Dosing and uses of Arranon (nelarabine)
Adult dosage forms and strengths
injectable solution
- 5mg/mL
Acute Lymphoblastic Leukemia & Lymphoma
Indicated for T-cell acute lymphoblastic leukemia & T-cell lymphoblastic lymphoma in patients after unsatisfactory treatment with at least 2 chemotherapeutic regimens
1500 mg/sq.meter IV over 2 hours on Days 1, 3, and 5; repeat q21Days
Monitor: Neurologic status
Chronic Lymphocytic Leukemia (Orphan)
Orphan indication sponsor
- GlaxoSmithKline LLC; Corporation Service Company, 2711 Centerville Road, Suite 400; Wilmington, DE 19808
Pediatric dosage forms and strengths
injectable solution
- 5mg/mL
Acute Lymphoblastic Leukemia & Lymphoma
Indicated for T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma
650 mg/sq.meter IV over 1 hour x5 consecutive days, repeat cycle q21Days
Monitor: Neurologic status
Arranon (nelarabine) adverse (side) effects
>10%
Anemia (>50%)
Neutropenia (>50%)
Thrombocytopenia (>50%)
Fatigue (in adults)
Somnolence (in adults)
Dizziness (in adults)
Headache
Peripheral neurologic disorder
Hypoesthesia
Paresthesia
Asthenia (in adults)
Pain (in adults)
Pyrexia (in adults)
Edema (in adults)
Petechiae (in adults)
Cough (in adults)
Dyspnea (in adults)
Pleural effusion (in adults)
Diarrhea (in adults)
Nausea (in adults)
Vomiting
Constipation (in adults)
Leukopenia (in peds)
Hepatobiliary d/o (in peds)
Myalgia (in adults)
1-10% (selected)
Seizures (in peds)
Ataxia (in adults)
Insomnia (in adults)
Anorexia (in adults)
Decreased Ca/Mg (in peds)
Postmarketing Reports
Fatal opportunistic infections
Tumor lysis syndrome
Demyelination and ascending peripheral neuropathies (similar to Guillain-Barré syndrome)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Administer intravenously only
Neurologic events
- Severe neurologic events such as altered mental states including severe somnolence, CNS effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis have been reported
- Events associated with demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome have also been reported
- These events are not always reversible following cessation of therapy
- Monitor patients closely for neurologic events and discontinue therapy for neurologic events of National Cancer Institute (NCI) Common Toxicity Criteria grade 2 or greater
Contraindications
Hypersensitivity
Cautions
Risk of severe neurological problems, sometimes irreversible even on drug discontinuation
Discontinue if CTC grade 2 or higher neurotoxicity
Avoid pregnancy
Give IV hydration & consider allopurinol to pts at risk for tumor lysis synd & concomitant hyperuricemia
Do not administer live vaccines to immunocompromised patients
Pregnancy and lactation
Pregnancy category: d
Lactation: do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Arranon (nelarabine)
Peak Plasma (adult dose): nelarabine 2-8 mcg/mL; ara-G 26-37 mcg/mL
Half-Life, Elimination (adult dose): nelarabine 30 min; ara-G 3 hr
Metabolism: converted to ara-G & methylguanine which are then hydrolyzed or demethylated to guanine & eventually to uric acid & allantoin
Excretion: partially in urine
Mechanism of action
Converted first to the nucleoside analog, ara-G, & subsequently to the nucleotide analog, ara-GTP, which incorporates into DNA & leads to inhibition of DNA replication & cell death
Administration
IV Administration
Do not dilute
Appropriate dose is transferred to infusion bags or glass containers & infused over 2 hr (adults) or 1 hr (peds)
