Asparaginase (Erwinia chrysanthemi) (Recombinant) (Monograph)

Brand name: Rylaze
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Antineoplastic agent; biosynthetic (recombinant DNA origin) preparation of an asparagine-specific enzyme. Structurally similar to native asparaginase Erwinia chrysanthemi.

Uses for Asparaginase (Erwinia chrysanthemi) (Recombinant)

Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Component of combination chemotherapy for treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adults and pediatric patients ≥1 month of age with hypersensitivity to E. coli-derived asparaginase preparations; designated an orphan drug by FDA for treatment of ALL.

Received fast track and priority review from the FDA to alleviate the burden of a global shortage of asparaginase (Erwinia chrysanthemi).

Asparaginase (Erwinia chrysanthemi) (Recombinant) Dosage and Administration

General

Pretreatment Screening

• Verify pregnancy status in females of reproductive potential.

Patient Monitoring

• Monitor bilirubin, transaminases, and glucose concentrations, and perform clinical examinations prior to treatment every 2–3 weeks, and if clinically indicated. If results are abnormal, monitor patients until recovery from the cycle of therapy.

Premedication and Prophylaxis

• Premedicate with acetaminophen, an H₁-receptor blocker, and an H₂-receptor blocker 30-60 minutes before administration in order to reduce the risk and severity of hypersensitivity reactions.

Dispensing and Administration Precautions

• Administer the drug in a setting with resuscitation equipment and other agents necessary to treat anaphylactic reactions.

Administration

IM Administration

Administer by IM injection.

In order to reduce the risk and severity of hypersensitivity reactions, premedicate patients with acetaminophen, an H₁-receptor blocker, and an H₂-receptor blocker 30-60 minutes before administration.

Prior to administration, determine dose, total volume, and number of vials required based on patient's body surface area.

Withdraw appropriate volume of drug (based on indicated dose) into a syringe for injection; more than 1 vial may be required for a full dose.

Do not give >2 mL at one injection site. If IM dose >2 mL, divide the dose and administer at separate sites. Rotate injection sites regularly. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen.

Dosage

Pediatric Patients

ALL or LBL in Patients with Hypersensitivity to E. coli-derived Asparaginase

IM

Children ≥1 month of age: recommended dosage regimen when replacing a long-acting asparaginase product is either 25 mg/m² administered every 48 hours or 25 mg/m² on Monday and Wednesday mornings and 50 mg/m² on Friday afternoon. Administer the Friday afternoon dose 53 to 58 hours after the Wednesday morning dose.

Adults

ALL or LBL in Patients with Hypersensitivity to E. coli-derived Asparaginase

IM

Recommended dosage regimen when replacing a long-acting asparaginase product is either 25 mg/m² administered every 48 hours or 25 mg/m² on Monday and Wednesday mornings and 50 mg/m² on Friday afternoon. Administer the Friday afternoon dose 53 to 58 hours after the Wednesday morning dose.

Recommended Duration of Therapy

Table 1 summarizes the number of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn dosages recommended for the intended duration of treatment for replacement of a single dose of calaspargase pegol products (3 weeks of asparaginase coverage) or a single dose of pegaspargase products (2 weeks of asparaginase coverage). Clinicians should refer to the prescribing information for the long-acting asparaginase product to determine the total duration of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn as replacement therapy.

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Some adverse effects require dosage interruption and/or reduction or discontinuance of therapy based on severity of the adverse reaction (see Table 2).

Special Populations

Dosage in Hepatic Impairment

No specific dosage recommendations; contraindicated in patients with severe hepatic impairment.

Dosage in Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Asparaginase (Erwinia chrysanthemi) (Recombinant)

Contraindications

• Serious hypersensitivity reactions to asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, including anaphylaxis.

• Serious pancreatitis during previous asparaginase therapy.

• Serious thrombosis during previous asparaginase therapy.

• Serious hemorrhagic events during previous asparaginase therapy.

• Severe hepatic impairment.

Warnings/Precautions

Hypersensitivity Reactions

Severe allergic reactions and potentially life-threatening anaphylaxis reported. Most common reaction observed was rash; a single patient experienced a severe rash. Other hypersensitivity reactions observed with asparaginase products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, hypotension, bronchospasm, dyspnea, and pruritus.

Premedicate with acetaminophen, an H₁-receptor blocker, and an H₂-receptor blocker 30-60 minutes before administration. Administer in a setting with resuscitation equipment and other necessary modalities to treat anaphylaxis, including epinephrine, oxygen, IV steroids, and antihistamines. Discontinue the drug if a severe hypersensitivity reaction occurs.

Pancreatitis

Risk of pancreatitis, including increased amylase or lipase. Hemorrhagic or necrotizing pancreatitis has been reported with use of asparaginase products.

If symptoms suggestive of pancreatitis occur, evaluate patient to establish a diagnosis. Determine serum amylase and lipase levels in patients with signs or symptoms of pancreatitis. In patients with severe or hemorrhagic pancreatitis, discontinue drug. In patients with mild pancreatitis, withhold therapy until signs and symptoms subside and amylase and/or lipase concentrations return to 1.5 times the ULN; may resume the drug after resolution.

