Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, a biosynthetic (recombinant DNA origin) preparation of an asparagine-specific bacterial enzyme, is an antineoplastic agent.1 The drug is structurally similar to native asparaginase Erwinia chrysanthemi .1, 11
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is used as a component of combination chemotherapy for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adults and pediatric patients ≥1 month of age who have hypersensitivity to E. coli -derived asparaginase preparations.1 The biologic product has been designated an orphan drug by the FDA for use in the treatment of ALL.2
Efficacy and safety of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn for the treatment of patients with ALL and LBL are based principally on data from an open-label, multicenter clinical trial (Study JZP458-201).1, 4 A total of 225 adults and pediatric patients who developed hypersensitivity to E. coli -derived asparaginase or had silent inactivation were included.1, 4 The median age of patients was 10 years (range 1-25 years); 61% were male, 69% were white, 11% Black/African American, and 4% Asian.1 The majority of patients (83%) experienced a hypersensitivity reaction (grade ≥3) to the pegylated asparaginase formulation, pegaspargase, and 15 patients (7%) reported silent inactivation.1 Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn was determined to be efficacious if a nadir serum asparaginase activity of ≥0.1 units/mL (a level predicted to result in clinical efficacy) was achieved and maintained.1 A treatment course consisted of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn administered at various dosages and routes of administration every Monday, Wednesday, and Friday for a total of 6 doses to replace each dose of pegaspargase.1 Results of the study showed that an asparaginase (Erwinia chrysanthemi) (recombinant)-rywn dosage of 25 mg/m2 administered IM every 48 hours provided the target level of asparaginase activity in 96% of patients.1 A dosage regimen of 25 mg/m2 on Monday and Wednesday mornings and 50 mg/m2 on Friday afternoon provided the target level of asparaginase activity in 91% of patients.1
Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn received fast track and priority review from the FDA to alleviate the burden of a global shortage of asparaginase (Erwinia chrysanthemi) (Erwinaze®).3, 5 The key difference between the 2 products is that the asparaginase in asparaginase (Erwinia chrysanthemi) is derived directly from Erwinia chrysanthemi , whereas the asparaginase in asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is produced in a Pseudomonas fluorescens expression system genetically altered with the DNA that encodes the synthesis of asparaginase Erwinia chrysanthemi .1, 6
Dispensing and Administration Precautions
Administer asparaginase (Erwinia chrysanthemi) (recombinant)-rywn by IM injection.1
Visually inspect the drug solution for particulate matter, cloudiness, or discoloration prior to administration.1 The solution should be clear to opalescent, and colorless to slightly yellow; discard the drug if the solution contains visible particles or is cloudy or discolored.1
Prior to administration, determine the dose, total volume, and number of vials of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn solution required based on the patient's body surface area.1 More than one vial may be required for a full dose.1 Using aseptic technique, withdraw the indicated injection volume of the asparaginase (Erwinia chrysanthemi) (recombinant)-rywn solution into a syringe for injection.1
The manufacturer recommends that no more than 2 mL be administered at any one injection site; IM doses exceeding 2 mL should be divided and administered at separate sites.1 Rotate injection sites regularly.1 Do not inject into scar tissue or areas that are reddened, inflamed, or swollen.1
If not used immediately, prepared syringe(s) may be stored at room temperature (15-25°C) for up to 8 hours or in the refrigerator at 2-8°C for up to 24 hours.1 The syringes do not need to be protected from light during storage.1 Refrigerate intact and unopened asparaginase (Erwinia chrysanthemi) (recombinant)-rywn vials at 2-8°C in their original carton to protect the drug from light.1 Do not shake or freeze the vials.1
Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
For adults and pediatric patients ≥1 month of age who have developed hypersensitivity to E. coli -derived asparaginase, there are 2 dosage regimens that may be utilized to replace the long-acting asparaginase product.1 These regimens include:
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).1 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.1
When Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn Is Administered | Recommended Duration of Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn to Replace Calaspargase Pegol | Recommended Duration of Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn to Replace Pegaspargase |
|---|---|---|
25 mg/m2 IM every 48 hours | Replace one dose of calaspargase pegol products with 11 doses of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn | Replace one dose of pegaspargase products with 7 doses of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn |
25 mg/m2 on Monday and Wednesday mornings and 50 mg/m2 on Friday afternoon | Replace one dose of calaspargase pegol products with 9 doses of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn | Replace one dose of pegaspargase products with 6 doses of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn |
In order to reduce the risk and severity of hypersensitivity reactions associated with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, patients should be premedicated with acetaminophen, an H1-receptor blocker, and an H2-receptor blocker 30-60 minutes before administration.1
Dosage Modification for Toxicity and Contraindications to Continued Therapy
Dosage interruption, reduction, or discontinuance of therapy may be necessary based on severity of adverse reactions (see Table 2).1
Toxicity | Recommendation |
|---|---|
Hypersensitivity reactions | Grade 3 or 4 hypersensitivity reaction: discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy permanently. Grade 2 hypersensitivity reaction: treat symptoms of the reaction. |
