Nelarabine (Monograph)
Brand name: Arranon
Drug class: Antineoplastic Agents
VA class: AN300
Chemical name: 2-Amino-9-β-D-arabinofuranosyl-6-methoxy-9H-purine
Molecular formula: C11H15N5O5
CAS number: 121032-29-9
Warning
- Neurotoxicity
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Severe, possibly irreversible, neurologic events (e.g., somnolence, confusion, seizures, peripheral neuropathy). Craniospinal demyelination and ascending peripheral neuropathy (similar in presentation to Guillain-Barré syndrome) reported. (See Neurotoxicity under Cautions.)
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Closely monitor for adverse neurologic effects; discontinue therapy for neurologic events of NCI Common Toxicity Criteria grade ≥2.
- Experience of Supervising Clinician
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For IV use only; administer only under the supervision of qualified clinicians experienced in the use of cancer chemotherapeutic agents.
Introduction
Antimetabolite antineoplastic agent.
Uses for Nelarabine
Acute Lymphocytic Leukemia (ALL)
Treatment of acute T-cell lymphocytic (lymphoblastic) leukemia (ALL) and T-cell lymphoblastic lymphoma in patients whose disease is refractory to or has relapsed after ≥2 prior chemotherapy regimens (designated an orphan drug by FDA for these conditions).
Nelarabine Dosage and Administration
General
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Consult specialized references for procedures for proper handling and disposal of antineoplastics.
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Appropriate measures (e.g., administration of IV fluids, allopurinol, and alkalinization of urine) should be taken to prevent hyperuricemia of tumor lysis syndrome. (See Tumor Lysis Syndrome under Cautions.)
Administration
IV Administration
Administer by IV infusion.
Nelarabine injection should not be diluted prior to administration.
Withdraw appropriate dose from the required number of vials and transfer into empty PVC infusion bags or glass containers prior to administration.
Rate of Administration
Adults: Administer by IV infusion over 2 hours.
Pediatric patients: Administer by IV infusion over 1 hour.
Dosage
Pediatric Patients
Acute Lymphocytic Leukemia
Relapsed or Refractory T-cell ALL or T-cell Lymphoblastic Lymphoma
IV650 mg/m2 daily for 5 consecutive days; repeat every 21 days.
Optimal duration of treatment not established. In clinical studies, treatment was continued until evidence of disease progression, unacceptable toxicity, bone marrow transplantation, or lack of clinical benefit was observed.
Adults
Acute Lymphocytic Leukemia
Relapsed or Refractory T-cell ALL or T-cell Lymphoblastic Lymphoma
IV1500 mg/m2 on days 1, 3, and 5; repeat every 21 days.
Optimal duration of treatment not established. In clinical studies, treatment was continued until evidence of disease progression, unacceptable toxicity, bone marrow transplantation, or lack of clinical benefit was observed.
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.
Renal Impairment
No dosage adjustment required in patients with mild renal impairment (Clcr ≥50 mL/minute); not studied in patients with moderate to severe renal impairment.
Geriatric Patients
No specific dosage recommendations at this time.
Cautions for Nelarabine
Contraindications
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Known hypersensitivity to nelarabine or any ingredient in the formulation.
Warnings/Precautions
Warnings
Adequate Patient Monitoring and Evaluation
Administer only under the supervision of qualified clinicians experienced in the use of cancer chemotherapy agents.
Neurotoxicity
Potentially irreversible and dose-limiting neurotoxicity, usually manifested by somnolence, confusion, seizures, and peripheral neuropathy (ranging from numbness to motor weakness and paralysis). Coma, status epilepticus, craniospinal demyelination, and ascending peripheral neuropathy (similar in presentation to Guillain-Barré syndrome) reported.
Increased risk of neurotoxicity in patients who have received prior or concomitant intrathecal chemotherapy or prior craniospinal irradiation; discontinue therapy in patients experiencing neurologic events of NCI Common Toxicity Criteria grade ≥2.
