Angio-betargin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Angio-Betargin

Composition:

active substance: arginine hydrochloride;

1 ml of solution 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 exhibits important protective effects under critical conditions.

Arginine hydrochloride possesses anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, anti-radical, and detoxifying activities. It acts 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 and is involved in fibrinogenolysis and spermatogenesis. It also 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 activities and positively influences energy supply processes in hepatocytes.

Arginine hydrochloride serves as 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, and 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. Arginine hydrochloride additionally suppresses the synthesis of asymmetric dimethylarginine—a powerful endogenous stimulator 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 aids in correcting acid-base balance.

Pharmacokinetics

With continuous intravenous infusion, maximum plasma concentration of arginine hydrochloride is observed 20–30 minutes after the start of administration. Arginine hydrochloride 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 the heart 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 — apply 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, including spironolactone. Myocardial infarction (including in medical history).

Interaction with other medicinal products and other forms of interaction

When using arginine, it should be taken into account that it 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. Concurrent 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 promote the development of hyperkalemia.

The drug 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.

Caution is advised when using the drug in patients with electrolyte metabolism disorders and kidney diseases. If symptoms of asthenia worsen during treatment, therapy should be discontinued.

The drug should be used with caution 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 medicinal product during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

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

Administration and Dosage

The medicinal product is 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 disturbances in central and peripheral vessels, pronounced signs of intoxication, hypoxia, and asthenic conditions, the 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 daily dose is 5–10 ml per kg of body weight.

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 results of the updated acid-base balance.

Children

The medicinal product is indicated for use 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 performed. If necessary, administer alkalizing agents and diuretics (saluretics), electrolyte solutions (0.9% sodium chloride solution, 5% glucose solution). Symptomatic therapy is recommended.

Adverse Reactions

General disorders: hyperthermia, feeling of warmth, malaise.

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, angioedema.

Respiratory system, thoracic organs and mediastinum: 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 infusion rate exceeds recommended.

Laboratory findings: hyperkalemia.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions

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

Keep out of reach and sight of children.

Incompatibilities. The medicinal product is incompatible with thiopental.

Packaging. 100 ml in a polypropylene container; 1 container per cardboard box.

Prescription status. Prescription only.

Manufacturer. Subsidiary enterprise "Farmatreyd".

Manufacturer's address

Sambirska St., 85, Drohobych, Lviv region, Ukraine.

Marketing Authorization Holder.

LLC "VORWARTS PHARMA".

Address of Marketing Authorization Holder.

4 Omelyan Prytsaka St., Kyiv, 03142, Ukraine.