Libra®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT lIBRA® (libra®)

Composition:

Active substance: L-arginini hydrochloridum;

100 ml of solution contains arginine hydrochloride 4.2 g (1000 ml contains 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. Blood 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.

Arginine exhibits anti-hypoxic, membrane-stabilizing, cytoprotective, antioxidant, anti-radical, and detoxifying activities. It functions 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 effects due to its antioxidant, anti-hypoxic, and membrane-stabilizing activities and positively influences energy supply processes in hepatocytes.

Arginine serves as a substrate for NO-synthase—an enzyme that catalyzes the production of nitric oxide in endothelial cells. The drug activates guanylate cyclase and increases the level of cyclic guanosine monophosphate (cGMP) in vascular endothelium. It reduces activation and adhesion of leukocytes and platelets to the vascular endothelium, suppresses 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 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 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 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; 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 the medicinal product Libra, it should be considered 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 lead to increased blood potassium concentration. Concomitant use with aminophylline may increase 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 cause hyperkalemia.

The drug should be used with caution in patients with endocrine gland dysfunction. Arginine 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, 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 regarding the use of the drug during breastfeeding.

Ability to affect the speed of reactions 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; 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 dose is 5–10 ml per kg of body weight per day.

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 is indicated for use 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. Physiological responses should be monitored, and vital functions should be supported. 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, 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 blood pressure, changes in heart rhythm, chest pain.

Nervous system: headache, dizziness, feeling of fear, weakness, seizures, tremor—more frequent with infusion rates exceeding recommended.

Laboratory parameters: hyperkalemia.

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 status. Prescription only.

Manufacturer. Private Joint-Stock Company "Infuziya".

Manufacturer's address and location of business operations.

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