

Keep out of reach of children.

Incompatibility. The drug is incompatible with thiopental.

Packaging. 100 ml of solution in a bottle No. 1 in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Infuziya".

Manufacturer's address and location of business activity.

84A Nemirovskе Highway, village Vinnitski Khutory, Vinnitsa district, Vinnitsa region, 23219, Ukraine.

Marketing Authorization Holder. LLC "WORWARDS PHARMA".

Address of the Marketing Authorization Holder.

4 Akademika Krzhyzhanivskoho Street, Kyiv, 03142, Ukraine.