Asparaginase Erwinia Chrysanthemi (recombinant)-rywn

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. 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. ( 1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Pancreatic Toxicity [see Warnings and Precautions ( 5.2 )] • Thrombosis [see Warnings and Precautions ( 5.3 )] • Hemorrhage [see Warnings and Precautions ( 5.4 )] • Hepatotoxicity, including VOD [see Warnings and Precautions ( 5.5 )] 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.

8.1 Pregnancy Risk Summary 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.

5 WARNINGS AND PRECAUTIONS • Hypersensitivity: Monitor for signs or symptoms. Discontinue RYLAZE for serious reaction. ( 5.1 ) • Pancreatitis: Monitor for symptoms. Discontinue if pancreatitis occurs. ( 5.2 ) • Thrombosis: Discontinue RYLAZE for severe or life-threatening thrombosis. Provide anticoagulation therapy as indicated. ( 5.3 ) • Hemorrhage: Discontinue RYLAZE for severe or life-threatening hemorrhage. ( 5.4 ) • Hepatotoxicity, including hepatic veno-occlusive disease: Discontinue RYLAZE for grade 4 increases of bilirubin. ( 5.5 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions after the use of RYLAZE occurred in 29% of patients in clinical trials, and it was severe in 6% of patients [see Adverse Reactions ( 6.1 )] . 4 CONTRAINDICATIONS RYLAZE is contraindicated in patients with: • History of serious hypersensitivity reactions to Erwinia asparaginase , including anaphylaxis [see Warnings and Precautions ( 5.1 )] ; • History of serious pancreatitis during previous asparaginase therapy [see Warnings and Precautions ( 5.2 )] ; • History of serious thrombosis during previous asparaginase therapy [see Warnings and...