ParenteralAcute lymphoblastic leukaemiaAdult: As colaspase: 5,000 IU/m2 via IV infusion over 0.5-2 hr given every 3rd day. As crisantaspase: 6,000 IU/m2 (200 IU/kg) via IM, IV or SC inj 3 times wkly for 3 wk. Alternatively, when used as substitute, 25,000 IU/m2 for each planned colaspase dose, or 25,000 IU/m2 3 times wkly (Mon/Wed/Fri) for 6 doses for each planned pegaspargase dose, given via IM or IV inj. As pegaspargase: 2,500 IU/m2 via IM inj (Max 2 mL/inj site) or IV infusion over 1-2 hr, no more frequently than every 14 days.
Child: >1 yr As colaspase: Same as adult dose.
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As colaspase: Severe: Contraindicated.
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Colaspase (IV infusion): Dilute w/ NaCl 0.9% inj to a final volume of 50-250 mL. Crisantaspase (IM/IV/SC): Add 1 or 2 mL of preservative-free NaCl 0.9% inj to provide a soln containing 10,000 or 5,000 IU/mL, respectively, injected slowly against the inner wall of the vial, gently mixed and swirled. Do not shake or invert. Pegaspargase (IV infusion): Dilute in 100 mL NaCl or dextrose 5% inj.
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History of serious pancreatitis, hypersensitivity, serious thrombotic (e.g. sagittal sinus thrombosis, pulmonary embolism) and haemorrhagic events related to asparaginase therapy. Lactation. Severe hepatic impairment (as colaspase).
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Patient w/ mild pancreatitis, hyperglycaemia. Hepatic impairment.
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Hyperglycaemia, abnormal transaminase level, hyperbilirubinaemia, local reactions; nausea, vomiting, abdominal discomfort, diarrhoea; fever, rash, dyspnoea, bronchospasm, urticaria, hypotension, laryngeal oedema; altered blood lipids and cholesterol, hypoalbuminaemia, hyperammonaemia, uraemia, renal failure; drowsiness, depression, lethargy, confusion, dizziness, neurotoxicity, hallucination, seizure, Parkinson-like syndrome. Rarely, myalgia, reactive arthritis, transient bone-marrow depression, marked leucopenia.
Potentially Fatal: Serious hypersensitivity reactions (e.g. anaphylaxis), acute pancreatitis, hepatotoxicity, thrombosis, coagulopathy, ketoacidosis, hyperthermia.
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Monitor CBC w/ differential, amylase, lipase, insulin, triglycerides, blood glucose, and coagulation parameters. Perform LFT regularly. For colaspase, monitor trough serum asparaginase activity 3 days after admin.
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Increased risk of anaphylaxis and neurotoxicity w/ vincristine. May increase the risk of coagulation abnormality w/ corticosteroid (e.g. prednisone). May diminish the effect on malignant cells of methotrexate. May increase serum concentration of dexamethasone.
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Interferes w/ thyroid function tests by producing transient reduction of thyroxine-binding globulin concentration.
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Description:
Mechanism of Action: Asparaginase, an antineoplastic agent, reduces L-asparagine circulating levels by catalysing the deamidation of the amino acid to aspartic acid and ammonia. This results in inhibition of the cellular proliferation of leukemic cells, which lack asparagine synthetase and depend upon exogenous source of asparagine for survival. It is derived from E coli as colaspase (unconjugated) and as pegaspargase (conjugated w/ polyethylene glycol), or from Erwinia chrysanthemi as crisantaspase.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 1-2 hr (as crisantaspase).
Distribution: Distributed mainly w/in the intravascular space; approx 20% in the lymph.
Excretion: Via urine (in small amount). Elimination half-life: Colaspase: 14.2-44.2 hr. Crisantaspase: Approx 7.5 hr (IV); approx 16 hr (IM).
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Store between 2-8°C. Protect from light.
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L01XX02 - asparaginase ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
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Anon. Asparaginase (Erwinia). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/10/2016. Buckingham R (ed). Asparaginase. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/10/2016. Erwinaze Injection, Powder, Lyophilized, for Solution (Jazz Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/10/2016. Joint Formulary Committee. Crisantaspase. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/10/2016. McEvoy GK, Snow EK, Miller J et al (eds). Asparaginase (Erwinia chrysanthemi). AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 10/10/2016. McEvoy GK, Snow EK, Miller J et al (eds). Pegaspargase. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 11/10/2016. Oncaspar Injection, Solution (Baxalta US Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/10/2016.
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