Parenteral Manual

Asparaginases (Erwinia, Pegaspargase, Recombinant Crisantaspase)

Disclaimer: Official controlled document is the CHEO online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
Original Date: 
August 2005
Revised Date: 
February 2021
  • Component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia 
  • Acute myeloid leukemia (off label)  
Reconstitution and Stability: 

Refrigerate. Do NOT freeze


  • Available as a clear solution in a 5 mL vial containing 750 units/mL
  • Single use vial. Preservative free.
  • Dilute in 100 mL of 0.9% NaCl.  Diluted solution should be stored refrigerated (2 - 8 degrees celcius).  Storage of diluted solution should not exceed 48 hours from time of preparation to completion of administration


  • Reconstitute vial with 1 mL 0.9% NaCl to give a 10 000 unit/mL concentration. Preservative free.
  • Caution: vigorous shaking may result in loss of potency. To mix, direct 0.9% NaCl to the side of the vial, then gently rotate the vial.
  • Withdraw from vial within 15 minutes of reconstitution.  Filter needle must be used.
  • Stable in syringe or a minibag at room temperature for 4 hours
  • Do not refrigerate syringe

Recombinant Crisantaspase Pseudomonas Fluorescens (RC-P)

  • Available as a clear to opalescent, slightly yellow solution in a 0.5 mL single use vial containing 10 mg of recombinant crisantaspase
  • Store unopened vials in the fridge, in its supplied carton. Protect vials from light. Let vials sit at room temperature for 5-10 minutes prior to dose preparation
  • Do NOT shake. Gently swirl vials.
  • For IV administration: Dilute in 100 mL of 0.9% NaCl (Latex free, PVC free, DEHP free bag).  Final product stable 4 hours at room temperature and does not need to be protected from light. Initiation of the fully diluted recombinant crisantaspase must be started within 2 hours of preparation. Administration should be completed within 4 hours of preparation.
  • For AALL1931: Only ONE lot number should be used for each dose. More than one lot number can be used for each course.

- Solutions Compatible:

  • Pegaspargase: D5W, 0.9% NaCl
  • Erwinia-L-asparaginase: 0.9% NaCl
  • Recombinant Crisantaspase (RC-P): 0.9% NaCl

- DO NOT mix with other drugs


(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)


Erwinia-L-asparaginase: YES, inject into a large muscle
***Maximum 2 mL per injection site***

Recombinant Crisantaspase (RC-P): YES, inject into a large muscle
***Maximum 2 mL per injection site***


IV Direct

ERWINIA-L-asparaginase: YES

IV Intermittent Infusion

Pegaspargase : YES, in 100 mL of 0.9% NaCl or D5W over 1-2 hours
Erwinia-L-asparaginase: YES, in 100 mL 0.9% NaCl over 1 hour

Recombinant Crisantapase (RC-P): YES, in 100mL 0.9NaCl over 2 hours.  Non-PVC bags and DEPH-free tubing must be used

IV Continuous Infusion NO

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

Pegaspargase (ONCASPAR):

  • 2500 units/m2/dose as part of a comboination chemotherapy regimen; do not administer more frequently than every 14 days


  • 25 000 units/m2  , 3 times per week x 6 doses to replace each dose of pegaspargase
  • Dosage may differ according to protocol

Recombinant Crisantaspase (RC-P):
Expected Investigational starting dosing: 

  • 25 mg/m2 IM 3 times per week x 6 doses to replace each dose of Pegaspargase


  • 37.5 mg/m2 IV 3 times per week x 6 doses to replace each dose of Pegaspargase
  • Refer to protocol for patient specific cohort dosing 
Potential hazards of parenteral administration: 

Immediate (within a few minutes to hours)

  • Anaphylaxis, other allergic reactions (6-43%) - urticaria, pruritus, respiratory distress, hypotension, chills, fever)
  • Nausea and vomiting rare - more common with initial doses
  • Pain/bruising at injection site (IM administration) - hold site at least 5 minutes after injection or until bleeding stops.  Apply ice if platelet counts low.

Delayed (within a few days to weeks)

  • Hemorrhagic and thrombotic cardiovascular events - decreased fibrinogen, clotting factors, antithrombin
  • Hepatotoxicity - hypoalbuminemia, increased transaminases
  • Hyperglycemia - monitor urine/blood glucose; hypoglycemia possible
  • Pancreatitis - elevated serum amylase, assess for abdominal tenderness
  • Myelosuppression
  • Have anaphylaxis kit at bedside. Out-patients should remain in the clinic for at least one hour following injection. NOTE: anaphylaxis may be delayed following IM injection.
  • Insulin may be required for severe hyperglycemia.
  • Pegaspargase is contraindicated with a history of severe pancreatitis with any prior asparaginase therapy, serious thrombosis with any prior asparaginase therapy, or serious hemorrhagic events with any prior asparaginase therapy.
  • Pegaspargase may affect coagulation factors and predispose to bleeding and/or thrombosis. Caution should be used when administering any concurrent anticoagulant therapy

Drug/Disease Interactions

  • Give asparaginase AFTER methotrexate, cytarabine and vincristine NOT BEFORE 
  1. Erwinase Product Monograph (EUSA/Jazz Canada)
  2. Erwinase Product Monograph (Jazz-USA)
  3. COG Memo January 2, 2015 - Approval of IV route of Erwinia asparaginase
  4. Recombinant Crisantaspase Pseudomonas Fluorescens (RC-P) Pharmacy Manual (Jazz-USA) version 6.0 Version Date 10 Nov 2020 
  5. Oncaspar – Pegaspargase Product Monograph. Servier Canada. Version 21 Jan 2021. 
  6. Erwinia and Pegaspargase. Children’s Oncology Group. Parenteral and oral Chemotherapy Administration Guidelines used by the Children’s Oncology Group. Version 10.1 Version Date: 05/01/2020
  7. Erwinase Product Monograph (Jazz Pharmaceuticals France). Version 30 Aug 2016 (access 23 Feb2021 via HC product database website) 
  8. Investigator’s Brochure for Recombinant Crisantaspase produced in Pseudomonas fluorescens. Version 3.0. Version date 20 Jan 2021 

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