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drug-monograph
pegaspargase
Cancer Type
Hematologic,
Leukemia - Acute Lymphoblastic (ALL),
Lymphoma - T-cell
Other Names
Oncaspar®
Appearance
Clear solution for injection; may be mixed into larger bags of fluids
Funding Program
High Cost Therapy Funding Program
New Drug Funding Program
B - Mechanism of Action and Pharmacokinetics
Pegaspargase is a pegylated form of L-asparaginase. It hydrolyzes extracellular L-asparagine, an amino acid that appears to be essential for protein synthesis by some tumour cells, which are unable to synthesize asparagine. Pegylation does not change L-asparaginase's enzymatic properties, but affects its pharmacokinetics and immunogenicity. Pegaspargase is less immunogenic than asparaginase derived from E. coli or Erwinia chrysanthemi; however, cross-hypersensitivity (including anaphylaxis) can occur. Pegaspargase has immunosuppressive activity.
Absorption
| Bioavailability | 82% (after first IM dose), 98% (after repeat IM dosing) |
| T max | 5 days (single IM dose); 1.25 h (single IV dose) |
Distribution
| Cross blood brain barrier? | Distribution in to the CSF is reported to be similar to L-asparaginase (minimal). |
Metabolism
Degraded by enzymes distributed ubiquitously in tissues.
| Active metabolites | None known |
| Inactive metabolites | Yes |
Elimination
Half-life appeared to be unaffected by dose, age, sex, BSA, renal or hepatic function. Pegaspargase is not excreted renally. Terminal half-life was shorter in hypersensitive patients than in non-hypersensitive patients, which may be due to the formation of high levels of anti-drug antibodies
| Half-life | IM: 5.8 days; IV: 5.3 days |
C - Indications and Status
Health Canada Approvals:
Other Uses:
- Acute lymphoblastic leukemia
Refer to the product monograph for a full list of approved indications.
Other Uses:
- Extranodal natural killer/T-cell lymphoma (ENKTL)
D - Adverse Effects
Emetogenic Potential:
Minimal
Extravasation Potential: None
The following adverse events were reported from clinical trials (including pediatric patients) with pegaspargase and post-marketing reports. The list also includes severe or life-threatening events reported with other asparaginase formulations.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arterial thromboembolism (1 to <10%) | E | |||
| Hypotension (3%) (severe) | I | ||||
| Venous thromboembolism (3%) (including CNS) | E | ||||
| Dermatological | Rash (5%) (severe skin disorders) | E | |||
| Gastrointestinal | Abdominal pain (≥10%) | E | |||
| Diarrhea (≥10%) | E | ||||
| GI perforation (rare) | E | ||||
| Mucositis (1 to <10%) | E | ||||
| Nausea, vomiting (1 to <10%) | I | ||||
| General | Fever (may be severe) | I | |||
| Hematological | Fibrinogen decreased (1 to <10%; also ↑ PT, aPTT ± bleeding; may be severe, including CNS) | E | |||
| Myelosuppression (1 to <10%; ± infection) | E | ||||
| Hepatobiliary | ↑ LFTs (≥10%) (may be severe with hepatic failure) | E | |||
| Pancreatitis (≥10%) (2% severe, including hemorrhagic or necrotizing) | E D | ||||
| Veno-occlusive disease (rare) | E | ||||
| Hypersensitivity | Hypersensitivity (10%) (in asparaginase-naive patients; may be severe) | I | |||
| Immune | Antibody response (antibody formation; 2-11%) | E D | |||
| Metabolic / Endocrine | Hyperglycemia (≥10%) (5% severe) | E | |||
| Hyperlipidemia (1 to <10%) | E | ||||
| Hyperuricemia (during periods of active cell lysis) | I | ||||
| Musculoskeletal | Musculoskeletal pain (1 to <10%) | E | |||
| Nervous System | Cognitive disturbance (1 to <10%) | E | |||
| Peripheral neuropathy (7%) (severe) | E | ||||
| Posterior reversible encephalopathy syndrome (PRES) (rare) | E | ||||
| Seizure (1 to <10%) | E | ||||
| Tremor (rare) | E | ||||
| Renal | Nephrotoxicity (rare) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
Hyperuricemia during periods of active cell lysis, which is caused by cytotoxic chemotherapy of highly proliferative tumours of massive burden (e.g. some leukemias and lymphomas), can be minimized with allopurinol and hydration. In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids, if tumour lysis is expected.
Severe hepatotoxicity has been described when used in combination with other hepatotoxic agents and in debilitated patients . Asparaginase treatment may increase pre-existing liver impairment from underlying liver disease or caused by prior therapy. Liver abnormalities usually resolve after the end of therapy and some reversal may occur during the course of treatment.
Asparaginase or hepatic impairment may produce decreased levels of factors V, VII, VIII, IX, X and fibrinogen, and possibly contribute to coagulation disorders. Increased fibrinolytic activity has also been observed.
Hemorrhagic and thrombotic cardiovascular or neurologic events occur in approximately 1-2% of patients receiving asparaginase. These generally occur after a few weeks of l-asparaginase therapy, and may occur after therapy is completed.
Cognitive dysfunction may include mild to severe lethargy, drowsiness, depression, confusion, hallucination, agitation, seizures or personality changes. They are seen during the first day of therapy and resolve within a few days to a week after drug discontinuation.
Pancreatitis can occur during or after therapy, and can be fatal. It may be present despite normal serum amylase concentrations.
Hepatotoxicity, including severe, potentially fatal cases of hepatic veno-occlusive disease (VOD), has been reported in patients who received pegaspargase with standard chemotherapy, including during induction phase of multiphase chemotherapy.
Hyperglycemia has been observed, which appears to be potentiated by prednisone. Transient diabetes mellitus may develop. Insulin may be required for severe hyperglycemia, but it is usually reversible when the drug is discontinued. Glucose intolerance may be irreversible.
Severe hypersensitivity reactions may occur with pegaspargase. There is a higher risk in patients with known hypersensitivity to other forms of L-asparaginase.
Antibodies to pegaspargase have been observed. Patients with hypersensitivity reactions to asparaginase were more likely to have antibodies than those who did not have reactions. Hypersensitivity reactions are associated with increased asparaginase clearance, and higher antibody levels may lead to decreased asparaginase activity.
E - Dosing
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Different asparaginase products are not interchangeable and dosing schedules are different.
May be given either by intravenous or intramuscular injection.
Numerous dosing schedules exist. Refer to protocol by which the patient is being treated.
Usually used in combination with other cytotoxic drugs.
Thromboprophylaxis may be considered.
Premedications (prophylaxis for infusion reaction)
Give 30-60 minutes before administration:
- Acetaminophen (e.g. 500 mg PO)
- H1-receptor blocker (e.g. diphenhydramine 50 mg PO)
- H2-receptor blocker (e.g. famotidine 20 mg IV)
- Corticosteroid (e.g. hydrocortisone 100 mg IV)
Adults:
- 2000 units/m² q14-21 days
- 2500 units/m2 q21 days (SMILE or DDGP)
Consider monitoring trough serum L-asparaginase activity measured before the next pegaspargase administration. A switch to a different L-asparaginase preparation could be considered if L-asparaginase activity failed to reach target levels. Consult with a hematology expert.
Dosage with Toxicity:
Dosage with Myelosuppression: No dose adjustment required.
- Myelosuppression is not increased when used with other antileukemic drugs.
Dosage with Other Toxicity:
| Toxicity | Severity | Action |
| Thrombosis | Uncomplicated deep vein thrombosis | Hold; treat with appropriate antithrombotic therapy. Restart when resolved if appropriate while continuing antithrombotic therapy. |
| Severe or life-threatening | Discontinue and manage appropriately. | |
| Hemorrhagic events | Grade 3 to 4 | Hold; evaluate for coagulopathy and consider clotting factor replacement as needed. Restart with the next scheduled dose if bleeding is controlled. |
| Lipase or amylase increased | Grade 3 to 4 | If >3 x ULN, hold until lipase or amylase levels stabilize or are declining. Discontinue if pancreatitis is confirmed. |
Bilirubin increased |
>3 to 10 x ULN | Hold; restart if resolved to bilirubin ≤1.5 x ULN. |
| >10 x ULN | Discontinue. | |
| Veno-occlusive disease | Any | Discontinue. |
| Severe hypersensitivity reactions, anaphylaxis | ||
| RPLS / PRES | ||
| Other grade 4 organ/ non-hematologic |
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
IV Pegaspargase:
Grade |
Management |
Re-challenge |
1 |
|
|
2 |
Restart:
|
|
3 or 4 |
|
|
Dosage with Hepatic Impairment:
Not formally studied in patients with hepatic impairment. May increase pre-existing liver impairment. There is an increased risk of hepatic effects (e.g. ↑ LFTs or bilirubin) among patients > 18 years of age.
| Hepatic Impairment | LFTs | Starting dose |
| Mild | bilirubin ≤ 3 x ULN ± AST/ALT ≤ 10 x ULN | No information found |
| Moderate | ||
| Severe |
bilirubin > 3 x ULN ± AST/ALT > 10 x ULN | Contraindicated |
Dosage with Renal Impairment:
Not formally studied in patients with renal impairment. Pegaspargase is not excreted renally; no dose adjustment is required.
