Asparaginase

DRUG NAME:

(a) Asparaginase
(b) Erwinia asparaginase
(c) Pegaspargase

SYNONYMS:

(a) A-ase,1 ASN-ase, Colaspase, Crasnitin,2 Elspar,3 L-asparagine

1
amidohydrolase
(b) Crisantaspasum,2 Krisantaspaasi, Krisantaspas
(c) PEG-L-asparaginase,2 Pegaspargasa, Pegaspargasum

COMMON TRADE NAMES:

(a) KIDROLASE
(b) ERWINASE
(c) ONCASPAR

CLASSIFICATION: antitumour antibiotic

Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

MECHANISM OF ACTION:
Asparaginase hydrolyzes the amino acid L-asparagine to L-aspartic acid and ammonia.1,4 Asparagine is required for
DNA synthesis and cell survival; however, most cells are capable of synthesizing asparagine from glutamine. Acute
lymphoblastic leukemia (ALL) cells lack adequate levels of the required enzyme, asparagine synthetase, and cannot
5
survive asparagine depletion. Asparaginase is cycle-specific for the G1 phase.
There are three formulations of asparaginase available. These will be identified in the text as:
Asparaginase (L-asparaginase isolated from E.coli )
Erwinia asparaginase (L-asparaginase isolated from Erwinia chrysanthemi, previously called Erwinia carotova6)7
Pegaspargase (L-asparaginase isolated from E.coli and attached to polyethylene glycol)
Erwinia asparaginase is serologically and biochemically distinct from asparaginase, although the antineoplastic
activity and toxicity is similar. Pegaspargase has a longer half-life and decreased toxicity.

PHARMACOKINETICS:
Oral Absorption
Distribution

Metabolism

Excretion

denaturation and peptidase digestion within GI tract1,8

diffuses poorly from the capillaries; approximately 80% of the dose remains within the
intravascular space1; IM injection yields a much larger volume of distribution
cross blood brain barrier?
not detectable in cerebrospinal fluid (CSF), but CSF
asparagine is depleted with systemic administration of
any formulation9
volume of distribution
asparaginase9: 3 L/m2
Erwinia asparaginase9: 5 L/m2
pegaspargase9: 2 L/m2
plasma protein binding
no information found
10
unknown
active metabolite(s)
no information found
inactive metabolite(s)
no information found
unknown, possibly using reticuloendothelial system10
urine
asparaginase,5 pegaspargase11: trace amounts
feces
no information found

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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Asparaginase

Asparaginase

asparaginase IM12: 26-60 h

Erwinia asparaginase IM12: 16 h

terminal half life

pegaspargase IM12: 5.5-7 d

asparaginase9: 1.4 mL/min/m2
Erwinia asparaginase9: 3.4 mL/min/m2
pegaspargase9: 0.15 mL/min/m2

clearance

USES:
Primary uses:
abc
*Leukemia, acute lymphoblastic
*Leukemia, acute lymphoblastic and hypersensitivity to
bc
asparaginase
*Leukemia, acute myeloid a
a
*Leukemia, chronic lymphocytic
a
*Lymphoma, Hodgkins
13 a
Lymphoma, non-Hodgkins

Other uses:

