ONCASPAR

Oncaspar should be prescribed and administered by physicians and/or health care personnel experienced in the use of antineoplastic products. It should only be given in a hospital setting where appropriate resuscitation equipment is available.

4). 5). g. g. 4). 3 ml Oncaspar)/m2 body surface area every 14 days. 1 ml Oncaspar)/kg body weight every 14 days. 67 ml Oncaspar)/m2 body surface area every 14 days. Treatment may be monitored based on the trough serum asparaginase activity measured before the next administration of pegaspargase.

4). Special populations Renal impairment As pegaspargase is a protein with a high molecular weight, it is not excreted renally, and no dose adjustment is necessary in patients with renal impairment. Hepatic impairment No dose adjustment is necessary in patients with hepatic impairment.

Elderly There are limited data available for patients older than 65 years. Method of administration Oncaspar can be given by intramuscular (IM) injection or intravenous (IV) infusion. For smaller volumes, the preferred route of administration is intramuscular.

When Oncaspar is given by intramuscular injection the volume injected at one site should not exceed 2 ml in children and adolescents, and 3 ml in adults. If a higher volume is given, the dose should be divided and given at several injection sites.

9%) solution for injection or 5% glucose solution. The diluted solution can be given together with an already-running infusion of either sodium chloride 9 mg/ml or 5% glucose. Do not infuse other medicinal products through the same intravenous line during administration of Oncaspar.

6.

Summary of the safety profile The adverse reactions described in this section are derived from clinical studies data and post-marketing experience of Oncaspar in ALL patients. The safety profile is based on randomised, controlled, prospective, open-label multicentre studies using Oncaspar at a dose of 2500 U/m2 administered intravenously as a comparative treatment (studies DFCI 11-001 and AALL07P4).

1 for CCG-1962 and CCG-1991). The most common adverse reactions with Oncaspar (observed in at least 2 studies with a frequency of >10%) included: alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, activated partial thromboplastin time prolonged, hypertriglyceridaemia, hyperglycaemia, and febrile neutropenia.

The most common, severe adverse reactions with Oncaspar (graded 3 or 4) observed in studies DFCI 11-001 and AALL07P4 with a frequency of >5% included: alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, febrile neutropenia, hyperglycaemia, lipase increased, and pancreatitis.

Tabulated list of adverse reactions Adverse reactions and their frequencies are reported in Table 1. Frequencies are defined by 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) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 5) Renal and urinary disorders Not known: Renal failure acute* General disorders and administration site conditions Not known: Pyrexia *Adverse reactions observed with other asparaginases in the class **Cases of pulmonary embolism, venous thrombosis, venous thrombosis limb, and thrombophlebitis superficial were observed in DFCI 11-001 ***Legend: CNS thrombosis **** Cases of antithrombin III and neutrophil count decreased were observed in CL2- 95014-002 and CL2-95014-003 studies Description of selected adverse reactions The following adverse reactions have been observed in association with asparaginase therapy.

Although they have not been specifically associated with the use of pegaspargase, they may occur with the use of Oncaspar: Blood and lymphatic system disorders Oncaspar can cause mild to moderate myelosuppression, and all three blood cell lines can be affected.

, stroke, seizure, headache or loss of consciousness. Nervous system disorders Oncaspar may cause central nervous system dysfunctions manifesting as convulsions, and less frequently confusional state and somnolence (mildly impaired consciousness).

In rare cases, a reversible posterior leukoencephalopathy syndrome (RPLS) may occur. In very rare cases, mild tremor in the fingers has been described. Gastrointestinal disorders About half of patients develop mild to moderate gastrointestinal reactions such as loss of appetite, nausea, vomiting, abdominal cramps, diarrhoea and weight loss.

Acute pancreatitis can occur commonly. There have been isolated reports of formation of pseudocysts (up to four months after the last treatment). Haemorrhagic or necrotising pancreatitis occurs rarely. One case of pancreatitis with simultaneous acute parotitis has been described with L-asparaginase treatment.

In single cases, haemorrhagic or necrotising pancreatitis with fatal outcome has been reported. Serum amylase can rise during and also after the conclusion of Oncaspar therapy. Renal and urinary disorders Acute renal failure may develop in rare cases during treatment with L- asparaginase-containing regimens.

Very common:

Weight decreased, hypoalbuminaemia, alanine aminotransferase increased, aspartate aminotransferase increased, hypertriglyceridaemia, blood fibrinogen decreased, lipase increased, amylase increased, activated partial thromboplastin time […]

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Asparaginase antibodies The presence of anti-asparaginase antibodies may be associated with low asparaginase activity levels due to potential neutralising activity of these antibodies.

In such cases, a switch to a different asparaginase preparation should be considered. Measurement of the asparaginase activity level in serum or plasma may be undertaken in order to rule out an accelerated reduction of asparaginase activity.

Hypersensitivity Hypersensitivity reactions to pegaspargase, including life-threatening anaphylaxis, can occur during therapy, including in patients with known hypersensitivity to E. coli-derived asparaginase formulations. 8). 2). ). 8).

Depending on the severity of the symptoms, administration of antihistamines, corticosteroids and vasopressors may be indicated as a counter-measure. 8). Patients should be informed of the signs and symptoms of pancreatitis which, if left untreated, could become fatal.

If pancreatitis is suspected, Oncaspar should be discontinued; if pancreatitis is confirmed, Oncaspar should not be restarted. Serum amylase and/or lipase levels should be monitored frequently to identify early signs of pancreatic inflammation.

Blood glucose levels should be monitored, as impaired glucose tolerance may occur with concomitant use of Oncaspar with prednisone. 8). Oncaspar should be discontinued in patients with serious thrombotic events. Increased prothrombin time (PT), increased partial thromboplastin time (PTT), hypofibrinogenaemia and antithrombin III decrease can occur in patients receiving pegaspargase.

5), or when concomitant chemotherapy regimen including methotrexate, daunorubicin, corticosteroids is administered. When there is a marked decrease in fibrinogen or antithrombin III (ATIII) deficiency, consider appropriate replacement therapy.

8). Therefore, a close monitoring in children and adolescent patients is recommended in order to detect any clinical signs/symptoms of osteonecrosis. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment as per standard guidelines of treatment of ALL and supportive care principles Hepatic effects Combination therapy with Oncaspar and other hepatotoxic products can result in severe hepatic toxicity.

Caution is required when Oncaspar is given in combination with hepatotoxic products, especially if there is pre-existing hepatic impairment. Patients should be monitored for changes in liver function parameters. , imatinib) is combined with L-asparaginase therapy.

This should be taken into account when considering the use of Oncaspar in these patient populations. 8). Signs and symptoms of VOD include rapid weight gain, fluid retention with ascites, hepatomegaly, thrombocytopenia and rapid increase of bilirubin.

The identification of risk factors like pre-existing liver disease or history of VOD is essential for its prevention. Prompt recognition and appropriate management of VOD remain imperative. Patients who experience this condition should be treated according to standard medical practice.

Due to the risk of hyperbilirubinaemia, it is recommended to monitor bilirubin levels at baseline and prior to each dose. Central nervous system effects Combination therapy with Oncaspar can result in central nervous system toxicity.

8). Oncaspar may cause central nervous system signs and symptoms manifesting as somnolence, confusion, convulsions. 5). Myelosuppression Pegaspargase may cause myelosuppression, either directly or indirectly (by altering the myelosuppressive effects of other agents such as methotrexate or 6- […]

1. Severe hepatic impairment (bilirubin >3 times upper limit of normal [ULN]; transaminases >10 times ULN). History of serious thrombosis with prior L-asparaginase therapy. 4). 4).