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity demonstrated in animals. Avoid pregnancy during therapy; if used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.
General Precautions
Hematologic Effects
Leukopenia, thrombocytopenia, anemia, and neutropenia reported. Perform CBC, including platelet count, regularly while patient is receiving the drug.
Tumor Lysis Syndrome
May occur as a result of nelarabine therapy; consider measures (e.g., hydration, urinary alkalinization, allopurinol) to prevent hyperuricemia in patients at risk for tumor lysis syndrome.
Immunization
Avoid administration of live virus vaccines during therapy.
Specific Populations
Pregnancy
Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether nelarabine or ara-G is distributed into milk; discontinue nursing because of potential risk to nursing infants.
Pediatric Use
Safety and efficacy established in patients 2.5–21 years of age.
Geriatric Use
Possible inreased incidence of neurologic effects compared with younger adults. (See Neurotoxicity under Cautions.)
Hepatic Impairment
Not studied in patients with hepatic impairment; possible increased risk of adverse reactions in patients with severe hepatic impairment (serum bilirubin >3 mg/dL).
Renal Impairment
Possible increased risk of adverse reactions in patients with severe renal impairment (Clcr <30 mL/minute).
Common Adverse Effects
In adults: Myelosuppresion, somnolence, dizziness, peripheral neurologic disorders, hypoesthesia, headache, paresthesia, fatigue, pyrexia, asthenia, edema, pain, myalgia, nausea, diarrhea, vomiting, constipation, cough, dyspnea, pleural effusion, petechiae.
In pediatric patients: Myelosuppression, headache, peripheral neurologic disorders, elevated serum transaminase concentrations, hyperbilirubinemia, hypokalemia, hypoalbuminemia, vomiting.
Drug Interactions
Does not appear to inhibit CYP isoenzymes, including 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro.
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Adenosine deaminase inhibitors (i.e., pentostatin) |
Possible decrease in nelarabine efficacy and/or change in adverse effect profile for either drug |
Concomitant use not recommended |
Fludarabine |
Pharmacokinetics of nelarabine not altered |
Nelarabine Pharmacokinetics
Distribution
Extent
Extensively distributed throughout the body.
Not known whether nelarabine crosses the placenta or is distributed into milk.
Plasma Protein Binding
<25%.
Elimination
Metabolism
Metabolized to ara-G, principally via O-demethylation by adenosine deaminase; ara-G undergoes further hydrolysis to guanine.
Elimination Route
Nelarabine and ara-G are partially eliminated by the kidneys.
Half-life
Nelarabine: 0.5 hour.
Ara-G: 3 hours.
Special Populations
In pediatric patients, clearance of nelarabine is increased by 30%; ara-G clearance is comparable to that in adults.
Renal impairment may reduce clearance.
In white patients, clearance and volume of distribution of nelarabine increased by 10%; clearance and volume of distribution of ara-G decreased by 15–20% when compared with black patients.
Stability
Storage
Parenteral
Solution
25°C (may be exposed to 15–30°C).
Stable in PVC bags and glass containers at ≤30°C for up to 8 hours.
Actions
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Prodrug of the deoxyguanosine analog ara-G, which is subsequently converted to the active 5′-triphosphate, ara-GTP.
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Ara-GTP accumulates in leukemic blasts and incorporates into DNA, inducing fragmentation and apoptosis.
Advice to Patients
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Risk of neurotoxicity; importance of informing clinician immediately if any changes in mental status, signs and symptoms of peripheral neuropathy (e.g., tingling or numbness in extremities, unsteadiness while walking, difficulty with fine motor coordination, increased tripping, weakness when rising from a low chair or climbing stairs), or seizures occur.
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Risk of sleepiness; avoid driving or operating machinery.
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Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.
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Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy; advise pregnant women of risk to the fetus.
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Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
Injection, for IV use |
5 mg/mL (250 mg) |
Arranon |
GlaxoSmithKline |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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