*Health Canada approved indication

a

asparaginase
Erwinia asparaginase
c
pegaspargase
b

SPECIAL PRECAUTIONS:
Contraindications:
Asparaginase is contraindicated in patients with a history of an allergy to asparaginase, or past or present
pancreatitis.5
Erwinia asparaginase is contraindicated in patients with a history of allergy to Erwinia asparaginase, or past or
present pancreatitis.14
Pegaspargase is contraindicated in patients with a history of allergy to pegaspargase, or past or present
pancreatitis, or in patients who have experienced significant hemorrhagic or thrombotic side effects previously with
other formulations of asparaginase.15
Cautions:
Significant hypersensitivity reactions may occur with all three formulations. During administration, resuscitation
equipment and emergency drugs should be readily available.15,16 Reactions include rash, urticaria, edema,
1
hypotension, respiratory distress, chills, fever and anaphylaxis, which may result in sudden death. An intradermal
1,14,17
test dose is recommended for asparaginase but not for Erwinia asparaginase or pegaspargase.
Asparaginase has the highest frequency at 15-35%.5 Although skin testing is not completely reliable in predicting
asparaginase hypersensitivity, an intradermal test dose is generally recommended prior to the first dose, or before
restarting therapy after several days.1 While a positive skin test is often considered a contraindication to
asparaginase treatment, some clinicians choose to use a desensitization procedure in positive reactors or before
restarting therapy after several days. Anaphylactic reactions can occur within one-half to one hour following the
first injection, including during skin testing, but occur mainly between the fifth and ninth injection.16 Risk factors
include IV administration (decreased in IM or SC administration), prolonged therapy, high dose (> 6,000-12,000
units/m2), previous asparaginase therapy, and intermittent dosing.16
Erwinia asparaginase may be used in patients who had an allergic reaction to asparaginase (see dosing
guidelines).7 Up to 33% of patients who had an allergic reaction to asparaginase will also react to Erwinia
7
asparaginase.

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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Asparaginase

Pegaspargase is the least immunogenic, and may be used in patients who had an allergic reaction to
asparaginase or Erwinia asparaginase (see dosing guidelines).16 Treatment-limiting reactions occurred in 9% of all
patients, 14% of patients who had an allergic reaction to asparaginase, and 26% of patients who had an allergic
reaction to both asparaginase and Erwinia asparaginase.18
Administration: Toxicity, other than hypersensitivity reactions, may be more severe when the drug is administered
1
daily rather than weekly. For pegaspargase, IM administration is preferred over IV administration due to a lower

incidence of hepatotoxicity, coagulopathy, gastrointestinal, and renal disorders.11

Carcinogenicity: No information found.
Mutagenicity: Not mutagenic in Ames test.15 Not known if asparaginase, Erwinia asparaginase or pegaspargase
are clastogenic.
Fertility: No information found.
19
Pregnancy: FDA Pregnancy Category C. Animal studies have shown fetal risks and there are no controlled
studies in women. Asparaginase, Erwinia asparaginase and pegaspargase should be given only if potential benefit
justifies the potential risk to the fetus.

Breastfeeding is not recommended due to the potential secretion into breast milk.5
Special populations: Adults experience a higher incidence of toxicities, other than hypersensitivity reactions,
5
compared to children. Patients can form asparaginase antibodies, which at least partially explains the high
interpatient variability in asparaginase pharmacokinetics.10 Clinically, the formation of these antibodies may result in
hypersensitivity reactions or may lead to a faster decrease in asparaginase activity.

SIDE EFFECTS:
The table includes adverse events that presented during drug treatment but may not necessarily have a causal
relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event
rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they
were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be
clinically important.20 When placebo-controlled trials are available, adverse events are included if the incidence is >
5% higher in the treatment group.
The table refers to asparaginase unless otherwise noted. Generally, the toxicities seen with Erwinia
asparaginase are very similar to asparaginase.21 Pegaspargase toxicities have a later onset than comparable
11
toxicities of asparaginase.

ORGAN SITE

SIDE EFFECT
Clinically important side effects are in bold, italics

allergy/immunology

hypersensitivity reactions (anaphylaxis 15-35%,5 pegaspargase 1-5%11)

blood/bone marrow/
febrile neutropenia

anemia (<1%, nadir 14 days, recovery 21 days,5 pegaspargase (1-5%) nadir 14 days,
recovery 21 days11)
leucopenia (<1%, nadir 14 days, recovery 21 days,5 pegaspargase (1-5%) nadir 14
11
days, recovery 21 days )
thrombocytopenia (<1%, nadir 14 days, recovery 21 days,5 pegaspargase (1-5%) nadir
14 days, recovery 21 days11)
11
tachycardia (pegaspargase: 1-5%)

cardiovascular
(arrhythmia)
coagulation

antithrombin III decreased (may be dose-limiting or fatal >10%)5

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

Page 3 of 9

Asparaginase

Asparaginase

ORGAN SITE

SIDE EFFECT
Clinically important side effects are in bold, italics

clotting factors V, VII, VIII, IX decreased (>10%)5

coagulation abnormalities (30%,21 Erwinia asparaginase 12%,18 pegaspargase 15%11)
fibrinogen decreased (>10%,5 pegaspargase 1-5%11)20
protein C severe decrease (>10%)5
thromboplastin increased (pegaspargase 1-5%)11
constitutional symptoms

