Nelarabine (2 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INTRAVENOUS.
Brand Names
- ARRANON
- NELARABINE
Boxed Warning
Severe neurologic adverse reactions have been reported with the use of nelarabine. 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. There have also been reports of adverse reactions associated with demyelination, and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome [see Warnings and Precautions (5.1)]. Full recovery from these adverse reactions has not always occurred with cessation of therapy with nelarabine. Monitor frequently for signs and symptoms of neurologic toxicity during treatment with nelarabine. Discontinue nelarabine for neurologic adverse reactions of NCI Common Toxicity Criteria for Adverse Events (CTCAE) Grade 2 or greater [see Warnings and Precautions (5.1)].
Indications and Usage
Nelarabine injection 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.
Contraindications
None.
Adverse Reactions
The following clinically-significant adverse reactions are discussed in greater detail in other sections of the label: Neurologic [see Boxed Warning, Warnings and Precautions (5.1)] Hematologic [see Warnings and Precautions (5.2)] Tumor Lysis Syndrome [see Warnings and Precautions (5.4)] Effects on Ability to Drive and Use Machines [see Warnings and Precautions (5.6)]
Drug Interactions
Administration of nelarabine in combination with adenosine deaminase (ADA) inhibitors, such as pentostatin, is not recommended [see Clinical Pharmacology (12.3)].
Mechanism of Action
Nelarabine is a prodrug of the deoxyguanosine analogue 9-β-D-arabinofuranosylguanine (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by adenosine deaminase (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.
Overdosage
There is no known antidote for overdoses of nelarabine. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death. In the event of overdose, supportive care consistent with good clinical practice should be provided. At a dose of 2,200 mg/m2 given on Days 1, 3, and 5 every 21 days, 2 patients developed a significant Grade 3 ascending sensory neuropathy. Magnetic resonance imaging evaluations of the 2 patients demonstrated findings consistent with a demyelinating process in the cervical spine.