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Erwinaze

Generic Name: Asparaginase (Erwinia chrysanthemi)
Class: Antineoplastic Agents
Molecular Formula: C1546H2510N432O476S9 (monomer)
CAS Number: 1349719-22-7

Introduction

Antineoplastic agent; enzyme derived from Erwinia chrysanthemi (formerly Erwinia carotovora; also known as Pectobacterium chrysanthemi).1 6

Uses for Erwinaze

Acute Lymphocytic Leukemia (ALL)

Component of combination chemotherapy for treatment of ALL in patients who are hypersensitive to E. coli-derived asparaginase (native [nonconjugated] asparaginase [Escherichia coli] or pegaspargase; asparaginase [Escherichia coli] no longer commercially available in the US); designated an orphan drug by FDA for this use.1 2 4 6 7 8 9

Erwinaze Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.1 11

Hypersensitivity Reactions

  • Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis.1 (See Hypersensitivity Reactions under Cautions.)

Administration

IM Administration

Administer by IM injection.1

Do not give >2 mL at one injection site.1

Discard powder for injection if foreign particulate matter or discoloration present prior to reconstitution.1

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.1 Based on indicated dosage of drug, reconstitute appropriate number of vials.1

Slowly inject diluent against inner wall of vial; do not forcefully inject directly onto or into powder.1 Dissolve contents by gently mixing or swirling vial; do not shake or invert vial.1

Withdraw appropriate dose from vial into a polypropylene syringe within 15 minutes of reconstitution.1 Administer reconstituted solution within 4 hours or discard; do not freeze or refrigerate reconstituted solution.1

Reconstituted solution should be clear and colorless; discard if particles or protein aggregates visible.1

Discard any unused portion of vial.1

Dosage

Dosage expressed in terms of international units (IU, units).1

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

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.1

To substitute for a dose of native (nonconjugated) asparaginase (Escherichia coli): 25,000 units/m2 for each scheduled dose of native asparaginase (Escherichia coli).1

Dosage Modification for Toxicity and Contraindications to Continued Therapy
Anaphylaxis and Allergic Reactions

Discontinue drug if serious allergic reaction occurs.1

Thrombosis and Hemorrhage

Withhold drug if thrombotic or hemorrhagic event occurs; may resume therapy after resolution.1 (See Contraindications under Cautions.)

Pancreatitis

Permanently discontinue drug if severe pancreatitis occurs.1 (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.1

Adults

ALL
ALL and Hypersensitivity to Escherichia coli-derived Asparaginase
IM

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.1

To substitute for a dose of native (nonconjugated) asparaginase (Escherichia coli): 25,000 units/m2 for each scheduled dose of native asparaginase (Escherichia coli).1

Dosage Modification for Toxicity and Contraindications to Continued Therapy
Anaphylaxis and Allergic Reactions

Discontinue drug if serious allergic reaction occurs.1

Thrombosis and Hemorrhage

Withhold drug if thrombotic or hemorrhagic event occurs; may resume therapy after resolution.1 (See Contraindications under Cautions.)

Pancreatitis

Permanently discontinue drug if severe pancreatitis occurs.1 (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.1

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.1

Renal Impairment

Manufacturer makes no specific dosage recommendations.1

Geriatric Patients

Safety and efficacy not established in geriatric patients.1

Cautions for Erwinaze

Contraindications

  • History of serious thrombosis with prior asparaginase therapy.1

  • History of serious pancreatitis with prior asparaginase therapy.1

  • History of serious hemorrhagic events with prior asparaginase therapy.1

  • History of serious hypersensitivity reactions (e.g., anaphylaxis) to asparaginase (Erwinia chrysanthemi).1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported.1 Allergic reactions reported in some patients switching to asparaginase (Erwinia chrysanthemi) following clinical hypersensitivity to native asparaginase (Escherichia coli).6 7 8 9

Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis.1

If serious hypersensitivity reaction occurs, discontinue drug and initiate appropriate therapy.1

Pancreatitis

Pancreatitis, including grade 3 or 4, reported.1 Evaluate patients experiencing symptoms compatible with pancreatitis to establish a diagnosis.1

In patients with severe or hemorrhagic pancreatitis associated with abdominal pain for >72 hours and amylase concentrations ≥2 times ULN, discontinue drug.1 Severe pancreatitis is a contraindication to continued therapy.1

In patients with mild pancreatitis, withhold drug until signs and symptoms resolve and amylase concentrations return to normal; may resume therapy after resolution.1

