nelarabine: clinical use

Prescribing considerations

• Restrict use to specialist supervision by clinicians experienced with cytotoxic agents.
• Assess baseline neurological status and promptly investigate new central or peripheral neurological symptoms.
• Review previous intrathecal chemotherapy and craniospinal irradiation because these may increase neurological risk.
• Assess renal and hepatic function; evidence in impairment is limited, and closer toxicity surveillance is required.
• Consider tumour-lysis risk and appropriate hydration and urate-lowering management.
• Discuss contraception, possible fertility effects and family planning before treatment.

Contraindications and cautions

• Hypersensitivity to nelarabine or any formulation excipient.
• Use particular caution with renal or hepatic impairment, pre-existing neurological problems and older age.
• Concurrent intrathecal chemotherapy, craniospinal irradiation and live vaccines are not recommended.

Monitoring

• Regular complete blood counts, including platelets.
• Frequent clinical assessment for somnolence, confusion, seizures, ataxia, sensory change, weakness and gait disturbance.
• Renal function, liver function and metabolic markers according to clinical context.
• Evidence of infection, bleeding, tumour lysis and muscle injury.

Clinical pharmacology

Nelarabine is an ara-G prodrug. Adenosine deaminase converts it to ara-G, which is phosphorylated intracellularly to ara-GTP. Preferential accumulation and DNA incorporation in T-lymphoblasts inhibits DNA synthesis. Nelarabine and ara-G are partly renally eliminated; clinically important CYP inhibition is not expected from in-vitro findings.

Formulation and product differences

• The selected UK product is a clear, colourless solution for intravenous infusion.
• It is ready to use and must not be diluted before transfer to a compatible infusion container.
• The formulation contains sodium and has no preservative listed.

Solution for infusion

Route: Intravenous

Strengths: 5 mg/mL