Asparaginase (Erwinia chrysanthemi) (Monograph)

Brand name: Erwinaze
Drug class: Antineoplastic Agents
Molecular formula: C₁₅₄₆H₂₅₁₀N₄₃₂O₄₇₆S₉ (monomer)
CAS number: 1349719-22-7

Medically reviewed by Drugs.com on Apr 17, 2024. Written by ASHP.

Introduction

Antineoplastic agent; enzyme derived from Erwinia chrysanthemi (formerly Erwinia carotovora; also known as Pectobacterium chrysanthemi).

Uses for Asparaginase (Erwinia chrysanthemi)

Acute Lymphocytic Leukemia (ALL)

Component of combination chemotherapy for treatment of ALL in patients who are hypersensitive to E. coli-derived asparaginase preparations; designated an orphan drug by FDA for this use.

Asparaginase (Erwinia chrysanthemi) Dosage and Administration

General

• Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis. (See Hypersensitivity Reactions under Cautions.)

• In patients receiving the drug by IV infusion, consider monitoring serum trough asparaginase activity; if desired asparaginase concentrations not achieved, consider switching to IM administration. (See Plasma Concentrations under Pharmacokinetics.)

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.

Administration

Administer by IM injection or IV infusion.

IM Administration

Do not give >2 mL at one injection site.

Reconstitution

Discard powder for injection if foreign particulate matter or discoloration present prior to reconstitution.

Add 1 or 2 mL of sterile, preservative-free 0.9% sodium chloride injection to a vial containing 10,000 units of asparaginase (Erwinia chrysanthemi) to provide a solution containing 10,000 or 5000 units/mL, respectively. Based on indicated dosage of drug, reconstitute appropriate number of vials.

Slowly inject diluent against inner wall of vial; do not forcefully inject directly onto or into powder. Dissolve contents by gently mixing or swirling vial; do not shake or invert vial.

Withdraw appropriate dose from vial into a polypropylene syringe within 15 minutes of reconstitution. Administer reconstituted solution within 4 hours or discard; do not freeze or refrigerate reconstituted solution.

Reconstituted solution should be clear and colorless; discard if particles or protein aggregates visible.

Discard any unused portion of vial.

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Must be reconstituted and further diluted prior to IV administration.

Do not infuse simultaneously through the same IV line with other drugs.

Reconstitution

Reconstitute asparaginase (Erwinia chrysanthemi) lyophilized powder in the same manner as for IM administration. (See IM Administration: Reconstitution, under Dosage and Administration.)

Dilution

Slowly inject the appropriate volume of reconstituted asparaginase (Erwinia chrysanthemi) solution into an IV infusion bag containing 100 mL of 0.9% sodium chloride injection at room temperature. Do not shake or squeeze bag.

Rate of Administration

Administer dose by IV infusion over 1–2 hours.

Dosage

Dosage expressed in terms of international units (IU, units).

Consult published protocols for dosage, method of administration, and administration sequence of drugs in combination regimens.

Pediatric Patients

ALL

ALL and Hypersensitivity to Escherichia coli-derived Asparaginase

IM or IV

To substitute for a dose of pegaspargase: 25,000 units/m² 3 times weekly (Monday, Wednesday, Friday) for 6 doses for each planned dose of pegaspargase.

To substitute for a dose of native (nonconjugated) asparaginase (Escherichia coli) (no longer commercially available in US): 25,000 units/m² for each scheduled dose of native asparaginase (Escherichia coli).

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Anaphylaxis and Allergic Reactions

Discontinue drug if serious allergic reaction occurs.

Thrombosis and Hemorrhage

Withhold drug if thrombotic or hemorrhagic event occurs; may resume therapy after resolution. (See Contraindications under Cautions.)

Pancreatitis

Permanently discontinue drug if severe pancreatitis occurs. (See Pancreatitis under Cautions.)

If mild pancreatitis occurs, withhold drug until signs and symptoms resolve and amylase concentrations return to normal; may resume therapy after resolution.

Adults

ALL

ALL and Hypersensitivity to Escherichia coli-derived Asparaginase

IM or IV

To substitute for a dose of pegaspargase: 25,000 units/m² 3 times weekly (Monday, Wednesday, Friday) for 6 doses for each planned dose of pegaspargase.

To substitute for a dose of native (nonconjugated) asparaginase (Escherichia coli) (no longer commercially available in US): 25,000 units/m² for each scheduled dose of native asparaginase (Escherichia coli).

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Anaphylaxis and Allergic Reactions

Discontinue drug if serious allergic reaction occurs.

Thrombosis and Hemorrhage

Withhold drug if thrombotic or hemorrhagic event occurs; may resume therapy after resolution. (See Contraindications under Cautions.)

Pancreatitis

Permanently discontinue drug if severe pancreatitis occurs. (See Pancreatitis under Cautions.)

If mild pancreatitis occurs, withhold drug until signs and symptoms resolve and amylase concentrations return to normal; may resume therapy after resolution.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Safety and efficacy not established in geriatric patients.

Cautions for Asparaginase (Erwinia chrysanthemi)

Contraindications

• History of serious thrombosis with prior asparaginase therapy.

• History of serious pancreatitis with prior asparaginase therapy.

• History of serious hemorrhagic events with prior asparaginase therapy.

• History of serious hypersensitivity reactions (e.g., anaphylaxis) to asparaginase (Erwinia chrysanthemi).