fatigue (>10%,5 pegaspargase >5%11)

night sweats (pegaspargase 1-5%)11
16

weight loss (0.1-1%)

dermatology/skin

extravasation hazard: nonvesicant22

11

injection site reaction, pain, itching, erythema, inflammation (pegaspargase 1-5%)

gastrointestinal

emetogenic potential: rare,23 pegaspargase rare11,18,23

abdominal cramps (70%,5 pegaspargase 1-5%11)
anorexia (>10%,5 pegaspargase 1-5%11)
diarrhea (0.1-1%,16 pegaspargase 1-5%11)
stomatitis (1-10%)5
vomiting (<10%,23 pegaspargase > 5%11,18)

hepatic

hepatotoxicity (>0.01% and <0.1%,16 pegaspargase 1-5%11)

hepatobiliary/pancreas

pancreatitis acute (15%,5 pegaspargase >2%15)

infection

upper respiratory infection (pegaspargase 1-5%)18

sepsis5

metabolic/laboratory

albumin decrease possibly with peripheral edema (<1%,1,5} pegaspargase18)

alkaline phosphatase, transient increase (>10%,5 pegaspargase 1-5%11)
azotemia (>10%)5
bilirubin, transient increase (>10%,5 pegaspargase 1-5%11)
hyperglycemia requiring insulin (1.4%,21 pegaspargase 3%11)
hyperuricemia (1-10%,5 pegaspargase 1-5%11)
hypocholesterolemia (<1%)16
hypoglycemia (pegaspargase 1-5%)11
hypoproteinemia (pegaspargase 1-5%)11
5
11
transaminase, transient increase (>10%, pegaspargase 1-5% )

musculoskeletal

arthralgia, myalgia (pegaspargase 1-5%)11

neurology

coma (>25%)5
convulsions (10-60%,5 pegaspargase seizure (1-5%11)
neurotoxicity (>10%,5 pegaspargase 1-5%11); generally reversible
11

paresthesia (pegaspargase 1-5%)

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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Asparaginase

Asparaginase

ORGAN SITE

SIDE EFFECT
Clinically important side effects are in bold, italics

pain

headache (pegaspargase 1-5%)11

pulmonary

cough (>1%,5 pegaspargase 1-5%18)

respiratory distress (>0.1% and <1%,16 pegaspargase 1-5%11)

renal/genitourinary

hematuria (pegaspargase 1-5%)18

renal dysfunction (pegaspargase 1-5%)18
renal failure, acute (<1%,5 pegaspargase18)
urinary frequency (pegaspargase 1-5%)

18

thrombosis (<1%),11,18 pegaspargase (4%)11

vascular

Hypersensitivity reactions: see Special Precautions.

Coagulation abnormalities: Asparaginase may cause hemorrhagic and/or thrombotic events.24 These may occur
after several weeks of therapy or after completion of therapy, and may be dose-related. Bleeding may be caused by
a reduction in vitamin K-dependent clotting factors, a fall in fibrinogen levels, or decreased platelet aggregation to
25
collagen. Venous thrombosis may be caused by decreased antithrombin III, proteins C and S, and increased
thrombin.25 The majority of thromboses occur in the CNS.26 Hemostatic function should be monitored periodically
1
during therapy. If coagulation abnormalities occur, the risk of recurrence with further asparaginase therapy is very
low.24 Patients who require further asparaginase treatment may be treated prophylactically with fresh frozen plasma
plus low dose heparin, or low dose heparin 3 to 4 days after therapy, or fresh frozen plasma plus antithrombin III
concentrate.
Pancreatic effects: Impairment of pancreatic function occurs frequently and may be caused by decreased insulin
1
synthesis or necrosis and inflammation of the cells of the pancreas. Pancreatitis can occur despite normal serum
amylase, and can be fatal. Pancreatic function, including blood glucose, should be determined prior to and regularly
monitored during therapy.1
Hyperuricemia may result from cell lysis by cytotoxic chemotherapy and may lead to electrolyte disturbances or
acute renal failure.25 It is most likely with highly proliferative tumours of massive burden, such as leukemias, highgrade lymphomas and myeloproliferative diseases. The risk may be increased in patients with preexisting renal
dysfunction, especially ureteral obstruction. Follow the local institutional treatment guidelines for hyperuricemia and
20
tumour lysis syndrome.

