L-Asgen 10,000 IU

Acute lymphoblastic leukaemia in adult & paed patients from birth to 18 yr, as part of antineoplastic combination therapy.

IV infusion Infuse over 0.5-2 hr. Adult & childn >1 yr 5,000 u/m² every 3rd day. Childn 6-12 mth 7,500 u/m², <6 mth 6,700 u/m².

Hypersensitivity to asparaginase or any native (non-pegylated) E. coli-asparaginase prep. History of, or existing pancreatitis, serious haemorrhage or thrombosis w/ prior asparaginase therapy. Pre-existing known coagulopathy (eg, haemophilia). Severe hepatic impairment (bilirubin >3x ULN; transaminases >10x ULN).

Discontinue treatment if allergic symptoms occur; in patients developing acute pancreatitis. Interrupt treatment if patients develop severe hepatic impairment (bilirubin >3x ULN, transaminases >10x ULN), severe hypertriglyceridaemia, hyperglycaemia or coagulation disorder (eg, sinus vein thrombosis, severe bleeding). Consider switching to different asparaginase prep in case of low asparaginase activity levels accompanied by appearance of anti-asparaginase Abs. Not to be administered as bolus IV inj; in patients w/ severe hypertriglyceridaemia. Coagulation disorders manifesting either as thrombosis, disseminated intravascular coagulation (DIC), or bleeding. Hyperglycaemia; hyperuricaemia; hypoalbuminaemia; hyperammonaemia. Philadelphia chromosome-+ve patients. Monitor bilirubin, hepatic transaminases, blood/urinary glucose, coagulation parameters (eg, partial thromboplastin time, prothrombin time, antithrombin III, fibrinogen & D-dimer), amylase, lipase, triglycerides & cholesterol; liver parameters before & during treatment. Regularly monitor serum & urine glucose levels; serum protein level. Measure asparaginase activity level in serum or plasma 3 days after last administration, ie, usually directly before next dose is given. Determine plasma ammonia levels in patients w/ unexplained neurologic symptoms or severe & prolonged vomiting. Initiate therapeutic & pharmacological measures that rapidly reduce plasma ammonia levels (eg, protein restriction & haemodialysis), reverse catabolic states & increase removal of nitrogen wastes in case of hyperammonaemia w/ severe clinical symptoms. Aggressive urine alkalinisation & allopurinol use can prevent urate nephropathy. Discontinue use or reduce dose of concomitantly administered immunosuppressive medicinal products if reversible posterior leukoencephalopathy syndrome occurs. Co-administration w/ corticosteroids; other antineoplastic products. Moderate influence on ability to drive & use machines. Not be used in patients w/ severe hepatic impairment. Women of childbearing potential should use effective contraception while being treated & for 7 mth following treatment completion. Men should use effective contraceptive measures & should not father a child while receiving treatment & for 4 mth following treatment completion. Pregnancy. Discontinue treatment during breast-feeding. Higher risk of thrombosis w/ concomitant use of prednisone in childn w/ genetic prothrombotic risk factor (factor V G1691A-mutations, prothrombin G20210A-variation, methylenetetrahydrofolate reductase [MTHFR] T677T-genotype, increased lipoprotein A, hyperhomocysteinaemia). Elderly >65 yr.

Hypersensitivity including flushing, rash, hypotension, oedema/angioedema, urticaria, dyspnoea; hyperglycaemia, hypoalbuminaemia; diarrhoea, nausea, vomiting, abdominal pain; oedema, fatigue; increased transaminases, blood bilirubin, alkaline phosphatase, cholesterol, triglyceride, urea & LDH, VLDL, lipoprotein lipase activity, ammonia, decreased antithrombin III, blood fibrinogen & cholesterol, LDL, total protein. DIC, anaemia, leukopenia, thrombocytopenia; bronchospasm; hypoglycaemia, decreased appetite, wt loss; depression, hallucination, confusion; neurological signs & symptoms including agitation, dizziness & somnolence; thrombosis especially cavernous sinus thrombosis or DVT, haemorrhage; acute pancreatitis; pain (back & joint); increased amylase, lipase, abnormal EEG (reduced α-wave activity, increased theta & delta wave activity).

Concomitant use w/ other medicinal products metabolized by liver; myelosuppressive medicinal products & those known to cause infections. Additive toxicity w/ vincristine. May increase risk of coagulation parameter changes w/ glucocorticoids &/or anticoagulants (eg, coumarin, heparin, dipyridamole, ASA or NSAIDs). Attenuated cytotoxic effect of MTX. Enhanced antitumour & reduced GI & haematological effects of MTX when administered 24 hr following MTX. Reduced efficacy of high-dose cytarabine w/ prior asparaginase dose. Synergistic effect when given following cytarabine. Increased risk of serious infection w/ live vaccines.

Cytotoxic Chemotherapy

L01XX02 - asparaginase ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.

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