Asparaginase

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. 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.

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.

There are two RYLAZE regimens that can be used to replace a long-acting asparaginase product. The recommended dosages of RYLAZE are: When administered every 48 hours • 25 mg/m 2 intramuscularly every 48 hours, When administered Monday/Wednesday/Friday • 25 mg/m 2 intramuscularly on Monday morning and Wednesday morning and 50 mg/m 2 intramuscularly on Friday afternoon.

RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to Erwinia asparaginase, including anaphylaxis, • History of serious pancreatitis during previous asparaginase therapy, • History of serious thrombosis during previous asparaginase therapy, • History of serious hemorrhagic events during previous asparaginase therapy, • Severe hepatic impairment. RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to RYLAZE, including anaphylaxis. • History of serious pancreatitis during previous L-asparaginase therapy. • History of serious thrombosis during previous L-asparaginase therapy.

• Hypersensitivity: Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction. • Pancreatitis: Monitor for symptoms. Discontinue if pancreatitis occurs. • Thrombosis: Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated. • Hemorrhage: Discontinue RYLAZE for severe or life-threatening hemorrhage. • Hepatotoxicity, including hepatic veno-occlusive disease: Discontinue RYLAZE for grade 4 increases of bilirubin.

The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Hypersensitivity Reactions • Pancreatic Toxicity • Thrombosis • Hemorrhage • Hepatotoxicity, including VOD Most common adverse reactions (incidence > 20%) are abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.

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.