Thrombosis

Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, reported.

If a thrombotic event occurs, discontinue drug and initiate appropriate antithrombotic therapy. Consider resuming therapy only if thrombosis was uncomplicated.

Hemorrhage

Bleeding, including serious bleeding events, reported. Bruising and nose bleeds were most common.

In patients treated with asparaginase products, hemorrhage may be associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia. Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy.

Hepatotoxicity, including Hepatic Veno-Occlusive Disease

Elevated bilirubin and/or transaminases reported. Severe, life-threatening hepatotoxicity and potentially fatal cases of hepatic veno-occlusive disease reported as well, including during the induction phase of multiphase chemotherapy. Do not administer to patients with severe hepatic impairment.

Inform patients of signs and symptoms of hepatotoxicity. Monitor bilirubin and transaminase levels prior to each cycle of the drug and at least weekly during cycles of treatment that include the drug, through 4 weeks after final dose. Monitor frequently for signs and symptoms of veno-occlusive disease including rapid weight gain, fluid retention with ascites, hepatomegaly, and rapid bilirubin increases. If a patient develops abnormal liver tests after therapy, monitor for liver test abnormalities and clinical signs and symptoms of veno-occlusive disease more frequently. If serious liver toxicity occurs, discontinue drug and provide supportive care.

Immunogenicity

Anti-drug antibodies reported in a clinical study. The effects of anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn not established.

Specific Populations

Pregnancy

May cause fetal harm based on animal findings.

Confirm pregnancy status prior to initiating therapy.

Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Lactation

Not known whether asparaginase (Erwinia chrysanthemi) (recombinant)-rywn distributes into human milk or has any effects on milk production or on the nursing infant.

Women should not breastfeed during therapy and for 1 week after the final dose.

Females and Males of Reproductive Potential

Prior to initiating therapy, pregnancy testing is recommended in females of childbearing potential. Such women should use effective non-hormonal contraception while receiving the drug and for 3 months after the last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients <1 month of age.

Geriatric Use

Safety and efficacy not established in geriatric patients.

Hepatic Impairment

Effect of hepatic impairment on asparaginase (Erwinia chrysanthemi) (recombinant)-rywn not studied.

Renal Impairment

Effect of renal impairment on asparaginase (Erwinia chrysanthemi) (recombinant)-rywn not studied.

Common Adverse Effects

Most common adverse reactions (>20%) include abnormal liver test results, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, hypokalemia.

Asparaginase (Erwinia chrysanthemi) (Recombinant) Pharmacokinetics

Pharmacokinetic parameters of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn are based on serum asparaginase activity (SAA) following administration of the approved recommended dosage. Age, weight, and sex after dose adjustment for body surface area (BSA), had no significant influence on pharmacokinetics of the drug.

Absorption

Bioavailability

Mean absolute bioavailability following IM administration is 37%.

Plasma Concentrations

Maximum SAA and SAA AUC increase proportionally over a dose range of 12.5–50 mg/m².

Peak plasma concentrations are achieved in a median time of 12 hours.

Distribution

Extent

Not known whether asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is distributed into human milk.

Elimination

Metabolism

Expected to be metabolized into small peptides by catabolic pathways.

Half-life

Apparent half-life is 15.9 hours following IM administration.

Stability

Storage

Parenteral

Injection, for IM Use

Unopened vials: 2–8°C; store in original carton to protect from light.

Prepared syringes: If not used immediately, may store syringe at room temperature (15–25°C) for up to 8 hours or in refrigerator at 2–8°C for up to 24 hours. Prepared syringe does not need to be protected from light during storage.

Actions

• Biosynthetic (recombinant DNA origin) preparation of an asparagine-specific bacterial enzyme. Produced in a Pseudomonas fluorescens expression system genetically altered with the DNA that encodes for asparaginase Erwinia chrysanthemi.

• 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.

Advice to Patients

• Inform patients of the risk of allergic reactions, including anaphylaxis. Instruct the patient on the symptoms of allergic reactions and to seek medical advice immediately if they experience such symptoms.

• Instruct patients on signs and symptoms of pancreatitis and to seek medical attention if they experience severe abdominal pain.

• Instruct patients on the risk of thrombosis and to seek medical advice immediately if they experience headache, arm or leg swelling, shortness of breath, and chest pain.

• Advise patients to report any unusual bleeding or bruising to their healthcare provider.

• Inform patients that liver problems, including severe, life-threatening, or fatal issues and liver test abnormalities may occur during therapy. Advise patients to report any jaundice, severe nausea or vomiting, or easy bleeding or bruising to their healthcare provider.

• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and for 3 months after the last dose.

• Advise women not to breastfeed during treatment with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and for 1 week after the last dose.

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, vitamins, and herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

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) (recombinant)-rywn is available through a specialty pharmacy network. Contact manufacturer or consult the asparaginase (Erwinia chrysanthemi) (recombinant)-rywn website ([Web]) for specific availability information.

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