INTERACTIONS:

AGENT
9

cytarabine

EFFECT

MECHANISM

MANAGEMENT

decreased effect of
cytarabine when
asparaginase is given
immediately prior to or with
cytarabine; enhanced
effect of cytarabine when
asparaginase is given after
cytarabine

suppression of asparagine
concentrations

refer to protocol by which

patient is being treated20

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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Asparaginase

Asparaginase

AGENT
1

methotrexate

serum thyroxine-binding
globulin1
vincristine1

EFFECT

MECHANISM

MANAGEMENT

decreased effect of
methotrexate when
asparaginase is given
immediately prior to or with
methotrexate; enhanced
effect of methotrexate
when asparaginase is
given after methotrexate
decreased total serum
thyroxine concentration

suppression of asparagine
concentrations

refer to protocol by which

patient is being treated20

decreased synthesis of
thyroxine-binding globulin
in liver
unknown

delay measurement until 4

weeks after asparaginase
therapy
refer to protocol by which
patient is being treated20

increased vincristine
neurotoxicity

SOLUTION PREPARATION AND COMPATIBILITY:

For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
Additional information: Potential overfill in KIDROLASE vials has been a cause of concern when calculating final
concentration. The manufacturer states that, when reconstituted with 4 mL SWI, the final concentration is 2,500
IU/mL 250 IU/mL.27 The BC Cancer Agency considers the final concentration to be 2,500 IU/mL. For IM injection,
28,29
or 1 mL to give
asparaginase may be reconstituted with 2 mL NS to give a final concentration of 5,000 IU/mL,
29
10,000 u/mL. For high-dose therapy, the practice of reconstituting the 10,000 IU vial with 0.5 mL or 1 mL of NS has
been used, but this is not supported by the literature and not recommended by the manufacturer.30

PARENTERAL ADMINISTRATION:
The table refers to asparaginase unless otherwise noted.
BCCA administration guideline noted in bold, italics
Intradermal28
Subcutaneous
Intramuscular (asparaginase, Erwinia asparaginase and
pegaspargase)

Direct intravenous

Intermittent infusion

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

*test dose only

has been used, not generally recommended
7
Erwinia asparaginase : can be used
commonly used: it is recommended that dose volumes
greater than 2 mL be administered in two sites if
possible to reduce pain of injection, although a single
site can be used if necessary.31-33
Erwinia asparaginase: maximum volume of 2 mL to be
injected at a single site; two injection sites should be
used for volumes greater than 2 mL.34
pegaspargase: maximum volume of 2 mL to be injected
at a single site; multiple injection sites should be used for
volumes greater than 2 mL.35
into the tubing of a running infusion of preservative-free
15,28
D5W or NS over > 30 minutes
7
Erwinia asparaginase : can be used
pegaspargase: not given direct IV11
over > 30 minutes28
Erwinia asparaginase7: can be used
pegaspargase: over 1-2 h15

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Asparaginase

BCCA administration guideline noted in bold, italics

Continuous infusion
Intraperitoneal
Intrapleural
Intrathecal
Intra-arterial
Intravesical

no information found
no information found
no information found
has been used36
no information found
no information found

*MD or RN to administer test dose as per institutional policy.

DOSAGE GUIDELINES:
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease,
response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count
(ANC) and liver function.20 Dosage may be reduced, delayed or discontinued in patients with bone marrow
depression due to cytotoxic/radiation therapy or with other toxicities.
Adults:
BCCA usual dose noted in bold, italics
Intravenous/intramuscular
asparaginase:

Cycle Length:
n/a37:

test dose: 2 units intradermally and observe for 1 h

then: 10,000 units IV daily on days 17-28 inclusive
(total dose 120,000 units)

n/a13:

test dose: 2 units intradermally and observe for 1 h

then: 10,000 units/m2 IV daily on days 15, 17, 19, 22, 25, 28
2
(total dose 60,000 units/m )

n/a33:

200-1,000 units/kg/day IV or IM daily on days 1-28 inclusive

(total dose is 5,600-28,000 units/kg)
may be continued for an additional 14 days if complete
remission is not obtained
(in this case: total dose 8,400-42,000 units/kg)

n/a33:

400 units/kg IV or IM daily Monday and Wednesday, 600

units/kg daily on Friday for 4 weeks
(total dose 4,800 units/kg)
may be continued for an additional 14 days if complete
remission is not obtained
(in this case: total dose 5,600 units/kg)

n/a5:

6,000-12,000 units/m2 IM daily on day 1

(total dose 6,000-12,000 units/m2)

2-3 weeks5:

10,000-40,000 units IV daily on day 1

(total dose per cycle 10,000-40,000 units)

3 weeks5:

5,000-10,000 units/m2/day IV daily on days 1-7 inclusive

(total dose per cycle 35,000-70,000 m2)

A test dose is often recommended prior to the first dose of asparaginase, or prior to restarting therapy, when there
has been an interval of several days since the last dose.5

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

Page 7 of 9

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Asparaginase

BCCA usual dose noted in bold, italics

Cycle Length:
7
1 week :

6,000 units/m2 IV or IM for one dose on days 1, 3, and 5 for

three weeks
2
(total dose per cycle 54,000 units/m )
Therapy may be further intensified as per protocol.
When Erwinia asparaginase is used following a hypersensitivity reaction to asparaginase, dosing is different due to
14
the different pharmacokinetic profiles. Generally, each dose of asparaginase should be replaced with a single dose
2
of 20,000 units/m of Erwinia asparaginase. For intermittent therapy, Erwinia asparaginase treatment should be
7
resumed at a low dose, 10 units/kg/day, and increased to the full dose over five days if tolerated.

Intravenous/intramuscular
Erwinia asparaginase:

Intravenous/intramuscular
pegaspargase:

15
2 weeks :

2,500 units/m2 IV or IM for one dose on day 1

Note: pegaspargase is not to be given direct IV.

Concurrent radiation:

not given20

Dosage in myelosuppression:

modify according to protocol by which patient is being treated; if no guidelines

available, refer to Appendix 6 "Dosage Modification for Myelosuppression"

Dosage in renal failure:

no adjustment required

Dosage in hepatic failure:

discontinue16

Dosage in dialysis:

no information found

Children:
Intravenous/intramuscular
L-asparaginase or
Erwinia L-asparaginase:
Intravenous pegaspargase:

Cycle Length:
1 week9:
6,000-10,000 units/m2 IV or IM for one dose on days 1, 3, and 5

1-4 weeks9:

2,500 units/m2 IV or IM once daily on day 1

38
Note: often 2 or 3 syringes are required for a single IM dose.
Note: pegaspargase is not to be given direct IV.

REFERENCES:
1. McEvoy GK. AHFS 2006 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; 2006. p.
932-934.
2. MARTINDALE - The Complete Drug Reference (database on the Internet). Asparaginase. Thomson MICROMEDEX, 2006.
Available at: www.micromedex.com. Accessed 4 October 2006.
3. Merck & Co Inc. Elspar Product Monograph. West Point, Pennsylvania; 2000.
4. Graham ML. Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev 2003;55(10):1293-302.
5. Rose BD editor. Asparaginase: Drug Information. UpToDate 14.2 ed. Waltham, Massachusetts: UpToDate; 2006.
6. Ettinger LJ, Ettinger AG, V A, et al. Acute Lymphoblastic Leukaemia A Guide to Asparaginase and Pegaspargase Therapy.
Biopharmaceuticals 1997;1:30-39.
7. Orphan Pharma International. Erwinase Product Monograph. Limonest, France; 2005.
8. Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia: Lippincott - Raven; 2002. p. 281-283.
9. Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia: Lippincott - Raven; 2002. p. 248.
10. Vieira Pinheiro JP. The best way to use asparaginase in childhood acute lymphatic leukaemia - still to be defined? bjh
2004;125:117-127.
11. Rose BD editor. Pegaspargase: Drug Information. UpToDate 14.2 ed. Waltham, Massachusetts: UpToDate; 2006.
12. Avramis VI, Panosyan EH. Pharmacokinetic/Pharmacodynamic Relationships of Asparaginase Formulations. Clin
Pharmacokinet 2005;44(4):367-393.
13. Leukemia/Bone Marrow Transplantation Program of British Columbia. (NHL98-01) Treatment of Lymphoblastic Lymphoma.
Vancouver, British Columbia: BC Cancer Agency; 10 May 2004.

