Primagen

INSTRUCTIONS for medical use of the medicinal product PRIMEARGIN (PRIMEARGIN)

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 solution.

­­­­

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 and acts as an active and versatile cellular regulator of numerous vital functions of the body, exhibiting important 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 certain role in maintaining hormonal balance in the body. It is known that arginine increases blood levels of insulin, glucagon, growth hormone, and prolactin, 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 activating 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 is a substrate for NO-synthase, the enzyme catalyzing nitric oxide 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. Arginine 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 promotes correction of 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 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 manifestations of intermittent claudication, diabetic angiopathy, arterial hypertension, chronic heart failure, hypercholesterolemia, chronic obstructive pulmonary diseases, pulmonary hypertension, fetal growth restriction 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 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 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 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.

The medicinal product should be used with caution in patients with electrolyte imbalances and kidney disorders. If symptoms of asthenia worsen during treatment, therapy should be discontinued.

The medicinal product should be used with caution 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.

Dosage and Administration

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 blood vessels, pronounced intoxication, hypoxia, and asthenic conditions, the dose of the medicinal product 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 of the medicinal product 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.

Do not use any remaining medicinal product.

Children

The medicinal product may be administered to children aged 3 years and older.

Overdose

Symptoms: renal failure, hypoglycemia, metabolic acidosis.

Treatment: In case of overdose, the infusion of the medicinal product must be discontinued. Physiological responses should be monitored and vital functions supported. If necessary, administer alkalinizing agents and diuretics (saluretics), as well as electrolyte solutions (0.9% sodium chloride solution, 5% glucose solution). Treatment is symptomatic.

Side effects

General disorders: hyperthermia, feeling of warmth, 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, feeling of fear, weakness, seizures, tremor, more frequently observed when the infusion rate is exceeded.

Laboratory findings: hyperkalemia.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are encouraged to report all cases of suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: 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.

Incompatibilities

The medicinal product is incompatible with thiopental.

Packaging

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

Prescription status: Prescription only.

Manufacturer: Limited liability company "Novofarm-Biosyntez".

Manufacturer's address and location of business activity

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