HEPAVAL®

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

Composition:

active substance: glutathione;

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

1 ampoule of solvent contains 4 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 tissues of the body. Its widespread presence is associated with a broad spectrum of biological functions and is fundamental for numerous biochemical and metabolic processes.

The sulfhydryl groups of cysteine, which are part of glutathione, act as powerful nucleophilic agents. Consequently, they become the primary target for electrophilic attack by chemical substances or their active metabolites, resulting in 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.

Furthermore, reduced glutathione (GSH), upon 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.

Due to 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, whereas in plasma it is rapidly broken down by gamma-glutamyltranspeptidase and gamma-glutamyl cyclotransferase. Thus, the plasma level of reduced glutathione (GSH), even after administration of high doses, remains low (peak plasma concentration is approximately 1 nmol/mL at 5 minutes after intravenous administration of 600 mg), while the level of the metabolite cysteine is higher (peak plasma concentration is approximately 17 nmol/mL). The blood concentration measured in whole blood reaches approximately 100 nmol/mL at 5–10 minutes after intravenous administration of 600 mg of 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 other similar substances.

Contraindications.

Hypersensitivity to the active substance or to other components of the medicinal 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 or women who are breastfeeding.

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

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

Method of Administration and Dosage.

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

In moderate degree of involvement: half of the above dose should be administered.

Preparation of the drug for administration.

For intramuscular administration, the drug should be completely dissolved directly in the vial using the solvent provided in the package.

For intravenous administration, the drug should be dissolved with the solvent from the package (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 solution.

Children. The possibility of use in children has not been studied.

Overdose.

No information regarding overdose is available.

Side effects.

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

Shelf life. 3 years.

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 the reach of children.

Packaging.

Powder for solution for injection 600 mg in vials №10, supplied with solvent (water for injection) 4 ml in ampoules №10, in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LABORATORIO ITALIANO BIOCHIMICO FARMACEUTICO LISAPHARMA S.P.A.

Manufacturer's address.

VIA LICINIO, 11 – 22036 ERBA (Province of Como), Italy.

Marketing Authorisation Holder.

LLC "VALARTIN PHARMA".

Address of the Marketing Authorisation Holder.

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