L-Asparaginase injection is used as part of combination chemotherapy regimens for the treatment of patients with acute lymphoblastic leukemia (ALL).

L-Asparginase works by reducing the level of asparagine in the blood. Certain leukemic cells cannot produce asparagine on their own and depend on external sources. By depleting asparagine, L-Asparginase inhibits the growth of these cancer cells and leads to their death. Normal cells are less affected because they can produce asparagine themselves.

L-Asparginase contains the enzyme L-asparagine amidohydrolase (EC-2). It is not absorbed through the gastrointestinal tract, so it must be administered by intramuscular (IM) or intravenous (IV) injection. The IM route is effective and does not increase immunogenicity. When given IM, no more than 2 ml should be injected at one site. The activity of L-Asparginase is measured in International Units (IU). One IU is defined as the amount of enzyme required to produce 1 micromole of ammonia per minute at pH 7.3 and 37°C. The product is available as a sterile white lyophilized powder, with each vial containing 5,000 IU or 10,000 IU.

This drug may have toxic properties and must be handled and administered with care. Special handling procedures should be reviewed prior to handling and followed diligently during reconstitution and administration. Inhalation of dust or aerosols and contact with skin or mucous membranes, especially those of the eyes, must be avoided.

As a component of selected multiple-agent induction regimens, L-Asparaginase may be administered by either the intravenous or the intramuscular route. When administered intravenously this enzyme should be given over a period of not less than thirty minutes through the side arm of an already running infusion of sodium chloride injection or dextrose injection 5%. L-Asparaginase has little tendency to cause phlebitis when given intravenously. Anaphylactic reactions require the immediate use of epinephrine, oxygen and intravenous steroids. When administering L-Asparaginase intramuscularly, the volume at a single injection site should be limited to 2ml. If a volume greater than 2ml is to be administered, two injection sites should be used. Unfavorable interactions of L-Asparaginase with some antitumor agents have been demonstrated. It is recommended, therefore, that L-Asparaginase be used in combination regimens only by physicians familiar with the benefits and risks of a given regimen. During the period of its inhibition of protein synthesis and cell replication, L-Asparaginase may interfere with the enzymatic detoxification of other drugs, particularly in the liver.

Geriatric Use: Clinical studies of L-Asparaginase did not include sufficient numbers of subjects aged 65 and older

to determine whether they respond differently from younger subjects.

L-Asparaginase may reduce or completely eliminate the effect of Methotrexate on malignant cells. Concurrent or immediate prior intravenous use of L-Asparaginase with Vincristine and Prednisolone may increase toxicity.

Drug/Laboratory Test Interaction: L-Asparaginase can interfere with thyroid function test results by causing a rapid and significant decrease in serum thyroxine-binding globulin levels within two days after the first dose. These levels usually return to baseline within four weeks after the final dose of L-Asparaginase.

The following serious adverse reactions are associated with L-Asparaginase therapy:

• Anaphylaxis and severe allergic reactions
• Severe thrombosis
• Pancreatitis
• Glucose intolerance
• Coagulation disorders
• Hepatotoxicity and abnormal liver function

The most common adverse effects include allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, CNS thrombosis, coagulation abnormalities, hyperbilirubinemia, and elevated liver enzymes.

Pregnancy Category C. Animal studies in mice and rats have shown that L-Asparaginase may reduce weight gain in mothers and fetuses when administered at doses greater than 1000 IU/kg (approximately equivalent to the recommended human dose adjusted for body surface area). Findings included fetal resorption, gross abnormalities, and skeletal defects. In rabbits, intravenous doses of 50 or 100 IU/kg (approximately 10–20% of the human dose) during gestation days 8 and 9 caused dose-related embryotoxicity and malformations. There are no adequate, well-controlled studies in pregnant women. L-Asparaginase should be used during pregnancy only if clearly necessary.

Nursing Mothers: It is not known whether L-Asparaginase is excreted in human milk. Since many drugs are excreted in breast milk and may cause serious adverse effects in infants, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of treatment to the mother.

L-Asparaginase for injection is supplied in flint glass vials containing 5,000 IU or 10,000 IU as a sterile, lyophilized powder for reconstitution prior to use.

Cytotoxic Chemotherapy

Store vials in a refrigerator at 2–8°C. Protect from light. Do not freeze. This product does not contain preservatives. Reconstituted solution should be stored at 2–8°C and used within 8 hours or discarded earlier if it becomes cloudy.