Pancreatitis | Grades 2, 3, or 4 pancreatitis: interrupt asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy for symptomatic pancreatitis or when lipase or amylase is >2 times the upper limit of normal (ULN). Resume therapy when lipase and amylase are <1.5 times the ULN and symptoms resolve. Discontinue the drug permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed. |
Thrombosis | Uncomplicated thrombosis: interrupt asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy and initiate appropriate antithrombotic therapy. Once symptoms resolve, consider resuming asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy while continuing antithrombotic therapy. Severe or life-threatening thrombosis: discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy permanently and initiate appropriate antithrombotic therapy. |
Hemorrhage | Grade 3 or 4 hemorrhage: interrupt asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy. Evaluate for coagulopathy and consider clotting factor replacement therapy as needed. Resume asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy with the next scheduled dose if bleeding is controlled. |
Hepatotoxicity | Total bilirubin >10 times the ULN: discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy. Do not make up any missed doses. Total bilirubin >3 times to ≤10 times the ULN: interrupt asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy until total bilirubin levels decrease to ≤1.5 times the ULN. |
The manufacturer makes no specific dosage recommendations for geriatric patients or for patients with renal or hepatic impairment; however, asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is contraindicated in patients with severe hepatic impairment.1
Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn may cause severe allergic reactions and potentially life-threatening anaphylaxis in some patients.1 In clinical studies, 29% of patients who received the drug experienced hypersensitivity reactions.1 Reactions were considered severe in 6% of patients.1 After intramuscular administration, 2% of patients experienced anaphylaxis; discontinuation of therapy due to hypersensitivity reactions occurred in 5% of patients.1 An increased incidence of hypersensitivity reactions was seen when asparaginase (Erwinia chrysanthemi) (recombinant)-rywn was administered IV; however, this is NOT an approved administration route.1
The most commonly observed reaction was rash (19%) and a single patient experienced a severe rash.1 The median number of doses of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn prior to the onset of the first hypersensitivity reaction was 12 doses (range 1-64 doses).1 Other hypersensitivity reactions observed with asparaginase products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, hypotension, bronchospasm, dyspnea, and pruritus.1
Patients should be premedicated with acetaminophen, an H1-receptor blocker, and an H2-receptor blocker 30-60 minutes before administration.1 Administer asparaginase (Erwinia chrysanthemi) (recombinant)-rywn 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
Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn may cause pancreatitis, including increased amylase or lipase.1 In clinical studies of the drug, 20% of patients reported pancreatitis and 8% experienced severe pancreatitis.1 Symptomatic pancreatitis occurred in 7% of patients, and was severe in 6% of patients.1 Elevated amylase or lipase concentrations in patients without symptomatic pancreatitis occurred in 13%.1 Hemorrhagic or necrotizing pancreatitis has been reported with use of asparaginase products.1
Inform patients of the signs and symptoms of pancreatitis, which can be fatal if left untreated.1 If symptoms suggestive of pancreatitis occur, evaluate the patient to establish a diagnosis.1 Determine serum amylase and lipase levels in patients with any signs or symptoms of pancreatitis.1 In patients with severe or hemorrhagic pancreatitis, discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy.1 In cases of mild pancreatitis, withhold therapy until the signs and symptoms subside and amylase and/or lipase concentrations return to 1.5 times the upper limit of normal (ULN); may resume treatment after resolution of mild pancreatitis.1
Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported in 1% of patients treated with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn.1 If a thrombotic event occurs, discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and initiate appropriate antithrombotic therapy.1 Consider resuming treatment with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn only if the thrombosis was uncomplicated.1
In clinical trials, bleeding was reported in 25% of patients treated with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and was severe in 2% of patients.1 The most common bleeding complications observed were bruising (12%) and nose bleeds (9%).1 Hemorrhage may be associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia in patients treated with asparaginase products.1 Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy.1
Hepatotoxicity, including Hepatic Veno-Occlusive Disease
In clinical trials, elevated bilirubin and/or transaminases occurred in 75% of patients treated with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn; 26% of patients had grade 3 or 4 elevations.1 Elevated bilirubin and elevated transaminases were reported in 28% and 73% of patients in clinical trials, respectively.1 Grade 3 or 4 elevations of each of these liver function markers occurred in 2% and 25% of patients, respectively.1
Severe, life-threatening hepatotoxicity and potentially fatal cases of hepatic veno-occlusive disease have been reported with use, including during the induction phase of multiphase chemotherapy.1 Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn should not be administered to patients with severe hepatic impairment.1
Inform patients of the signs and symptoms of hepatotoxicity.1 Monitor bilirubin and transaminase levels prior to each cycle of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and at least weekly during cycles of treatment that include the drug, through 4 weeks after the final dose.1 Patients should be monitored frequently for signs and symptoms of veno-occlusive disease including rapid weight gain, fluid retention with ascites, hepatomegaly, and rapid bilirubin increases.1 If a patient develops abnormal liver tests after asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, clinicians should monitor for liver test abnormalities and clinical signs and symptoms of veno-occlusive disease more frequently.1 If serious liver toxicity occurs, discontinue asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy and provide supportive care.1
