Rylaze

RYLAZE- asparaginase injection
Jazz Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

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.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

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

See the full prescribing information for the long-acting asparaginase product to determine the duration of administration of RYLAZE as replacement therapy.

2.2 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 [see Warnings and Precautions (5.1)]	Grade 2	• Treat the symptoms.
	Grade 3 to 4	• Discontinue RYLAZE permanently.
Pancreatitis [see Warnings and Precautions (5.2)]	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 [see Warnings and Precautions (5.3)]	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 [see Warnings and Precautions (5.4)]	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 [see Warnings and Precautions (5.5)]	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.

2.3 Preparation and Administration Instructions

Ensure that medical support is available to appropriately manage anaphylactic reactions when administering RYLAZE [see Warnings and Precautions (5.1)].

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.

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Determine the dose, total volume of RYLAZE solution required, and the number of RYLAZE vials needed. More than one vial may be needed for a full dose.

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Withdraw the indicated injection volume of RYLAZE into the syringe for injection.

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Do not shake the vial.

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Limit the volume of RYLAZE at a single injection site to 2 mL.

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If the volume to be administered is greater than 2 mL, divide the doses equally into multiple syringes, one for each injection site.

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Discard the remaining unused RYLAZE in the single-dose vial.

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Administer RYLAZE by intramuscular injection within 4 hours after drawing the dose into the syringe(s).

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Rotate injection sites.

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Do not inject RYLAZE into scar tissue or areas that are reddened, inflamed, or swollen.

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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.

3 DOSAGE FORMS AND STRENGTHS

Injection: 10 mg/0.5 mL clear to opalescent, colorless to slightly yellow solution in a single-dose vial.

4 CONTRAINDICATIONS

RYLAZE is contraindicated in patients with a history of:

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Serious hypersensitivity reactions to Erwinia asparaginase , including anaphylaxis [see Warnings and Precautions (5.1)] ;

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Serious pancreatitis during previous asparaginase therapy [see Warnings and Precautions (5.2)] ;

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Serious thrombosis during previous asparaginase therapy [see Warnings and Precautions (5.3)] ;

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Serious hemorrhagic events during previous asparaginase therapy [see Warnings and Precautions (5.4)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions after the use of RYLAZE occurred in 25% of patients in clinical trials, and it was severe in 2% of patients [see Adverse Reactions (6.1)]. The median time from the first dose of RYLAZE to the onset of the first hypersensitivity event was 27 days (range 1-171 days). The most commonly observed reaction was rash (17%), and no patient experienced a severe rash. The median time from the first dose to the first onset of rash was 33.5 days (range 1-127 days).

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.

Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administer RYLAZE in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see Dosage and Administration (2.3)]. Discontinue RYLAZE in patients with serious hypersensitivity reactions.