red for up to 4 hours at room temperature (15°C to 25°C [59°F to77°F]) or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours.
•Protect from light. Do not shake or freeze.
3 DOSAGE FORMS AND STRENGTHS
Injection: 3,750 units/5 mL (750 units/mL) clear, colorless solution in a single-dose vial.
4 CONTRAINDICATIONS
ASPARLAS is contraindicated in patients with:
•History of serious hypersensitivity reactions, including anaphylaxis, to pegylatedL-asparaginase therapy [see Warnings and Precautions (5.1)];
•History of serious thrombosis during previous L-asparaginase therapy [see Warnings andPrecautions (5.3)];
•History of serious pancreatitis during previous L-asparaginase therapy [see Warnings andPrecautions (5.2)];
•History of serious hemorrhagic events during previous L-asparaginase therapy [see Warningsand Precautions (5.4)];
•Severe hepatic impairment [see Warnings and Precautions (5.5)].
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity
Grade 3 and 4 hypersensitivity reactions including anaphylaxis have been reported in clinical trialswith ASPARLAS with an incidence between 7 to 21% [see Contraindications (4), Adverse Reactions (6.1)].
Hypersensitivity reactions observed with other asparaginases include angioedema, lip swelling, eyeswelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus and rash.
Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administerASPARLAS in a clinical setting with resuscitation equipment and other agents necessary to treatanaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see Dosage andAdministration (2)] and observe patients for 1 hour after administration. Discontinue ASPARLAS in patientswith serious hypersensitivity reactions.
5.2 Pancreatitis
Cases of pancreatitis have been reported in clinical trials with ASPARLAS with an incidence between12 to 16% [see Adverse Reactions (6.1)]. Hemorrhagic or necrotizing pancreatitis have been reported withother asparaginases.
Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal.
Assess serum amylase and/or lipase levels to confirm early signs of pancreatic inflammation. DiscontinueASPARLAS if pancreatitis is suspected; if pancreatitis is confirmed, do not resume ASPARLAS [seeDosage and Administration (2.2)].
5.3 Thrombosis
Serious thrombotic events, including sagittal sinus thrombosis, have been reported in clinical trialswith ASPARLAS with an incidence of 9 to 12%. Discontinue ASPARLAS in patients experiencing seriousthrombotic events [see Dosage and Administration (2.2), Adverse Reactions (6.1)].
5.4 Hemorrhage
Hemorrhage associated with increased prothrombin time (PT), increased partial thromboplastin time(PTT), and hypofibrinogenemia have been reported in patients receiving ASPARLAS [see AdverseReactions (6.1)]. eva luate patients with signs and symptoms of hemorrhage with coagulation parametersincluding PT, PTT, fibrinogen. Consider appropriate replacement therapy in patients with severe orsymptomatic coagulopathy [see Dosage and Administration (2.2)].
5.5 Hepatotoxicity
Hepatotoxicity and abnormal liver function, including elevations of transaminase, bilirubin (direct andindirect), reduced serum albumin, and |
