Vero-asparaginase (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Veropharm, LLC (Russia)

ATC Code

L01XX02 (Asparaginase)

Active Substance

Asparaginase (USAN)

Dosage Form

Vero-Asparaginase

Lyophilizate for preparation of solution for intravenous and intramuscular administration 10,000 IU: fl. 1, 5, or 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for intravenous and intramuscular administration as a white porous mass.

* the L-asparaginase substance contains mannitol in an amount of 50 mg per 10,000 IU.

Excipients: glycine (aminoacetic acid) – 50 mg.

Glass bottles (1) – cardboard packs.
Glass bottles (5) – cardboard packs with dividers.
Glass bottles (10) – cardboard packs with dividers.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; other antineoplastic agents

Pharmacological Action

Antineoplastic agent. The mechanism of action of asparaginase appears to be associated with the hydrolysis of asparagine, which is necessary for the growth of tumor cells, leading to disruption of protein, DNA, and RNA synthesis and to cell death.

Pharmacokinetics

After intramuscular administration, C_max in plasma is reached after 14-24 hours. Protein binding is 30%. Penetrates the blood-brain barrier to a limited extent; the concentration in the cerebrospinal fluid is less than 1% of the plasma concentration.

It is metabolized by slow breakdown involving the reticuloendothelial system. Stimulates the formation of antibodies that affect plasma clearance.

The routes of elimination have not been definitively established. It appears in the urine only in trace amounts.

Indications

Acute lymphoblastic leukemia, lymphogranulomatosis, malignant non-Hodgkin’s lymphomas. The drug is also used as part of combination therapy for myeloblastic leukemia and chronic lymphocytic leukemia.

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific disease, its stage, and the chosen anticancer therapy protocol.

Administer the drug intravenously or intramuscularly after reconstitution.

Reconstitute the 10,000 IU lyophilisate with 1-2 mL of Water for Injections or 0.9% Sodium Chloride solution.

Gently swirl the vial until a clear solution is obtained; do not shake vigorously.

Use the prepared solution immediately; do not store reconstituted product.

For intravenous administration, infuse the solution over not less than 30 minutes into a running infusion of 0.9% Sodium Chloride or 5% Dextrose solution.

For intramuscular administration, inject no more than 2 mL into a large muscle mass.

Monitor patients closely for hypersensitivity reactions, especially during the initial administration; have resuscitation equipment available.

Perform baseline and periodic monitoring of complete blood count, liver and pancreatic function, coagulation parameters, blood glucose, and uric acid levels throughout therapy.

Adjust or discontinue therapy based on the severity of adverse reactions, particularly pancreatitis, hepatic toxicity, or severe hypersensitivity.

Adverse Reactions

From the digestive system: pancreatitis (accompanied by severe pain with nausea and vomiting), impaired liver function (possible development of fatty liver), loss of appetite.

From the blood coagulation system: possible asymptomatic decrease in the level of fibrinogen and factors V and VIII, less often – factors VII and IX; rarely – bleeding or hemorrhage.

From the central nervous system: headache, fatigue, drowsiness, confusion, nervousness, unusual tiredness, depression, hallucinations.

From metabolism: hyperglycemia, hyperuricemia, azotemia (not associated with impaired renal function), hypoalbuminemia.

Allergic reactions: difficulty breathing, arthralgia, skin rash, itching; rarely – anaphylactic shock (in children with advanced stages of leukemia).

Other: nephropathy (associated with hyperuricemia), leukopenia, hyperthermia, immunosuppression.

Contraindications

Pancreatitis (including history), hepatic insufficiency, renal insufficiency, pregnancy, lactation period, hypersensitivity to asparaginase.

Use in Pregnancy and Lactation

Asparaginase is contraindicated during pregnancy and lactation.

Women of childbearing potential should use reliable methods of contraception during therapy.

Experimental studies have established the teratogenic and mutagenic effects of asparaginase.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in renal insufficiency.

Pediatric Use

Used in children according to indications.

Geriatric Use

Use with caution in elderly patients with impaired liver and/or kidney function.

Special Precautions

Use with caution in patients with chickenpox (including recently contracted or after contact with sick individuals), with herpes zoster (the risk of developing a systemic disease with a fatal outcome increases), acute infectious diseases, diabetes mellitus, gout or nephrolithiasis (including history), impaired liver function.

Caution should be exercised when using in patients who have previously received cytotoxic drugs or radiation therapy.

During treatment, systematic monitoring of peripheral blood counts, liver, kidney, and pancreatic function, blood coagulation parameters, plasma glucose and uric acid concentrations, as well as the state of the hematopoietic system (bone marrow aspirate) is necessary. Due to the toxic effect of asparaginase on the central nervous system, regular examinations by specialists are recommended.

Vaccination of patients and their family members should not be carried out.

Experimental studies have established the carcinogenic effect of asparaginase.

Drug Interactions

With simultaneous use with vincristine, prednisone, an increase in the hyperglycemic, myelotoxic, and neurotoxic effects of asparaginase is possible.

With simultaneous use with cytotoxic drugs, mutual enhancement of their effects is possible.

With simultaneous use with methotrexate, a weakening of the effect of methotrexate is possible due to inhibition of cell replication.

Impairs the detoxification of drugs in the liver.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.