Rylaze

What is Rylaze?

Rylaze Model

Rylaze, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) or

lymphoblastic lymphoma (LBL) in pediatric and adult patients one month and older who have developed hypersensitivity to the drug.

What are the uses of this medicine?

RYLAZE is an asparagine specific enzyme 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?

The drug is an asparaginase—an enzyme that fights cancer cells by starving them of the nutrients they need to survive.

Who Should Not Use this medicine?

Pregnant women are not advised to use this medicine in case of fetal harm.

Is this medicine FDA approved?

Rylaze has been FDA approved since June 30, 2021.

How should this medicine be used?

It should be injected into a muscle, which will be performed by your oncologist.

What are the  dosage forms and brand names of this medicine?

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

What side effects can this medication cause?

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• easy bruising or bleeding (nosebleeds, bleeding gums)
• any bleeding that will not stop
• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing
• signs of liver or pancreas problems--severe stomach pain (that may spread to your back), nausea or vomiting, jaundice (yellowing of the skin or eyes)
• signs of a blood clot--sudden numbness or weakness (especially on one side of the body), severe headache, chest pain, feeling short of breath, pain or swelling in an arm or leg
• low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough
• high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor

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. 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). Discontinue RYLAZE in patients with serious hypersensitivity reactions.

Pancreatitis

Pancreatitis was reported in 14% of patients in clinical trials of RYLAZE and was severe in 6%. Clinical pancreatitis occurred in 5% of patients, and it was severe in 4% of patients. Elevated amylase or lipase without clinical diagnosis of pancreatitis was observed in 9% of patients, and it was severe in 2% of patients treated with RYLAZE. Hemorrhagic or necrotizing pancreatitis have been reported with L-asparaginase class products.

Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal. Evaluate patients with symptoms compatible with pancreatitis to establish a diagnosis. Assess serum amylase and lipase levels in patients with any signs or symptoms of pancreatitis. Discontinue RYLAZE in patients with severe or hemorrhagic pancreatitis. In the case of mild pancreatitis, withhold RYLAZE until the signs and symptoms subside and amylase and/or lipase levels return to 1.5 times the ULN . After resolution of mild pancreatitis, treatment with RYLAZE may be resumed.

Thrombosis

Serious thrombotic events, including sagittal sinus thrombosis and pulmonary embolism, have been reported following treatment with L-asparaginase class products. Discontinue RYLAZE for a thrombotic event, and administer appropriate antithrombotic therapy. Consider resumption of treatment with RYLAZE only if the patient had an uncomplicated thrombosis.

Hemorrhage

Bleeding was reported in 17% of patients treated with RYLAZE, and it was severe in 1%. Most commonly observed reactions were bruising (8%) (contusion, increased tendency to bruise and injection site bruising) and nose bleeding (6%), which was severe in 1% of patients. Other observed bleeding reactions included hematuria (2%), disseminated intravascular coagulopathy (1%), rectal bleeding (1%) and gingival bleeding (1%).

In patients treated with L-asparaginase class 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 occurred in 62% of patients treated with RYLAZE in clinical trials, and 12% had Grade ≥ 3 elevations.
• Inform patients of the signs and symptoms of hepatotoxicity.
• Evaluate bilirubin and transaminases prior to treatment every 2-3 weeks and as indicated clinically during treatment with RYLAZE.
• In the event of serious liver toxicity, discontinue treatment with RYLAZE and provide supportive care.

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.

• In animal reproductive and developmental toxicity studies, intramuscular administration of asparaginase Erwinia chrysanthemi to pregnant rats and rabbits during organogenesis resulted in structural abnormalities and embryo-fetal mortality at exposures below those in patients at the recommended human dose.
• Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.

Can this medicine be used in children?

• The safety and effectiveness of RYLAZE in the treatment of ALL and LBL have been established in pediatric patients 1 month to < 17 years who have developed hypersensitivity to a long-acting E. coli-derived asparaginase.
• Use of RYLAZE in these age groups is supported by evidence from an adequate and well-controlled study in adults and pediatric patients.
• The trial included 84 pediatric patients, including 2 infants (1 month to < 2 years), 62 children (2 years to < 12 years old), and 20 adolescents (12 years to < 17 years old).
• There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups.
• The safety and effectiveness of RYLAZE have not been established in pediatric patients younger than 1 month of age.

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

• RYLAZE injection is supplied as a sterile, clear to opalescent, colorless to slightly yellow, preservative-free solution in single-dose vials.
• Each single-dose vial (NDC 68727-900-01) contains 10 mg/0.5 mL asparaginase erwinia chrysanthemi (recombinant)-rywn.
• Each carton of RYLAZE (NDC 68727-900-03) contains 3 single-dose vials.
• 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.

References

• Dailymed label info on Rylaze
• FDA Rylaze

Rylaze Resources
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