Asparaginase erwinia chrysanthemi (recombinant)-rywn

asparaginase erwinia chrysanthemi (recombinant)-rywn model

What is Asparaginase erwinia chrysanthemi-rywn?

• Asparaginase erwinia chrysanthemi-rywn (Rylaze) is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen used to treat acute lymphoblastic leukemia and lymphoblastic lymphoma in patients who are allergic to E. coli-derived asparaginase products, as a component of a chemotherapy regimen.

What are the uses of this medicine?

• Asparaginase erwinia chrysanthemi-rywn (Rylaze) is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.

How does this medicine work?

• Asparaginase erwinia chrysanthemi (recombinant)-rywn is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia.
• The pharmacological effect of RYLAZE is based on the killing of leukemic cells due to depletion of plasma asparagine.
• Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival.

Who Should Not Use this medicine?

This medicine cannot be used in patients with:

• Serious hypersensitivity reactions to Erwinia asparaginase, including anaphylaxis.
• Serious pancreatitis during previous asparaginase therapy.
• Serious thrombosis during previous asparaginase therapy.
• Serious hemorrhagic events during previous asparaginase therapy.

Is this medicine FDA approved?

• Asparaginase erwinia chrysanthemi-rywn is FDA approved in the year of 2021.

How should this medicine be used?

Recommended Dosage

• When replacing a long-acting asparaginase product, the recommended dosage of RYLAZE is 25 mg/m² administered intramuscularly every 48 hours.

Recommended Monitoring and Dosage Modifications for Adverse Reactions

• Monitor patient’s bilirubin, transaminases, glucose, and clinical examinations prior to treatment every 2-3 weeks and as indicated clinically.
• If results are abnormal, monitor patients until recovery from the cycle of therapy. If an adverse reaction occurs, modify treatment according to Table

1.

Table 1: Dosage Modifications

Adverse Reaction	Severity*	Action
Hypersensitivity Reaction	Grade 2	• Treat the symptoms.
	Grade 3 to 4	• Discontinue RYLAZE permanently.
Pancreatitis	Grade 2 to 4	• Hold RYLAZE for elevations in lipase or amylase > 2 times the ULN, or for symptomatic pancreatitis. • Resume treatment when lipase and amylase are < 1.5 times the ULN and symptoms are resolved. • Discontinue RYLAZE permanently if clinical necrotizing or hemorrhagic pancreatitis is confirmed.
Thrombosis	Uncomplicated thrombosis	• Hold RYLAZE. • Treat with appropriate antithrombotic therapy. • Upon resolution of symptoms, consider resuming RYLAZE, while continuing antithrombotic therapy.
	Severe or life-threatening thrombosis	• Discontinue RYLAZE permanently. • Treat with appropriate antithrombotic therapy.
Hemorrhage	Grade 3 to 4	• Hold RYLAZE. • Evaluate for coagulopathy and consider clotting factor replacement as needed. • Resume RYLAZE with the next scheduled dose if bleeding is controlled.
Hepatotoxicity	Total bilirubin > 3 times to ≤ 10 times the ULN	• Hold RYLAZE until total bilirubin levels decrease to ≤ 1.5 times the ULN.
	Total bilirubin > 10 times the ULN	• Discontinue RYLAZE and do not make up missed doses.

* Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Preparation and Administration Instructions

• Ensure that medical support is available to appropriately manage anaphylactic reactions when administering RYLAZE
• Visually inspect parenteral drug products for particulate matter, cloudiness, or discoloration prior to administration. If any of these are present, discard the vial. RYLAZE does not contain a preservative.
• Use aseptic technique.
• Administer RYLAZE by intramuscular injection within 4 hours after drawing the dose into the syringe(s).
• Rotate injection sites.
• Do not inject RYLAZE into scar tissue or areas that are reddened, inflamed, or swollen.
• If needed, store the syringe(s) at room temperature (15°C to 25°C [59°F to 77°F]) or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 4 hours. The syringe does not need to be protected from light during storage.

What side effects can this medication cause?

The following clinically significant adverse reactions are described in greater detail in other sections of the labeling:

• Hypersensitivity Reactions
• Pancreatic Toxicity
• Thrombosis
• Hemorrhage
• Hepatotoxicity

What special precautions should I follow?

• Hypersensitivity reactions observed with L-asparaginase class products include angioedema, urticaria, lip swelling, eye swelling, rash or erythema, blood pressure decreased, bronchospasm, dyspnea, and pruritus. Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction.
• Pancreatitis was reported in 14% of patients in clinical trials of RYLAZE. Monitor for symptoms. Discontinue if pancreatitis occurs.
• Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported following treatment with L-asparaginase class products. Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated.
• Bleeding was reported in 17% of patients treated with RYLAZE. Discontinue RYLAZE for severe or life-threatening hemorrhage.
• Elevated bilirubin and/or transaminases occurred in 62% of patients treated with RYLAZE. Discontinue RYLAZE for grade 4 increases of bilirubin.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on findings from animal reproduction studies, RYLAZE can cause fetal harm when administered to a pregnant woman.
• There are no available data on RYLAZE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• Pediatric patient one month and older can use this drug.

What should I know about storage and disposal of this medication?

• Store RYLAZE vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze.