HEPAVAL®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ГЕПАВАЛ® HEPAVAL®

Composition:

Active substance: glutathione;

1 vial contains 643 mg of sodium glutathione, equivalent to 600 mg of glutathione;

1 ampoule of solvent contains 5 ml of water for injections.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white hygroscopic powder; clear, colorless, odorless liquid.

Pharmacotherapeutic group. Antidotes. ATC code V03A B32.

Pharmacological Properties

Pharmacodynamics

Glutathione is a tripeptide that is a natural component of cells in all body tissues. Its widespread presence is associated with a broad spectrum of biological functions and is fundamental to numerous biochemical and metabolic processes.

The sulfhydryl groups of cysteine contained in glutathione act as powerful nucleophilic agents. Consequently, they become the primary target for electrophilic attack by chemical substances or their active metabolites, leading to the inactivation of potentially toxic exogenous compounds. Thus, the drug exerts a protective effect on vital nucleophilic sites, the attack on which initiates the process of cellular damage.

In addition, glutathione (GSH), upon reduction following interaction with a large number of oxidized organic metabolites, forms less toxic conjugated compounds, which are subsequently more easily metabolized and excreted as mercapturic acids.

Given these properties, glutathione is indicated in cases of hepatotoxic reactions, the development mechanisms of which may include ethyl or drug-induced hepatotoxicity, or pathogenetically determined hepatotoxicity associated with impaired detoxification mechanisms.

Pharmacokinetics

After intravenous administration, glutathione is predominantly distributed into erythrocytes, while in blood plasma it is rapidly degraded by gamma-glutamyltransferase and gamma-glutamyl-cyclotransferase. As a result, the plasma level of reduced glutathione (GSH) remains low even after high doses (peak plasma concentration—approximately 1 nmol/mL at 5 minutes after intravenous administration of 600 mg), whereas metabolite cysteine levels are higher (peak plasma concentration—approximately 17 nmol/mL). The blood concentration measured in whole blood reaches approximately 100 nmol/mL within 5–10 minutes after intravenous administration of 600 mg glutathione. The drug concentration in blood gradually decreases, nearly returning to baseline levels approximately 60 minutes after administration.

Clinical characteristics.

Indications.

Prevention of neuropathy induced by chemotherapy with cisplatin or similar agents.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the product.

Interaction with other medicinal products and other forms of interaction.

Unknown.

Special precautions for use.

Use during pregnancy or breastfeeding.

Although glutathione showed no signs of embryotoxic or fetotoxic effects in experimental studies, its use is not recommended in pregnant women and women who are breastfeeding.

Ability to influence the reaction rate when driving or operating machinery.

Glutathione does not affect the ability to drive or operate machinery.

Dosage and Administration.

In the most severe degree of injury: 600–1200 mg (1–2 vials) daily by intramuscular or slow intravenous injection.

In moderate degree of injury: half the above-mentioned dose should be administered.

Preparation of the drug for administration.

For intramuscular administration, the drug must be completely dissolved directly in the vial using 4 mL of solvent from the 5 mL ampoule supplied in the kit. The remaining solvent in the ampoule should not be used or stored.

For intravenous administration, the drug must be dissolved with the solvent provided in the kit (water for injections) and administered either by direct slow injection or by infusion after adding the prepared solution to at least 20 mL of sterile infusion fluid.

Children. The use of the drug in children has not been studied.

Overdose.

There is no information available regarding overdose.

Adverse Reactions.

In rare cases, nausea, vomiting, headache, and skin rashes may occur. These reactions usually disappear after discontinuation of therapy.

Shelf life. 3 years from the date of manufacture of the drug in bulk form.

Storage conditions.

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

The reconstituted solution is stable for approximately 2 hours when stored at room temperature and for at least 8 hours when stored at 0 to +5 °C.

Keep out of reach of children.

Packaging.

Powder for solution for injection 600 mg in vials, 10 vials per pack, together with solvent (water for injections), 5 ml in ampoules, 10 ampoules per pack, in a cardboard box.

Prescription status.

By prescription only.

Manufacturer.

LLC "Valartin Pharma" (manufacturing from bulk form by the manufacturer LABORATORIO ITALIANO BIOCHIMICO FARMACEUTICO LISAPHARMA S.P.A., Italy).

Manufacturer's address and place of business.

Chayky, 60 Grushevskoho St., Kyiv-Sviatoshyn district, Kyiv region, 08135, Ukraine.