Hyperglycemia

Glucose intolerance (sometimes irreversible) and hyperglycemia (including grade 3 or 4) reported.1

Monitor glucose concentrations at baseline and periodically during therapy.1 Administer insulin as necessary.1

Thrombosis and Hemorrhage

Serious thrombotic events, including sagittal sinus thrombosis, reported.1 Coagulation proteins (i.e., antithrombin III, fibrinogen, protein C activity, protein S activity) decreased in most patients after 2 weeks of therapy.1

If thrombotic or hemorrhagic event occurs, withhold drug until symptoms resolve; may resume therapy after resolution.1

Immunogenicity

Potential for immunogenicity with use of therapeutic proteins such as asparaginase (Erwinia chrysanthemi).1 Insufficient data available to characterize incidence of antibodies to asparaginase (Erwinia chrysanthemi).1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether asparaginase (Erwinia chrysanthemi) is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy as a component of combination chemotherapy for ALL evaluated in a safety and clinical pharmacology study in patients 2–18 years of age (median: 10 years of age) who were hypersensitive to E. coli-derived asparaginase.1

Geriatric Use

Safety and efficacy not established in geriatric patients.1

Common Adverse Effects

Serious hypersensitivity reactions (e.g., anaphylaxis, urticaria), pancreatitis, abnormal transaminases, thrombosis, fever, hyperglycemia, nausea, vomiting.1

Interactions for Erwinaze

No formal drug interaction studies to date.1

Erwinaze Pharmacokinetics

Distribution

Extent

Not known whether asparaginase (Erwinia chrysanthemi) is distributed into milk.1

Elimination

Half-life

Approximately 0.65 days.4 5 6 Appears to be shorter than that of native asparaginase (Escherichia coli) or pegaspargase (conjugate of polyethylene glycol [PEG] and E. coli-derived asparaginase).4 5 6

Stability

Storage

Parenteral

Powder for Injection

2–8°C; protect from light.1

Reconstituted solution: Use within 4 hours or discard; do not freeze or refrigerate reconstituted solution.1

Discard any unused portion.1

Actions

  • Inactivates the amino acid asparagine, which is required by tumor cells for protein synthesis.1 8 10

  • Catalyzes deamidation of asparagine to aspartic acid and ammonia, which reduces circulating concentrations of asparagine and leads to leukemic cell death.1 8 10

  • Antigenically distinct from asparaginase (Escherichia coli).6

Advice to Patients

  • Risk of hypersensitivity reactions, including the possibility of anaphylaxis.1 Importance of informing patients of the symptoms of allergic reactions, including anaphylaxis, and instructing them to immediately contact clinicians if such symptoms occur.1

  • Risk of pancreatitis.1 Importance of immediately informing clinicians if abdominal pain occurs.1

  • Risk of glucose intolerance.1 Importance of informing clinicians if excessive thirst or any increase in the volume or frequency of urination occurs.1

  • Risk of thrombosis and hemorrhage.1 Importance of immediately informing clinicians if headache, arm or leg swelling, shortness of breath, or chest pain occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (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.

Asparaginase (Erwinia chrysanthemi)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IM use

10,000 units

Erwinaze

EUSA

AHFS DI Essentials. © Copyright 2016, Selected Revisions August 2, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. EUSA Pharma (USA), Inc. Erwinaze (asparaginase Erwinia chrysanthemi) intramuscular injection prescribing information. Langhorne, PA; 2011 Nov.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2012 Apr 23.

3. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125359Orig1s000: Summary review. From FDA website. Accessed 2012 Apr 23.

4. Childhood acute lymphoblastic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2012 May 18.

5. Asselin BL, Whitin JC, Coppola DJ et al. Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol. 1993; 11:1780-6. [PubMed 8355045]

6. Vrooman LM, Supko JG, Neuberg DS et al. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2010; 54:199-205. [PubMed 19672973]

7. Pieters R, Hunger SP, Boos J et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011; 117:238-49. [PubMed 20824725]

8. van den Berg H. Asparaginase revisited. Leuk Lymphoma. 2011; 52:168-78. [PubMed 21281233]

9. Raetz EA, Salzer WL. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010; 32:554-63. [PubMed 20724951]

10. Lundbeck Inc. Elspar (asparaginase Escherichia coli) intravenous or intramuscular prescribing information. Deerfield, IL; 2010 Apr.

11. Lundbeck Inc. Elspar material safety data sheet. Deerfield, IL; 2010 Apr 1.

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