Cordagin

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

Composition:

Active substance: arginine hydrochloride;

100 ml of solution contain arginine hydrochloride 4.2 g (in 1000 ml there are 200 mmol of arginine and 200 mmol of chlorides);

Excipient: water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless or slightly yellowish-brown liquid; theoretical osmolarity — 398 mosmol/L; pH 5.0–6.5.

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 in the body and demonstrates important protective effects under critical conditions.

Arginine exhibits anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, free radical scavenging, and detoxifying activities. It acts as a potent regulator of intermediary 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 production processes in hepatocytes.

Arginine serves as a substrate for NO synthase—the enzyme catalyzing nitric oxide (NO) synthesis in endotheliocytes. The drug activates guanylate cyclase and increases levels 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 further suppresses the synthesis of asymmetric dimethylarginine—a powerful endogenous stimulator of oxidative stress. The drug stimulates thymus gland activity, which produces T-cells, regulates blood glucose levels during physical exertion, and exerts an acidifying effect, thus contributing to the correction of acid-base balance.

Pharmacokinetics

During continuous intravenous infusion, maximum plasma concentration of arginine hydrochloride is observed 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 — as part of complex therapy.

Contraindications.

Hypersensitivity to the components of the drug. Severe renal function impairment, hyperchloremic acidosis; history of allergic reactions; concomitant use of potassium-sparing diuretics, including spironolactone. Myocardial infarction (including history of).

Interaction with other medicinal products and other forms of interaction.

When using the medicinal product Cordagin, it should be taken into account that it may cause pronounced and persistent hyperkalemia against the background of renal insufficiency in patients taking or having taken spironolactone. Prior use of potassium-sparing diuretics may also lead to increased blood potassium concentration. Concomitant use with aminophylline may increase insulin levels in 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 initiating infusion, as the medicinal product may cause hyperkalemia.

The drug 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.

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

There is no data available regarding the use of the drug during breastfeeding.

Ability to influence reaction rate while 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 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 up to 200 ml per day.

The maximum infusion rate must 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.

In 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 is indicated for 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. Physiological responses should be monitored and vital functions supported. If necessary, administer alkalizing agents and diuretics (saluretics), 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: 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 blood pressure, changes in heart rhythm, chest pain.

Nervous system: headache, dizziness, fear sensation, weakness, seizures, tremor, more frequent with infusion rate exceeding recommended.

Laboratory findings: hyperkalemia.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the drug. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Incompatibility. The drug is incompatible with thiopental.

Packaging. 100 ml in a bottle; 1 bottle per carton.

Prescription category. Prescription only.

Manufacturer. Private Joint-Stock Company "Infuziya".

Manufacturer's address and location of operations.
84A Nemyrivske Highway, Vinnytski Khytory, Vinnytsia district, Vinnytsia region, 23219, Ukraine.