Trade Names:Arranon- Injection 250 mg (5 mg/mL)
Converted to ara-G, then activated to ara-GTP. Ara-GTP accumulates in leukemic blasts and is incorporated into DNA, leading to inhibition of DNA synthesis and cell death.
C max of ara-G generally occurs at end of nelarabine infusion.
Nelarbine and ara-G are extensively distributed. Protein binding is less than 25%. Nelarabine Vd at steady state is 197 L/m 2 (adults) and 213 L/m 2 (children). Ara-G Vd at steady state is 50 L/m 2 (adults) and 33 L/m 2 (children). Intracellular C max for ara-GTP occurs within 3 to 25 h on day 1. AUC of intracellular ara-GTP is 532 times higher than nelarabine and 14 times higher than ara-G.
Rapid and extensive conversion of nelarabine to ara-G by O-demethylation. Ara-G is hydrolyzed to guanine, which is N-deaminated to xanthine and then oxidized to uric acid.
Rapidly eliminated from plasma. Apparent Cl is 10.5 L/h/m 2 (adults) and 11.3 L/h/m 2 (children). Partially eliminated by kidneys (6.6% nelarabine; 27% ara-g); t ½ is approximately 30 min (nelarabine) and 3 h (ara-G).
Cl reduced 15% in patients with mild renal function impairment (CrCl 50 to 80 mL/min) and 40% in patients with moderate renal function impairment (CrCl less than 50 mL/min).Elderly
Reduced renal function in elderly patients may reduce ara-G Cl.
Treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in patients whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens.
IV 1,500 mg/m 2 over 2 h on days 1, 3, and 5; repeated every 21 days.Leukemia/LymphomaChildren
IV 650 mg/m 2 over 1 h daily for 5 consecutive days; repeated every 21 days.Duration of TherapyAdults and children
IV Duration of treatment has not been clearly established. Generally, treatment is continued until there is evidence of disease progression, the patient experiences unacceptable toxicity, the patient no longer continues to benefit from treatment, or the patient becomes a candidate for bone marrow transplantation.
Store unopened vials at controlled room temperature (59° to 86°F). Nelarabine is stable in glass infusion containers and PVC infusion bags for up to 8 h if stored at room temperatures up to 86°F.
None well documented.
None well documented.
Chest pain, hypotension, petechiae, sinus tachycardia (at least 5%).
Abnormal gait, asthenia, confusion, depression, fatigue, insomnia (at least 5%); amnesia, ataxia, balance disorder, convulsions, depressed level of consciousness, dizziness, grand mal convulsions, headache, hypesthesia, motor dysfunction, motor neuropathy, nervous system disorder, paresthesia, peripheral neuropathy, sensory loss, sensory neuropathy, somnolence, status epilepticus, tremor (at least 2%); abnormal coordination, burning sensation, disturbance in attention, dysarthria, hyporeflexia, neuropathic pain, nystagmus, peroneal nerve palsy, sciatica, sensory disturbance, speech disorder (1%); demyelination and ascending peripheral neuropathies similar to Guillain-Barré syndrome.
Epistaxis, sinusitis (at least 5%); blurred vision (4%); sinus headache (1%).
Abdominal distension and pain, constipation, diarrhea, nausea, stomatitis, vomiting (at least 5%); dysgeusia (at least 2%).
Anemia, febrile neutropenia, leukopenia, neutropenia, thrombocytopenia (at least 5%).
Decreased albumin, calcium, glucose, magnesium, or potassium (at least 5%); increased AST, bilirubin, creatinine, or transaminases (at least 5%).
Dehydration, hyperglycemia (at least 5%).
Arthralgia, back pain, muscular weakness, myalgia, pain in extremities, rigors (at least 5%).
Cough, dyspnea, exertional dyspnea, pleural effusion, pneumonia, wheezing (at least 5%).
Edema, infection, noncardiac chest pain, pain, peripheral edema, pyrexia (at least 5%).
Severe neurologic events have been reported. Events included altered mental status (eg, somnolence, confusion), CNS effects (eg, ataxia, convulsions), peripheral neuropathy, ranging from numbness and paresthesias to motor weakness and paralysis, and demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome. Patients treated previously or concurrently with intrathecal chemotherapy, or previously with craniospinal irradiation, may be at increased risk.
Full recovery from these events has not always occurred with cessation of therapy.
Closely monitor patients for neurologic events. Monitor CBC and platelet count regularly.
Category D .
May be at increased risk for neurologic adverse reactions.
Risk of reactions may be greater in patients with severe renal function impairment (CrCl less than 30 mL/min); closely monitor these patients for toxicity.
Risk of reactions may be greater in patients with severe hepatic function impairment (bilirubin greater than 3 mg/dL); closely monitor these patients for toxicity.
May cause somnolence.
Discontinue therapy for neurologic events of NCI Common Toxicity Criteria grade 2 or higher. Dosage may be delayed for other toxicities, including hematologic toxicity.
Anemia, leukopenia, neutropenia, and thrombocytopenia, including febrile neutropenia, have been associated with nelarabine therapy.
Avoid administering live vaccines to immunocompromised patients.
Provide appropriate measures (eg, IV hydration, prophylaxis with allopurinol, urine alkalinization) to prevent hyperuricemia of tumor lysis syndrome.
Myelosuppression, neurotoxicity (possibly including coma, paralysis), potentially death.
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