ONCASPAR is contraindicated in patients with a: History of serious hypersensitivity reactions, including anaphylaxis, to ONCASPAR or to any of the excipients [see Warnings and Precautions (5.1) ] . History of serious thrombosis with prior L-asparaginase therapy [see Warnings and Precautions (5.2) ] . History of pancreatitis, including pancreatitis related to prior L-asparaginase therapy [see Warnings and Precautions (5.3) ] . History of serious hemorrhagic events with prior L-asparaginase therapy [see Warnings and Precautions (5.5) ] . Severe hepatic impairment [see Warnings and Precautions (5.6) ] . History of serious hypersensitivity reactions to ONCASPAR. ( 4 ) History of serious thrombosis with prior L-asparaginase therapy. ( 4 ) History of pancreatitis with prior L-asparaginase therapy. ( 4 ) History of serious hemorrhagic events with prior L-asparaginase therapy. ( 4 ) Severe hepatic impairment. ( 4 )
AND PRECAUTIONS Anaphylaxis or serious hypersensitivity reactions : Observe patients for 1 hour after administration. Discontinue ONCASPAR in patients with serious hypersensitivity reactions. ( 5.1 ) Thrombosis : Discontinue ONCASPAR in patients with serious thrombotic events. ( 5.2 ) Pancreatitis : Evaluate patients with abdominal pain for pancreatitis. Discontinue ONCASPAR in patients with pancreatitis. ( 5.3 ) Glucose intolerance : Monitor serum glucose. ( 5.4 ) Hemorrhage : Discontinue ONCASPAR for severe or life-threatening hemorrhage. Evaluate for etiology and treat. ( 5.5 ) Hepatotoxicity, including hepatic veno-occlusive disease (VOD) : Monitor for toxicity through recovery from cycle. Discontinue ONCASPAR for severe liver toxicity. ( 5.6 )
5.1 Anaphylaxis and Serious Hypersensitivity Reactions Anaphylaxis and serious hypersensitivity reactions can occur in patients receiving ONCASPAR. The risk of serious hypersensitivity reactions is higher in patients with known hypersensitivity to ( E.) coli derived L-asparaginase formulations. Other hypersensitivity reactions can include angioedema, lip swelling, eye swelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus, and rash <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Premedicate patients 30-60 minutes prior to administration of ONCASPAR. <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span> . Observe patients for 1 hour after administration of ONCASPAR in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (for example, epinephrine, oxygen, intravenous steroids, antihistamines) <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . Discontinue ONCASPAR in patients with serious hypersensitivity reactions.
5.2 Thrombosis Serious thrombotic events, including sagittal sinus thrombosis can occur in patients receiving ONCASPAR <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Discontinue ONCASPAR in patients with serious thrombotic events <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .
5.3 Pancreatitis Pancreatitis can occur in patients receiving ONCASPAR. Hemorrhagic or necrotizing pancreatitis with fatal outcomes have been reported <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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. Discontinue ONCASPAR in patients where pancreatitis is suspected. If pancreatitis is confirmed, do not resume ONCASPAR <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .
5.4 Glucose Intolerance Glucose intolerance can occur in patients receiving ONCASPAR <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In some cases, glucose intolerance is irreversible. Monitor serum glucose <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .
5.5 Hemorrhage Increased prothrombin time, increased partial thromboplastin time, and hypofibrinogenemia can occur in patients receiving ONCASPAR <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Evaluate patients with signs and symptoms of hemorrhage with coagulation parameters including PT, PTT, fibrinogen. Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy. Discontinue ONCASPAR for severe or life-threatening hemorrhage <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .
5.6 Hepatotoxicity, Including Hepatic Veno-Occlusive Disease Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of hepatic veno-occlusive disease (VOD), have been observed in patients treated with ONCASPAR in combination with standard chemotherapy, including during the induction phase of multiphase chemotherapy <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span>. Do not administer ONCASPAR to patients with severe hepatic impairment <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . Evaluate bilirubin and transaminases prior to each dose of ONCASPAR and at least weekly, during cycles of treatment that include ONCASPAR, through 6 weeks after the last dose of ONCASPAR. Monitor frequently for signs and symptoms of hepatic VOD, which may include rapid weight gain, fluid retention with ascites, hepatomegaly (which may be painful), and rapid increase of bilirubin. For patients who develop abnormal liver tests after ONCASPAR, more frequent monitoring for liver test abnormalities and clinical signs and symptoms of VOD is recommended. In the event of serious liver toxicity, including VOD, discontinue treatment with ONCASPAR and provide supportive care <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .