Summary of the safety profile The primary toxicity of asparaginase results from immunologic reactions caused by exposure to the bacterial protein. Hypersensitivity reactions range from transient flushing or rash and urticaria to bronchospasm, angioedema and anaphylaxis.
In addition, treatment with asparaginase can result in disturbances in organ systems which exhibit a high level of protein synthesis. Decreased protein synthesis can predominantly lead to liver impairment, acute pancreatitis, decreased insulin production with hyperglycaemia, decreased production of clotting factors (especially fibrinogen and antithrombin III) leading to coagulation disorders (thrombosis, bleeding), and decreased production of lipoproteins resulting in hypertriglyceridaemia.
g. jaundice, hepatic necrosis, hepatic failure (rare). g. transaminases, bilirubin, blood lipids, coagulation parameters). Since Spectrila is usually used in combination therapy with other antineoplastic agents, the demarcation from undesirable effects of other medicinal products is often difficult.
Tabulated list of adverse reactions The following adverse reactions, listed in table 1, have been accumulated from clinical trials with Spectrila in 125 children with newly diagnosed acute lymphoblastic leukaemia as well as post-marketing experience with other E.
coli-derived asparaginase preparations in children and adults. Adverse reactions are ranked under headings of frequency, the most frequent first. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Frequencies in this table are defined using the following convention:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Table 1 System organ class Frequency and adverse reaction Infections and infestations Not known Infections Blood and lymphatic system disorders Common Disseminated intravascular coagulation (DIC), anaemia, leukopenia, thrombocytopenia Immune system disorders Very common Hypersensitivity including flushing, rash, hypotension, oedema/angioedema, urticaria, dyspnoea Common Hypersensitivity including bronchospasm 9 Rare Anaphylactic shock Endocrine disorders Very rare Secondary hypothyroidism, hypoparathyroidism Metabolism and nutrition disorders Very common Hyperglycaemia, hypoalbuminaemia Common Hypoglycaemia, decreased appetite, weight loss Uncommon Hyperuricaemia, hyperammonaemia Rare Diabetic ketoacidosis Psychiatric disorders Common Depression, hallucination, confusion Nervous system disorders Common Neurological signs and symptoms including agitation, dizziness and somnolence Uncommon Headaches Rare Ischaemic stroke, reversible posterior leukoencephalopathy syndrome (RPLS), convulsion, disturbances in consciousness including coma Very rare Tremor Vascular disorders Common Thrombosis especially cavernous sinus thrombosis or deep vein thrombosis, haemorrhage Gastrointestinal disorders Very common Diarrhoea, nausea, vomiting, abdominal pain Common Acute pancreatitis Rare Haemorrhagic pancreatitis, necrotising pancreatitis, parotitis Very rare Pancreatitis with fatal outcome, pancreatic pseudocyst Hepatobiliary disorders Rare Hepatic failure with potentially fatal outcome, hepatic necrosis, cholestasis, jaundice Not known Hepatic steatosis General disorders and administration site conditions Very common Oedema, fatigue Common Pain (back pain, joint pain) 10 Investigations Very common Increase in transaminases, blood bilirubin, blood alkaline phosphatase, blood cholesterol, blood triglyceride, very low density lipoprotein (VLDL), lipoprotein lipase activity, blood urea, ammonia, blood lactate dehydrogenase (LDH), Decrease in antithrombin III, blood fibrinogen, blood cholesterol, low density lipoprotein (LDL), total protein Common Increase in amylase, lipase, abnormal electroencephalogram (EEG) (reduced alpha wave activity, increased theta and delta wave activity) Description of selected adverse reactions Immune system disorders Spectrila can induce antibodies of different immunoglobulin classes (IgG, IgM, IgE).
These antibodies may induce clinical allergic reactions, inactivate the enzymatic activity or accelerate the elimination of asparaginase. Allergic reactions can manifest as flushing, rash, pain (joint pain, back pain and abdominal pain), hypotension, oedema/angioedema, urticaria, dyspnoea, bronchospasm up to anaphylactic shock.
The probability of the occurrence of allergic reactions increases with the number of administered doses; however, in very rare cases reactions can occur at the first dose of asparaginase. Most hypersensitivity reactions to asparaginase are observed during subsequent treatment phases (re-induction treatment, delayed intensification).
5/ALL), the following frequencies of allergic events were observed (table 2). 0%) Any allergic event* within 24 hours after asparaginase infusion during induction treatment 16 (16%) 24 (24%) *Including all allergic reactions within 12 hours after asparaginase infusion and all adverse events with CTCAE terms syncope (fainting), hypotension, rash, […]