ONCASPAR

2 Recommended Dose and Dosage Adjustment 01/2023 7 WARNING AND PRECAUTIONS 01/2023 7 WARNING AND PRECAUTIONS 07/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ............................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................

4 4 DOSAGE AND ADMINISTRATION ................................................................................. 6 5 OVERDOSAGE..............................................................................................................

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). Depending on the severity of the symptoms, administration of antihistamines, corticosteroids and possibly circulation stabilising medical products, inotropes, and/or vasopressors are indicated as counter-measure. Other hypersensitivity reactions can include: angioedema, lip swelling, eye swelling, blood pressure decreased, bronchospasm, dyspnoea, hypotension, laryngeal edema, local erythema or swelling, pruritus, systemic rash, and urticaria.

Central Nervous System Toxicity Combination therapy with ONCASPAR can result in central nervous system toxicity. ONCASPAR may cause central nervous system dysfunctions manifesting as convulsion, and less frequently confusional state and somnolence (mildly impaired consciousness).

If ONCASPAR is used in association with neurotoxic products (such as vincristine and methotrexate), the patient should be closely monitored (see

– Hepatotoxicity and Abnormal Liver Function). • Known serious thrombosis during previous L-asparaginase therapy. • Known pancreatitis including pancreatitis related to previous L-asparaginase therapy (see 7 WARNINGS AND PRECAUTIONS – Pancreatitis).

• Known serious hemorrhagic events with previous L-asparaginase therapy. 1 Dosing Considerations ONCASPAR is employed as part of combination chemotherapy protocols with other antineoplastic agents. g. g. famotidine) 30-60 minutes prior to administration of ONCASPAR to decrease the risk and severity of both infusion and hypersensitivity reactions.

Steroid administration may also be considered in the premedication regimen. If premedication is administered, therapeutic drug monitoring should be considered to assess for silent inactivation (see 7 WARNINGS AND PRECAUTIONS). 6 m2 and under 21 years of age.

g. hyperbilirubinemia). Treatment may be monitored based on the trough serum L-asparaginase activity measured before the next administration of ONCASPAR. If L-asparaginase activity values fail to reach target levels, a switch to a different L-asparaginase preparation could be considered (see 7 WARNINGS AND PRECAUTIONS).

Special populations No formal studies were conducted in patients with renal or hepatic impairment. Recommended Monitoring and Dosage Modifications for Adverse Reactions Monitor patients at least weekly, with bilirubin, transaminases, glucose and clinical examinations until recovery from the cycle of therapy.

(see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests). If an adverse reaction should occur, modify treatment according to Table 1. 5 times the ULN Total bilirubin more than 10 times the ULN • Discontinue Oncaspar and do not make up for missed doses *Grades are in accordance with NCI-CTCAE ver.

0. *Grade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life-threatening. 4 Administration ONCASPAR can be given by intramuscular injection or intravenous infusion. For smaller volumes of ONCASPAR, the preferred route of administration is intramuscular.

ONCASPAR is contraindicated in patients with: • Anaphylactic or severe hypersensitivity reactions to the active substance or to any of the excipients. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the Product Monograph.

• Known serious allergic reactions to ONCASPAR. • Severe hepatic impairment (bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN) (see 7 WARNINGS AND PRECAUTIONS – Hepatotoxicity and Abnormal Liver Function).

• Known serious thrombosis during previous L-asparaginase therapy. • Known pancreatitis including pancreatitis related to previous L-asparaginase therapy (see 7 WARNINGS AND PRECAUTIONS – Pancreatitis). • Known serious hemorrhagic events with previous L-asparaginase therapy.