Dosage in the elderly:
There are limited data available for patients > 65 years.
Children:
Refer to protocol by which the patient is being treated. There is very limited information on safety and efficacy of pegaspargase in children < 1 year of age.
F - Administration Guidelines
Risk of medication error: The 3 asparaginase formulations (pegaspargase, E. coli asparaginase, Erwinia asparaginase) are not Interchangeable. Confirm the formulation carefully against the regimen used before prescribing, dispensing and administration.
- May be given either IV or IM
- For IV administration, dilute the dose in 100 NS or D5W and infuse over 1 to 2 hours.
- The IM injection volume should not exceed 3 mL in adults (or 2 mL in children/adolescents) per injection site; divide the dose and give at several injection sites for higher injection volumes.
- Refrigerate unused vials (2 to 8ºC). Do not freeze or shake. Protect from light.
G - Special Precautions
Contraindications:
Other Drug Properties:
- Anaphylactic or severe hypersensitivity reactions to the active substance or to any of the excipients
- Known serious allergic reactions to pegaspargase
- Patients with known serious thrombosis or serious hemorrhagic events with previous L-asparaginase therapy
- Patients who have or had pancreatitis (including hemorrhagic)
- Severe hepatic impairment (bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN).
- Avoid live and attenuated live vaccines.
- Pegaspargase may worsen pre-existing liver impairment.
- Use with caution in diabetic patients.
- Risk of severe hypersensitivity reactions is higher in patients with known hypersensitivity to other forms of asparaginase.
- Patients should use caution when driving or using machinery as drowsiness, dizziness, confusion, or seizures have been reported with treatment.
Other Drug Properties:
- Carcinogenicity: No information available
- Mutagenicity: Not observed in vitro
- Embryotoxicity:
- Documented in animals with L-asparaginase.
- Teratogenicity:
- Documented in animals with L-asparaginase.
- Pregnancy:
- Pegaspargase is contraindicated in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 6 months after the last dose.
- Since an indirect interaction between oral contraceptives and pegaspargase cannot be excluded, patients who can become pregnant should use a method other than oral contraceptives.
- Breastfeeding:
- Breastfeeding is not recommended during treatment and for 1 month after the last dose.
- Fertility effects: No information available
H - Interactions
No formal drug interaction studies have been conducted with pegaspargase. Pegaspargase may interfere with enzymatic metabolism of other medications, especially in the liver.
A decrease in serum proteins caused by asparaginase products may increase the toxicity of other medications that are protein bound.
Thyroid function test results may be affected. A reduction in thyroxin-binding globulin has been reported within 2 days after the first dose of L-asparaginase and returned to pre-treatment levels within 4 weeks after the last dose.
The following drug interactions have been observed with various asparaginase products.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Methotrexate (when given before asparaginase) | ↑ effect of both drugs | Synergistic effect | Caution. Refer to protocol by which the patient is being treated. |
| Methotrexate (when given after asparaginase) | ↓ effect of both drugs | Antagonistic effect | Caution. Refer to protocol by which the patient is being treated. |
| Cytarabine (when given before asparaginase) | ↑ effect of asparaginase | Synergistic effect | Caution. Refer to protocol by which the patient is being treated. |
| Cytarabine (when given after asparaginase) | ↓ effect of asparaginase | Antagonistic effect | Caution. Refer to protocol by which the patient is being treated. |
| Antineoplastic agents that are substrates for CYPs | Effects on protein synthesis in liver and reduced clearance may affect metabolism and clearance of these substrates | Caution | |
| Neurotoxic products (e.g. vincristine, methotrexate) | ↑ risk of CNS toxicity | Additive | Monitor |
| Hepatotoxic drugs or drugs metabolized by the liver | ↑ risk of hepatotoxicity | Additive | Monitor liver function; use with caution, especially in patients with pre-existing hepatic impairment |
| Glucocorticoids (e.g. prednisolone, dexamethasone) | ↑ glucocorticoid exposure | Decreased glucocorticoid elimination | Monitor for glucocorticoid adverse effects |
