Sargin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SARGIN (SARGIN)

Composition:

Active substance: L-arginine hydrochloride (L-arginini hydrochloridum);

1 ml of solution contains 42 mg of L-arginine hydrochloride;

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. 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 demonstrates important protective effects under critical conditions.

Sargin exhibits anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, free radical-scavenging, and detoxifying activities. It functions as an active regulator of intermediary 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.

Sargin serves as a substrate for NO-synthase, 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, 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. Sargin additionally suppresses the synthesis of asymmetric dimethylarginine—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 contributes to the 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. Sargin 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 Sargin, 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 lead to increased potassium concentration in blood. Concomitant use with aminophylline may increase insulin levels in blood.

Arginine is incompatible with thiopental.

Special precautions.

100 ml contains 20 mmol of arginine and 20 mmol of chlorides.

In patients with renal insufficiency, diuresis and plasma potassium levels should be checked before starting infusion, as the drug may cause hyperkalemia.

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

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, 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; therefore, during pregnancy it should be used only when the expected benefit to the mother outweighs the potential risk to the fetus.

Data on the use of the drug during breastfeeding are lacking.

Ability to influence reaction rate when driving or operating machinery.

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

Administration and Dosage

The drug 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 affecting central and peripheral vessels, as well as in pronounced 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 daily dose is 5–10 ml per kg of body weight.

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 drug 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 drug must be discontinued. Monitoring of physiological responses and supportive therapy to maintain vital functions should be conducted. If necessary, administer alkalizing agents and diuretics to promote diuresis, 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.

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 system, thoracic organs and mediastinum: dyspnea.

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

Nervous system: headache, dizziness, feeling of fear, weakness, seizures, tremor, more frequent with exceeding the infusion rate.

Laboratory parameters: hyperkalemia.

Shelf life. 2 years.

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

Storage conditions.

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

Keep out of reach of children.

Incompatibility.

The medicinal product is incompatible with thiopental.

Packaging. 100 ml in a vial. 1 vial per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.