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. Structurally similar to native asparaginase Erwinia chrysanthemi.

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.

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)-rywn Dosage and Administration

General

Pretreatment Screening

• Pregnancy testing recommended prior to initiating therapy 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.

Dispensing and Administration Precautions

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

IM Administration

Administer by IM injection.

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.

Administer IM injection within 4 hours of preparing syringe. 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. The prepared syringe does not need to be protected from light during storage.

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. Refer to the prescribing information for the long-acting asparaginase product for duration of administration.

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. Refer to the prescribing information for the long-acting asparaginase product for duration of administration.

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).

Special Populations

Dosage in Hepatic Impairment

No specific dosage recommendations.

Dosage in Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

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

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.

Warnings/Precautions

Hypersensitivity Reactions

Severe allergic reactions and potentially life-threatening anaphylaxis reported. Most common reaction observed was rash; however, no 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.

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. 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 with asparaginase products.

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

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

Elevated bilirubin and/or transaminases reported.

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

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.

Immunogenicity

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

Specific Populations

Pregnancy

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

Confirm pregnancy status prior to initiating therapy.

Avoid pregnancy during therapy. (See Females and Males of Reproductive Potential under Cautions.) 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.

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.

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. 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 10 hours.

Distribution

Extent

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

Elimination

Metabolism

Expected to be metabolized into small peptides by catabolic pathways.

Half-life

Apparent half-life is 18.2 hours following IM administration.

Stability

Storage

Parenteral

Injection, for IM Use

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

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. Discard any unused portion.

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.

• 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. (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. Contact manufacturer or consult the asparaginase (Erwinia chrysanthemi) (recombinant)-rywn website ([Web]) for specific availability information.

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