Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn (Monograph)

Brand name: Rylaze
Drug class: Antineoplastic Agents
Molecular formula: C₁₅₄₆H₂₅₁₀N₄₃₂O₄₇₆S₉ (monomer)

Medically reviewed by Drugs.com on Feb 7, 2024. Written by ASHP.

Introduction

Antineoplastic agent; biosynthetic (recombinant DNA origin) preparation of an asparagine-specific enzyme.¹ Structurally similar to native asparaginase Erwinia chrysanthemi.^{1 11}

Uses for Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn

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.^{1 2 11}

Received fast track and priority review from the FDA to alleviate the burden of a global shortage of asparaginase (Erwinia chrysanthemi).^{3 5}

Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn Dosage and Administration

General

Pretreatment Screening

• Pregnancy testing recommended prior to initiating therapy in females of reproductive potential.¹

Patient Monitoring

• Monitor bilirubin, transaminases, and glucose concentrations, and perform clinical examinations prior to treatment every 2–3 weeks, and if clinically indicated.¹ If results are abnormal, monitor patients until recovery from the cycle of therapy.¹

Dispensing and Administration Precautions

• Administer the drug in a setting with resuscitation equipment and other agents necessary to treat anaphylactic reactions.¹

IM Administration

Administer by IM injection.¹

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.¹

Do not give >2 mL at one injection site.¹ If IM dose >2 mL, divide the dose and administer at separate sites.¹ Rotate injection sites regularly.¹ Do not inject into scar tissue or areas that are reddened, inflamed, or swollen.¹

Administer IM injection within 4 hours of preparing syringe.¹ If needed, may store the syringe at room temperature (15–25°C) or in the refrigerator at 2–8°C for up to 4 hours.¹ The prepared syringe does not need to be protected from light during storage.¹

Dosage

Pediatric Patients

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

IM

Children ≥1 month of age: recommended dosage when replacing a long-acting asparaginase product is 25 mg/m² administered every 48 hours for the duration of asparaginase activity expected for that product.^{1 11} Refer to the prescribing information for the long-acting asparaginase product for duration of administration.¹

Adults

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

IM

Recommended dosage when replacing a long-acting asparaginase product is 25 mg/m² administered every 48 hours for the duration of asparaginase activity expected for that product.^{1 11} Refer to the prescribing information for the long-acting asparaginase product for duration of administration. ¹

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 1).¹

Special Populations

Dosage in Hepatic Impairment

No specific dosage recommendations.¹

Dosage in Renal Impairment

No specific dosage recommendations.¹

Geriatric Patients

No specific dosage recommendations.¹

Cautions for Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn

Contraindications

• Serious hypersensitivity reactions to asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, including anaphylaxis.¹

• Serious pancreatitis during previous asparaginase therapy.¹

• Serious thrombosis during previous asparaginase therapy.¹

• Serious hemorrhagic events during previous asparaginase therapy.¹

Warnings/Precautions

Hypersensitivity Reactions

Severe allergic reactions and potentially life-threatening anaphylaxis reported.¹ Most common reaction observed was rash; however, no patient experienced a severe rash.¹ Other hypersensitivity reactions observed with asparaginase products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, hypotension, bronchospasm, dyspnea, and pruritus.¹

Administer in a setting with resuscitation equipment and other necessary modalities to treat anaphylaxis, including epinephrine, oxygen, IV steroids, and antihistamines.¹ Discontinue the drug if a severe hypersensitivity reaction occurs.¹

Pancreatitis

Risk of pancreatitis.¹ Hemorrhagic or necrotizing pancreatitis has been reported with use of asparaginase products.¹

If symptoms suggestive of pancreatitis occur, evaluate patient to establish a diagnosis.¹ Determine serum amylase and lipase levels in patients with signs or symptoms of pancreatitis.¹ In patients with severe or hemorrhagic pancreatitis, discontinue drug.¹ 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.¹

Thrombosis

Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, reported with asparaginase products.¹

If a thrombotic event occurs, discontinue drug and initiate appropriate antithrombotic therapy.¹ Consider resuming therapy only if thrombosis was uncomplicated.¹

