Nelarabine

ARRANON is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens. ARRANON is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

Nelarabine is a prodrug of the deoxyguanosine analogue 9-β- D -arabinofuranosylguanine (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by ADA to ara-G, mono-phosphorylated by deoxyguanosine kinase and deoxycytidine kinase, and subsequently converted to the active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in leukemic blasts allows for incorporation into deoxyribonucleic acid (DNA), leading to inhibition of DNA synthesis and cell death. Other mechanisms may contribute to the cytotoxic and systemic toxicity of nelarabine.

• Adult Dose: 1,500 mg/m 2 administered by intravenous infusion over 2 hours on Days 1, 3, and 5 repeated every 21 days. • Pediatric Dose: 650 mg/m 2 administered by intravenous infusion over 1 hour daily for 5 consecutive days repeated every 21 days. • Discontinue treatment for neurologic reactions greater than or equal to Grade 2. • Dosage may be delayed for hematologic reactions. • Take measures to prevent hyperuricemia.

None. None.

Boxed warning (neurologic adverse reactions): Severe neurologic adverse reactions have been reported with the use of ARRANON ®. These adverse reactions have included altered mental states including severe somnolence, central nervous system effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis. • Neurologic Adverse Reactions: Severe neurologic reactions have been reported. Monitor for signs and symptoms of neurologic toxicity. • Hematologic Reactions: Complete blood counts including platelets should be monitored regularly. • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception, and advise males to use condoms. • Effects on Ability to Drive and Use Machines: Somnolence may occur.

The following clinically-significant adverse reactions are discussed in greater detail in other sections of the label: • Neurologic • Hematologic • Tumor Lysis Syndrome • Effects on Ability to Drive and Use Machines The most common (≥ 20%) adverse reactions were: • Adult: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea. • Pediatric: anemia, neutropenia, thrombocytopenia, and leukopenia. The most common (> 10%) neurological adverse reactions were: • Adult: somnolence, dizziness, peripheral neurologic disorders, hypoesthesia, headache, and paresthesia. • Pediatric: headache and peripheral neurologic disorders.

Administration of ARRANON in combination with adenosine deaminase (ADA) inhibitors, such as pentostatin, is not recommended. Administration in combination with adenosine deaminase (ADA) inhibitors, such as pentostatin, is not recommended.

Store ARRANON (nelarabine) Injection between 20°C and 25°C (68°F and 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature.