Adult Dosing

T-cell ALL/ T-cell LBL refractory/relapse

• 1500 mg/m² IV over 2 hrs on days 1, 3 and 5 , repeated q21 days

• Nelarabine is administered undiluted
• See prescribing information for details about dose adjustments based on toxicity
• Discontinue treatment for grade 2 neurologic reactions
• Dosage may be delayed for hematologic reaction

Pediatric Dosing

T-cell ALL/ T-cell LBL refractory/relapse

• 650 mg/m² IV over 1 hr for 5 consecutive days repeated q21 days

Note:

• Nelarabine is administered undiluted
• See prescribing information for details about dose adjustments based on toxicity

[Outline]

• Adult Dosing
• Pediatric Dosing

• T-cell acute lymphoblastic leukemia (T-cell ALL) and T-cell lymphoblastic lymphoma (T-cell LBL) not responded or relapsed following treatment with at least two chemotherapy regimens

• Hypersensitivity to any of the ingredients of the product
• Pregnancy

• Severe neurological events including altered mental states, severe somnolence, CNS effects viz convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis have been reported. Events associated with demyelination or ascending peripheral neuropathies similar in appearance to Guillian-Barre syndrome have also occurred
• Complete recovery from these events has not always occurred with cessation of therapy; monitor closely for neurologic events and discontinue the treatment if events of NCI common toxicity criteria >grade 2 or greater occurs

Renal Dose Adjustment: (Based on CrCl)

• CrCl <30 mL/min: Caution advised; dose adjustments not defined

Hepatic Dose Adjustment:

• Severe impairment (bilirubin >3.0 mg/dL): Caution advised; dose adjustments not defined

See Supplemental Patient Information

• Severe neurotoxicity has occurred with nelarabine, closely monitor patients for signs and symptoms of neurologic toxicity[US Black Box Warning]
• Patients with history of intrathecal chemotherapy or previous craniospinal irradiation are at increased risk for neurologic adverse events
• Nelarabine therapy causes leukopenia, thrombocytopenia, anemia, and neutropenia, including febrile neutropenia, monitor CBC including platelet count regularly
• Give IV hydration for the management of hyperuricemia to patients on nelarabine therapy at risk for tumor lysis; consider use of allopurinol in patients at risk of hyperuricemia
• Avoid administration of live vaccines to immunocompromised patients

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• History of intrathecal chemotherapy
• History of craniospinal irradiation
• Patients with child-bearing potential
• Elderly patients

Supplemental Patient Information

• Patients should be advised not to operate hazardous machinery, including automobiles during nelarabine therapy as it may cause somnolence
• Women of childbearing should be advised to use effective contraceptives

Pregnancy Category:D

Breastfeeding: Safety Unknown; Because of the potential for possible serious adverse reactions in nursing infants a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• HEMA: Anemia, thrombocytopenia, neutropenia, febrile neutropenia, leukopenia
• CV: Sinus tachycardia, chest pain, hypotension, petechiae
• CNS: Neurotoxicity, somnolence, dizziness, peripheral neurologic disorders, neuropathy, hypoesthesia, headache, paresthesia, ataxia, tremor, amnesia, dysgeusia, balance disorder, sensory loss, paralysis, Guillain-Barre syndrome, coma, cerebral hemorrhage, seizures, demyelinating CNS diseases
• PSYCHIATRY: Confusional state, insomnia, depression
• RESP: Pneumonia, Cough, dyspnea, pleural effusion, epistaxis, exertional dyspnea, wheezing
• EENT: Sinusitis
• HEPA: Increased AST
• GI: Nausea, diarrhea, vomiting, constipation, abdominal pain, stomatitis, abdominal distension
• METABOLIC: Anorexia, dehydration, hyperglycemia
• MUSC: Myalgia, arthralgia, back pain, muscular weakness, pain in extremity
• LOCAL: Pain
• MISC: Fatigue, pyrexia, asthenia, peripheral edema, rigors, abnormal gait, infection

• Antineoplastic Agent; Converted to ara-G and then metabolized to ara-GTP, accumulates in leukemic blasts and is incorporated into DNA resulting in inhibition of DNA synthesis and cell death
• Metabolized to ara-G by O-demethylation
• Partially eliminated by the kidneys (6.6% nelarabine; 27% ara-G)
• Half-life
• Nelarabine: 18 mins
• Ara-G: 3.2 hrs

US Trade Name(s)

• Arranon

US Availability

Arranon

• INJ: 5 mg/mL (50 mL vials)

Canadian Trade Name(s)

• Atriance

Canadian Availability

Atriance

• INJ: 5 mg/mL (50 mL vials)

UK Trade Name(s)

• Atriance

UK Availability

Atriance

• INJ: 5 mg/mL (50 mL vials)

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Antineoplastics

Antimetabolites