ATRIANCE

g. hydration, urine alkalinization, and prophylaxis with allopurinol) must be taken to prevent hyperuricemia associated with tumour lysis syndrome. g. g. antibiotics, blood and platelet transfusions) are recommended, as clinically indicated.

2 Recommended Dose and Dosage Adjustment Adults: The recommended adult dose of ATRIANCE is 1,500 mg/m²/day administered intravenously over 2 hours on days 1, 3, and 5, repeated every 21 days.

Children :

The recommended pediatric dose of ATRIANCE for children 15 years and younger is 650 mg/m²/day administered intravenously over 1 hour on days 1 to 5, repeated every 21 days. The optimal dosing regimen for patients between the ages of 16 and 21 years of age has not been determined.

The recommended duration of treatment has not been clearly established. In clinical trials, treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for bone marrow transplant, or the patient no longer continued to benefit from treatment.

The optimal schedule of concurrently administered nelarabine with intrathecal therapy and/or craniospinal irradiation has not been studied and is therefore not recommended (see 7 WARNINGS AND PRECAUTIONS, Neurologic; and 9 DRUG INTERACTIONS).

ATRIANCE has not been studied in patients with hepatic or renal dysfunction. No dose adjustment is recommended for CrCl50 mL/min. ). ATRIANCE (nelarabine) should be discontinued at the first sign of neurologic events of NCI Common Toxicity Criteria grade 2 or greater.

Administration of the next treatment cycle may be delayed for other toxicity including hematologic toxicity (See 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, 7 WARNINGS AND PRECAUTIONS, Neurologic, 8 ADVERSE REACTIONS). 3 Administration Nelarabine Injection is intended to be used without further dilution.

Nelarabine Injection is stable in polyvinylchloride (PVC) infusion bags and glass containers for up to 8 hours at up to 30°C. ATRIANCE solution should be inspected visually before use. Do not use if solution shows haziness, particulate matter, discolouration, or leakage.

2 Recommended Dose and Dosage Adjustment). Close monitoring for neurological events is strongly recommended. g. hydration, urine alkalinization, and prophylaxis with allopurinol) must be taken to prevent hyperuricemia associated with tumour lysis syndrome.

g. g. antibiotics, blood and platelet transfusions) are recommended, as clinically indicated. 2 Recommended Dose and Dosage Adjustment Adults: The recommended adult dose of ATRIANCE is 1,500 mg/m²/day administered intravenously over 2 hours on days 1, 3, and 5, repeated every 21 days.

Children :

The recommended pediatric dose of ATRIANCE for children 15 years and younger is 650 mg/m²/day administered intravenously over 1 hour on days 1 to 5, repeated every 21 days. The optimal dosing regimen for patients between the ages of 16 and 21 years of age has not been determined.

The recommended duration of treatment has not been clearly established. In clinical trials, treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for bone marrow transplant, or the patient no longer continued to benefit from treatment.

The optimal schedule of concurrently administered nelarabine with intrathecal therapy and/or craniospinal irradiation has not been studied and is therefore not recommended (see 7 WARNINGS AND PRECAUTIONS, Neurologic; and

4 Geriatrics. 2 CONTRAINDICATIONS ATRIANCE is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions ATRIANCE (nelarabine) Injection should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. This product is for intravenous use only.

Severe Neurologic Events:

These events included:  Altered mental states including severe somnolence  Central nervous system effects including convulsions and spinal cord necrosis. Patients with pre-existing CNS disease or patients treated previously or concurrently with intrathecal chemotherapy (including methotrexate) or previously with craniospinal irradiation may be at increased risk of more severe (≥ Grade 3) neurologic events (see 7 WARNINGS AND PRECAUTIONS, 4 DOSAGE and ADMINISTRATION, and 9 DRUG INTERACTIONS).

 Peripheral neuropathy including numbness, paresthesias, motor weakness, paralysis, craniospinal demyelination, and ascending peripheral neuropathies similar to Guillain-Barré ATRIANCE ® (nelarabine Injection) Product Monograph Page 5 of 38 syndrome Some of these neurologic adverse events are irreversible and fatal.

ATRIANCE should be discontinued at the first sign of neurologic events of NCI Common Toxicity Criteria grade 2 or greater (See 7 WARNINGS and PRECAUTIONS, Neurologic,

ATRIANCE is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.