L-Asparaginase

Indications

L-Asparaginase is used for: Acute Lymphocytic Leukemia

Adult Dose

Parenteral Induction of remissions in acute lymphoblastic leukaemia Adult: 1000 units/kg/day via IV inj for 10 days after treatment with vincristine and prednisone or prednisolone. Alternatively, 6000 units/m2 via IM inj, given every 3rd day for 9 doses during treatment with vincristine and prednisone or prednisolone. As monotherapy: 200 units/kg/day via IV inj for 28 days.

Child Dose

Parenteral Induction of remissions in acute lymphoblastic leukaemia Child: As monotherapy: 200 units/kg/day via IV inj for 28 days, to be given over at least 30 min in a running infusion of normal saline or glucose 5%.

Renal Dose

Administration

IV inj to be given over at least 30 min in a running infusion of normal saline or glucose 5%. For IM admin, no more than 2 ml of a solution in normal saline should be injected at a single site.

Contra Indications

Hypersensitivity. History of pancreatitis, thrombosis, or serious pancreatitis events with prior L-asparaginase treatment.

Precautions

Should be used after skin testing, in hospital setting. Liver disease, frequently blood count monitoring. Lactation. Lactation: It is not known whether this drug is excreted in milk. Because of the potential for serious adverse reactions in nursing infants from Elspar, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy-Lactation

Interactions

Activity of methotrexate may be reduced if L-asparaginase is given before hand. Potentially Fatal: IV admin of asparaginase may increase vincristine neurotoxicity.

Adverse Effects

Side effects of L-Asparaginase : >10% Abdominal cramps (70%),Anorexia (70%),Azotemia (66%),Nausea (50-60%),Vomiting (50-60%),Agitation (10-60%),Depression (10-60%),Fatigue (10-60%),Fever (10-60%),Chills (10-60%),Anaphylaxis (15-35%),Coma (25%),Confusion (25%),Somnolence (25%),Stupor (25%),Pancreatitis, acute (15%) 1-10% Hyperglycemia,Stomatitis,Hyperuricemia <1% Disorientation,Drowsiness,Hallucination,Headache,Hyperthermia,Parkinsonian symptoms,Venous thrombosis,Hypotension,Intracranial hemorrhage,Cerebrovascular hemorrhage,Peripheral edema,Thrombosis,Cough,Hypofibrinogenemia,Depression of clotting factors,Severe protein C deficiency,Decrease antithrombin III,Glucosuria,Hemorrhagic pancreatitis,Ketoacidosis,Hepatotoxicity,Urticaria,Weight loss,Acute renal failure

Mechanism of Action

Asparaginase interferes with malignant cell growth by breaking down asparagine to aspartic acid and ammonia as leukemic cells are unable to synthesise asparagine and depends on exogenous source of asparagine for survival. It acts on the G1 phase of the cell cycle.