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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Asparaginase

14. Catherine Lambermont. Pharmacovigilance & Medical Information Manager. OPi SAS; 19 September 2006.
15. Enzon Pharmaceuticals Inc. Oncaspar Product Monograph. Bridgewater, New Jersey; 2003.
16. Orphan Pharma International. Kidrolase Product Monograph. Limonest, France; 2005.
17. Maharaj K. Raina PhD. Director Medical Information, Enzon Pharmaceuticals. Personal communication; 2 October 2006.
18. McEvoy GK. AHFS 2006 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; 2006.
p. 1166-1168.
19. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 5th ed. Baltimore, Maryland: Williams and Wilkins; 1998.
20. Kevin Song MD. Personal communication. Hematologist, BMT/Leukemia Group Vancouver General Hospital, BC; December
2006.
21. Duval M, Suciu S, Ferster A, et al. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of
childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer--Children's Leukemia Group phase 3 trial. Blood 2002;99(8):2734-2739.
22. BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and
Management of Extravasation of Chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 February 2004.
23. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in
Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.
24. Feinberg WM, Swenson MR, Feinberg WM, et al. Cerebrovascular complications of L-asparaginase therapy. Neurology
1988;38(1):127-33.
25. DeVita VT, Hellman S, Rosenberg SA. Cancer Principles & Practice of Oncology. 6th ed. Philadelphia: Lippincott Williams &
Wilkins; 2001. p. 454-455.
26. Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia: Lippincott - Raven; 2002. p. 1190.
27. Robert Sarrazin B Pharm. Personal communication. Consultant, OPi Inc; February 2005.
28. Trissel LA. Handbook on Injectable Drugs. 13th ed. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc;
2005. p. 159-160.
29. Roberta Esau. Personal Communication. Pharmacist, British Columbia Children's Hospital, Oncology/Hematology Clinic; 11
December 2006.
30. Robert Sarrazin B Pharm. Personal communication. Consultant, OPi Inc; November 2005.
31. Robert Sarrazin B. Pharm. Personal communication. EUSA Pharma (Canada) Inc.; 17 April 2013.
32. Robert Sarrazin B. Pharm. Personal communication. EUSA Pharma (Canada) Inc.; 22 April 2013.
33. CGF Pharmatec for EUSA Pharma. KIDROLASE product monograph. Montreal, Quebec; 17 April 2008.
34. CGF Pharmatec for EUSA Pharma. ERWINASE for Injection product monograph. Montreal, Quebec; 30 April 2008.
35. Sigma-Tau Pharmaceuticals Inc. ONCASPAR full prescribing information. Gaithersburg, Maryland, USA; March 2011.
36. Dorr RT, Von-Hoff DD. Drug monographs. Cancer chemotherapy handbook. 2nd ed. Norwalk, Conneticut: Appleton and Lange;
1994. p. 201-208.
37. Leukemia/Bone Marrow Transplantation Program of British Columbia. (ALL89-01A) Treatment of Acute Lymphoblastic
Leukemia Induction Cycle 1. Vancouver, British Columbia: BC Cancer Agency; 26 November 2004.
38. Roberta Esau. Personal Communication. Pharmacist, British Columbia Children's Hospital, Oncology/Hematology Clinic; 15
October 2006.

BC Cancer Agency Cancer Drug Manual

Developed: September 1994
Revised: January 2007
Limited revision: May 2007, 1 June 2013

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