| Glucocorticoids (e.g. prednisolone, dexamethasone) | ↑ risk of glucocorticoid-induced osteonecrosis in children > 10 years of age, higher incidence in girls | Unknown | Monitor |
| Drugs affecting coagulation (e.g. glucocorticoids, methotrexate, daunorubicin, warfarin, heparin, ASA, dipyridamole, NSAIDs) | ↑ tendency to bleeding and/or thrombosis | Alter coagulation parameters | Caution. Monitor coagulation parameters, adjust procoagulant/anticoagulant dose if needed, and manage bleeding/thrombotic risk. |
| Oral contraceptives | May ↓ efficacy of oral contraceptives | Hepatic clearance of oral contraceptives may be reduced | Avoid concomitant use. Use alternative methods of contraception. |
| Live vaccines | ↑ risk of severe infections | Additive immunosuppressive effects of asparaginase, chemotherapy, and underlying condition | Avoid. Live vaccines should not be given during treatment and for at least 3 months after the end of treatment |
| Highly protein-bound drugs | ↑ risk of toxicity from these drugs | Decreased serum proteins | Caution |
| Immunosuppressants | ↑ risk of immunosuppression | Additive | Caution |
I - Recommended Clinical Monitoring
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
| Monitor Type | Monitor Frequency |
|---|---|
Liver function tests, albumin |
Baseline, before each dose, and at least weekly, during treatment cycles that include pegaspargase, until 6 weeks after the last dose (more frequent monitoring with abnormal LFTs or signs of VOD) |
Serum amylase, lipase levels |
Baseline, before each dose, and as clinically indicated |
Clotting profile (PT, aPTT, fibrinogen, ATIII) |
Baseline and as clinically indicated, more frequent if concurrent use of drugs with pro-coagulant/anticoagulant effects |
Blood glucose, especially in patients known to be diabetic |
Baseline and weekly until recovery from the treatment cycle |
CBC |
Baseline and as clinically indicated |
Hypersensitivity reactions |
For 1 hour after administration |
Trough serum L-asparaginase level |
Before the next dose (refer to local protocols) |
Clinical toxicity assessment for tumour lysis syndrome, infection, hypersensitivity reactions, GI, rash, pancreatitis, thromboembolism/bleeding, neurologic effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
| Monitor Type | Monitor Frequency |
|---|---|
Cholesterol and triglycerides |
As clinically indicated |
Urinary glucose |
Baseline and as clinically indicated |
Ammonia levels |
As clinically indicated |
J - Supplementary Public Funding
High Cost Therapy Funding Program (HCTFP website )
- Pegaspargase (Inpatient) - Adult Acute Lymphoblastic Leukemia (ALL) Lymphoblastic Lymphoma Mixed or Biphenotypic Leukemia
- Pegaspargase - Newly Diagnosed Pediatric ALL Lymphoblastic Lymphoma or Mixed_Biphenotypic Leukemia
- Pegaspargase - Relapsed or Refractory Pediatric ALL Lymphoblastic Lymphoma or Mixed_Biphenotypic Leukemia
- Pegaspargase (Outpatient) - Adult Acute Lymphoblastic Leukemia (ALL) Lymphoblastic Lymphoma Mixed or Biphenotypic Leukemia
- Pegaspargase - Extranodal Natural Killer/T-cell Lymphoma
K - References
Avramis VI, Panosyan EH. Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations. Clin Pharmacokinet 2005; 44(4): 367-93.
Heo YA, Syed YY, Keam SJ. Pegaspargase: A review in acute lymphoblastic leukaemia. Drugs 2019 May;79(7):767-77.
McEvoy GK, editor. AHFS Drug Information 2009. Bethesda: American Society of Health-System Pharmacists, p. 935-8, 1207-10.
Prescribing information: Oncaspar® (pegaspargase). Servier Pharmaceuticals (USA), November 2021.
Product Monograph: Kidrolase® (asparaginase). Jazz Pharmaceuticals, December 18, 2017.
Product Monograph: Erwinase® (Erwinia asparaginase). Jazz Pharmaceuticals, July 20, 2016.
Product Monograph: Oncaspar® (pegaspargase). Servier Canada., August 2024.
Silverman LB, Stevenson KE, Athale UH, et al. Results of The DFCI ALL consortium protocol 05-001 for children and adolescents with newly diagnosed ALL. Blood 2013;122(21):838.
Stock W, Luger SM, Advani AS. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019 Apr 4;133(14):1548-59.
Stock W, Douer D, DeAngelo DJ, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma 2011;52(12):2237-53.
May 2026 Updated Adverse Effects, Dosing, Special Precautions, Interactions, and Monitoring sections
L - Disclaimer
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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Last Updated: July 21, 2026
