Nelarabine Disease Interactions

Severe neurologic adverse reactions have been reported with the use of nelarabine. Neurotoxicity is the dose-limiting toxicity of nelarabine. Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation may be at increased risk for neurologic adverse events. Close monitoring for neurologic adverse reactions is strongly recommended, when using nelarabine and therapy should be discontinued for neurologic adverse reactions of NCI Common Toxicity Criteria Grade 2 or greater.

Immunocompromised patients receiving nelarabine should avoid receiving live vaccines.

Leukopenia, thrombocytopenia, anemia, and neutropenia, including febrile neutropenia, have been associated with nelarabine therapy. Care should be instituted when using this agent in patients with hematologic complications. Complete blood counts including platelets should be monitored regularly.

The influence of hepatic impairment on the pharmacokinetics of nelarabine has not been evaluated. Because the risk of adverse reactions to this drug may be greater in patients with severe hepatic impairment (total bilirubin greater than 3 times upper limit of normal), it is recommended to closely monitor patients with severe liver dysfunction when treated with nelarabine.

Nelarabine is a prodrug of the cytotoxic deoxyguanosine analogue, 9-beta-D-arabinofuranosylguanine (ara-G). The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired or hemodialyzed patients. Nelarabine is excreted by the kidney to a small extent (5% to 10% of the administered dose). Ara-G is excreted by the kidney to a greater extent (20% to 30% of the administered nelarabine dose) and Ara-G clearance decreased as renal function decreased. Because the risk of adverse reactions to this drug may be greater in patients with moderate (CrCl 30 to 50 mL/min) or severe (CrCl less than 30 mL/min) renal impairment, it is recommended that these patients be closely monitored for toxicities when treated.

Patients receiving nelarabine should receive intravenous hydration according to standard medical practice for the management of hyperuricemia in patients at risk for tumor lysis syndrome. Consideration should be given to the use of allopurinol in patients at risk of hyperuricemia.