Hemorrhage

Bleeding, including serious bleeding events, reported.¹ Bruising (e.g., contusion, increased tendency to bruise, injection site bruising) and nose bleeds were most common.¹ Hematuria, disseminated intravascular coagulopathy, rectal bleeding, and gingival bleeding also observed.¹

In patients treated with asparaginase products, hemorrhage may be associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia.¹ Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy.¹

Hepatotoxicity

Elevated bilirubin and/or transaminases reported.¹

Inform patients of signs and symptoms of hepatotoxicity.¹ Monitor bilirubin and transaminase levels prior to treatment every 2–3 weeks and as clinically indicated during treatment.¹ If serious liver toxicity occurs, discontinue drug and provide supportive care.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.¹ Embryofetal mortality and fetal structural abnormalities reported in animal studies at doses lower than maximum recommended human dosage.¹

Immunogenicity

The incidence of anti-drug antibodies and effects on pharmacokinetics, pharmacodynamics, safety, or effectiveness of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn not established.¹

Specific Populations

Pregnancy

May cause fetal harm.¹ Embryofetal mortality and fetal structural abnormalities reported in animal studies.¹

Confirm pregnancy status prior to initiating therapy.¹

Avoid pregnancy during therapy.¹ (See Females and Males of Reproductive Potential under Cautions.) If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹

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.¹

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

Females and Males of Reproductive Potential

Prior to initiating therapy, pregnancy testing is recommended in females of childbearing potential.¹ Such women should use effective non-hormonal contraception while receiving the drug and for 3 months after the last dose.¹

Pediatric Use

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

Geriatric Use

Safety and efficacy not established in geriatric patients.¹

Common Adverse Effects

Most common adverse reactions (>20%) include abnormal liver test results, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia.¹

Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn Pharmacokinetics

Pharmacokinetic parameters of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn are based on serum asparaginase activity (SAA) following administration of the approved recommended dosage.¹ Age, weight, and sex after dose adjustment for body surface area (BSA), had no significant influence on pharmacokinetics of the drug.¹

Absorption

Bioavailability

Mean absolute bioavailability following IM administration is 37%.¹

Plasma Concentrations

Maximum SAA and SAA AUC increase proportionally over a dose range of 12.5–50 mg/m² .¹

Peak plasma concentrations are achieved in a median time of 10 hours.¹

Distribution

Extent

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

Elimination

Metabolism

Expected to be metabolized into small peptides by catabolic pathways.¹

Half-life

Apparent half-life is 18.2 hours following IM administration.¹

Stability

Storage

Parenteral

Injection, for IM Use

Unopened vials: 2–8°C; protect from light.¹

Prepared syringe: Use within 4 hours of preparation; if needed, may store at room temperature (15–25°C) or refrigerated at 2–8°C for up to 4 hours.¹ Discard any unused portion.¹

Actions

• Biosynthetic (recombinant DNA origin) preparation of an asparagine-specific bacterial enzyme.¹ Produced in a Pseudomonas fluorescens expression system genetically altered with the DNA that encodes for asparaginase Erwinia chrysanthemi.¹

• Inactivates the amino acid asparagine, which is required by tumor cells for protein synthesis.^{1 7 8}

• Catalyzes deamidation of asparagine to aspartic acid and ammonia, which reduces circulating concentrations of asparagine and leads to leukemic cell death.^{1 7 8}

Advice to Patients

• Inform patients of the risk of allergic reactions, including anaphylaxis.¹ Instruct the patient on the symptoms of allergic reactions and to seek medical advice immediately if they experience such symptoms.¹

• Instruct patients on signs and symptoms of pancreatitis and to seek medical attention if they experience severe abdominal pain.¹

• 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.¹

• Advise patients to report any unusual bleeding or bruising to their healthcare provider.¹

• Advise patients to report any jaundice, severe nausea or vomiting, or easy bleeding or bruising to their healthcare provider.¹

• Advise pregnant women of the potential risk to a fetus.¹ Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy.¹ 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.¹

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

• 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.¹

• Inform 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) (recombinant)-rywn is available through a specialty pharmacy network.¹⁰ Contact manufacturer or consult the asparaginase (Erwinia chrysanthemi) (recombinant)-rywn website ([Web]) for specific availability information.¹⁰

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