In a clinical study, 78 (47%) of 166 patients treated with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn developed anti-drug antibodies.1 The effects of these anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn have not been established.1
There are no available data on the use of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn in pregnant women; however, based on animal findings, the drug may cause fetal harm.1
Avoid pregnancy during asparaginase (Erwinia chrysanthemi) (recombinant)-rywn therapy.1 Apprise patients of the potential hazard to the fetus if the drug is used during pregnancy.1
It is not known whether asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is distributed into human milk or whether the drug has any effects on the nursing infant or on milk production.1 Due to the potential for serious adverse reactions in nursing infants, women should be advised not to breastfeed during treatment with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and for 1 week after the final dose.1
Females and Males of Reproductive Potential
Prior to initiation of therapy, pregnancy testing is recommended in females of childbearing potential.1 Such females should use effective non-hormonal contraception while receiving asparaginase (Erwinia chrysanthemi) (recombinant)-rywn and for 3 months after the last dose.1
The safety and efficacy of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn in the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have been established in pediatric patients ≥1 month of age who developed hypersensitivity to a long-acting E. coli -derived asparaginase product.1 Evidence from a well-controlled study in adults and pediatric patients supports use of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn in this pediatric age group.1 The trial included 139 pediatric patients, including 2 infants (1 month to <2 years), 99 children (2 years to <12 years), and 38 adolescents (12 years to <17 years).1 There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups.1
The safety and efficacy of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn have not been established in pediatric patients <1 month of age.1
Clinical studies of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn did not include a sufficient number of patients ≥65 years of age to determine whether they respond differently than younger patients.1
The effect of hepatic impairment on the pharmacokinetics of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn has not been studied.1
The effect of renal impairment on the pharmacokinetics of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn has not been studied.1
The most common adverse reactions (incidence >20%) reported with asparaginase (Erwinia chrysanthemi) (recombinant)-rywn 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, and hypokalemia.1
Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is a biosynthetic (recombinant DNA origin) preparation of an asparagine-specific bacterial enzyme.1 Asparaginase (Erwinia chrysanthemi) (recombinant)-rywn catalyzes the deamidation of the amino acid L-asparagine to aspartic acid and ammonia, resulting in reduced concentrations of circulating asparagine.1 Because of a lack of asparagine synthetase, some leukemic cells cannot synthesize asparagine and depend on an exogenous source of the amino acid for protein synthesis and cell survival.1, 7, 8 Because normal cells are able to synthesize asparagine, they are less affected by asparaginase-induced depletion of the amino acid.8
Pharmacokinetic parameters of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn are based on serum asparaginase activity (SAA) following administration of the approved recommended dosage.1 Maximum SAA and area under the SAA-time curve (AUC) increase proportionally over a dose range of 12.5-50 mg/m2.1 Peak plasma concentrations of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn are achieved in a median time of 12 hours.1 The drug is expected to be metabolized into small peptides by catabolic pathways.1 Mean absolute bioavailability following IM administration is 37%.1 The apparent half-life of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn is 15.9 hours following IM administration.1 Age, weight, and sex after dose adjustment for body surface area (BSA), had no significant influence on pharmacokinetics of the drug.1
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].
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
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IM use | 10 mg/0.5 mL | Rylaze® | Jazz Pharmaceuticals Inc. |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions April 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Jazz Pharmaceuticals. Rylaze® (asparaginase [Erwinia chrysanthemi] [recombinant]-rywn) injection for intramuscular use prescribing information. 2024 Apr. [Web]
2. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2025 Jan 16. [Web]
3. Food and Drug Administration. FDA News Release: FDA Approves Component of Treatment Regimen for Most Common Childhood Cancer published June 30, 2021. From the FDA website [Web]
4. US National Library of Medicine. Clinicaltrials.gov. An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL). NCT04145531.
5. Wheeler, M. ASHP Current Drug Shortages: Asparaginase Erwinia chrysanthemi. American Society of Health System Pharmacists; Updated June 11, 2024. Accessed January 16, 2025.
6. Jazz Pharmaceuticals. Erwinaze® (asparaginase [Erwinia chrysanthemi]) injection prescribing information. Palo Alto, CA; 2019 Dec.
7. van den Berg H. Asparaginase revisited. Leuk Lymphoma . 2011; 52:168-78. [PubMed 21281233]
8. Lundbeck. Elspar® (asparaginase) injection prescribing information. Deerfield, IL; 2013 July
10. Jazz Pharmaceuticals. Rylaze®. From Rylaze website. Accessed January 16, 2025.
11. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761179Orig1s000: Multi-discipline review. From FDA website. [Web]