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious (grade 3 or 4) hypersensitivity reactions, including anaphylaxis, reported. Allergic reactions reported in some patients switching to asparaginase (Erwinia chrysanthemi) following clinical hypersensitivity to native (nonconjugated) asparaginase (Escherichia coli) (no longer commercially available in US).

Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis.

If serious hypersensitivity reaction occurs, discontinue drug and initiate appropriate therapy.

Pancreatitis

Pancreatitis, including grade 3 or 4, reported. Evaluate patients experiencing symptoms compatible with pancreatitis to establish a diagnosis.

In patients with severe or hemorrhagic pancreatitis associated with abdominal pain for >72 hours and amylase concentrations ≥2 times ULN, discontinue drug. Severe pancreatitis is a contraindication to continued therapy.

In patients with mild pancreatitis, withhold drug until signs and symptoms resolve and amylase concentrations return to normal; may resume therapy after resolution.

Hyperglycemia

Glucose intolerance (sometimes irreversible) and hyperglycemia (including grade 3 or 4) reported.

Monitor glucose concentrations at baseline and periodically during therapy. Administer insulin as necessary.

Thrombosis and Hemorrhage

Serious thrombotic events (e.g., sagittal sinus thrombosis, pulmonary embolism) reported. Coagulation proteins (i.e., antithrombin III, fibrinogen, protein C activity, protein S activity) decreased in most patients after 2 weeks of therapy.

If thrombotic or hemorrhagic event occurs, withhold drug until symptoms resolve; may resume therapy after resolution.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. Embryofetal mortality and fetal structural abnormalities reported in animal studies at doses lower than maximum recommended human dosage.

Confirm pregnancy status prior to initiating asparaginase (Erwinia chrysanthemi) therapy. Avoid pregnancy during therapy. Women of childbearing potential should use effective methods of contraception while receiving asparaginase (Erwinia chrysanthemi) and for ≥3 months after last dose. Avoid concomitant use of oral contraceptives and asparaginase (Erwinia chrysanthemi). (See Specific Drugs under Interactions.) If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Immunogenicity

Potential for immunogenicity with use of therapeutic proteins such as asparaginase (Erwinia chrysanthemi). Anti-drug antibodies reported. Presence of anti-drug antibodies is associated with higher risk of hypersensitivity reactions in patients receiving the drug by IV infusion compared with those receiving the drug by IM injection.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether asparaginase (Erwinia chrysanthemi) distributes into milk or has any effects on milk production or on the nursing infant. Women should not breast-feed during therapy and for ≥3 months after last dose.

Pediatric Use

Safety and efficacy as a component of combination chemotherapy for ALL established in pediatric patients ≥1 year of age who were hypersensitive to E. coli-derived asparaginase.

Geriatric Use

Safety and efficacy not established in geriatric patients.

Common Adverse Effects

Systemic hypersensitivity reactions, hyperglycemia, aminotransferase abnormalities, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain or discomfort, diarrhea.

Drug Interactions

No formal drug interaction studies to date.

Specific Drugs

Asparaginase (Erwinia chrysanthemi) Pharmacokinetics

Absorption

Plasma Concentrations

Serum trough asparaginase activity of ≥0.1 units/mL correlates with asparagine depletion; has been established as a surrogate measure of asparaginase efficacy.

Proportion of patients with sustained asparaginase activity is lower following IV infusion compared with IM injection. (See Table 1.)

Distribution

Extent

Not known whether asparaginase (Erwinia chrysanthemi) is distributed into milk.

Elimination

Half-life

Mean half-life of 15.6 hours following IM administration and 7.51 hours following IV infusion. (See Plasma Concentrations under Pharmacokinetics.)

Appears to be shorter than that of native (nonconjugated) asparaginase (Escherichia coli) (no longer commercially available in US) or pegaspargase (conjugate of monoethoxy polyethylene glycol [mPEG] and E. coli-derived asparaginase).

Stability

Storage

Parenteral

Powder for Injection

2–8°C; protect from light.

Reconstituted solution: Use within 4 hours or discard; do not freeze or refrigerate reconstituted solution.

Discard any unused portion.

Compatibility

Parenteral

Solution Compatibility1

Actions

• Inactivates the amino acid asparagine, which is required by tumor cells for protein synthesis.

• Catalyzes deamidation of asparagine to aspartic acid and ammonia, which reduces circulating concentrations of asparagine and leads to leukemic cell death.

• Antigenically distinct from asparaginase (Escherichia coli).

Advice to Patients

• Risk of hypersensitivity reactions, including the possibility of anaphylaxis. Importance of informing patients of the symptoms of allergic reactions, including anaphylaxis, and instructing them to immediately contact clinicians if such symptoms occur.

• Risk of pancreatitis. Importance of immediately informing clinicians if abdominal pain occurs.

• Risk of glucose intolerance. Importance of informing clinicians if excessive thirst or any increase in the volume or frequency of urination occurs.

• Risk of thrombosis and hemorrhage. Importance of immediately informing clinicians if headache, arm or leg swelling, shortness of breath, or chest pain occurs.

• Risk of fetal harm. Importance of women informing clinicians if they are or plan to become pregnant. Necessity of advising women of reproductive potential that they should use effective methods of contraception while receiving the drug and for ≥3 months after the last dose. Importance of advising women that concomitant use of asparaginase (Erwinia chrysanthemi) and oral contraceptives is not recommended.

• Importance of advising women to avoid breast-feeding while receiving asparaginase (Erwinia chrysanthemi) and for ≥3 months after the last dose.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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