Medically reviewed by Drugs.com. Last updated on Aug 19, 2019.
(nel AY re been)
- 2-Amino-6-Methoxypurine Arabinoside
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Arranon: 5 mg/mL (50 mL)
Brand Names: U.S.
- Antineoplastic Agent, Antimetabolite
- Antineoplastic Agent, Antimetabolite (Purine Analog)
Nelarabine, a prodrug of ara-G, is demethylated by adenosine deaminase to ara-G and then converted to ara-GTP. Ara-GTP is incorporated into the DNA of the leukemic blasts, leading to inhibition of DNA synthesis and inducing apoptosis. Ara-GTP appears to accumulate at higher levels in T-cells, which correlates to clinical response.
Nelarabine: Pediatric patients: 213 ± 358L/m2; Adults: 197 ± 216 L/m2
Ara-G: Pediatric patients: 33 ± 9.3 L/m2; Adults: 50 ± 24 L/m2
Hepatic; demethylated by adenosine deaminase to form ara-G (active); also hydrolyzed to form methylguanine. Both ara-G and methylguanine metabolized to guanine. Guanine is deaminated into xanthine, which is further oxidized to form uric acid, which is then oxidized to form allantoin.
Urine (nelarabine 5% to 10%, Ara-G 20% to 30%)
Nelarabine clearance is ~30% higher in pediatric patients (259 ± 409 L/hour/m2) than in adults (197 ± 189 L/hour/m2); Ara-G clearance in pediatric patients (11.3 ± 4.2 L/hour/m2) is similar to adults (10.5 ± 4.5 L/hour/m2)
Time to Peak
Adults: 3 to 25 hours (of day 1)
Pediatric patients: Nelarabine: 13 minutes, Ara-G: 2 hours; Adults: Nelarabine: 18 minutes, Ara-G: 3.2 hours
Nelarabine and ara-G: <25%
Special Populations: Renal Function Impairment
Clearance of Ara-G is reduced 15% in patients with mild renal impairment (CrCl 50 to 80 mL/minute) and 40% in patients with moderate renal impairment (CrCl <50 mL/minute), compared to patients with normal renal function.
Special Populations: Elderly
Reduced renal function in elderly patients may reduce Ara-G clearance.
Special Populations: Race
Mean clearance and Vd values tended to be higher in white patients than in black patients (by approximately 10%). The opposite is true for ara-G; mean apparent Cl and Vd values tended to be lower in white patients than in black patients (by approximately 15% to 20%).
Use: Labeled Indications
T-cell acute lymphoblastic leukemia/lymphoma: Treatment of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma in patients ≥1 year of age following at least 2 chemotherapy regimens
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to nelarabine or any component of the formulation.
Note: Adequate hydration and prophylactic antihyperuricemic therapy are recommended to prevent tumor lysis syndrome.
T-cell acute lymphoblastic leukemia/lymphoma: IV: 1,500 mg/m2/dose on days 1, 3, and 5; repeat every 21 days until a transplant candidate, disease progression, unacceptable toxicity, or until no longer benefiting from therapy.
Refer to adult dosing. Age ≥65 years may be associated with increased neurotoxicity; monitor closely.
Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
T-cell acute lymphoblastic leukemia (ALL), T-cell lymphoblastic lymphoma, relapsed/refractory: Infants, Children, and Adolescents: IV: 650 mg/m2/dose on days 1 through 5; repeat cycle every 21 days until transplant, disease progression, or unacceptable toxicity
Dosage adjustment for toxicity: Infants, Children, and Adolescents:
Neurologic toxicity ≥grade 2: Discontinue treatment
Hematologic or other (non-neurologic) toxicity: Consider treatment delay
Dosing: Adjustment for Toxicity
Neurologic toxicity ≥ grade 2: Discontinue treatment.
Hematologic or other (non-neurologic) toxicity: Consider treatment delay.
Administer undiluted; reconstitution is not required; the appropriate dose should be added to an empty polyvinylchloride bag or glass container.
Adequate IV hydration and prophylactic antihyperuricemic therapy are recommended to prevent tumor lysis syndrome.
Infuse over 2 hours on days 1, 3, and 5.
Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Stable in a polyvinylchloride infusion bag or a glass container for up to 8 hours at 30°C (86°F).
Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification
Pentostatin: May diminish the antineoplastic effect of Nelarabine. Conversion of nelarabine, a pro-drug, to its active form may be inhibited by pentostatin. Avoid combination
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Pediatric adverse reactions fell within a range similar to adults except where noted.
Cardiovascular: Peripheral edema (15%), edema (11%)
Central nervous system: Fatigue (50%), drowsiness (7% to 23%), dizziness (21%), peripheral neuropathy (12% to 21%; grades 2/3: 11% to 14%; may be similar to Guillain-Barré syndrome), headache (15% to 17%), hypoesthesia (6% to 17%), paresthesia (4% to 15%), pain (1% to 11%; includes neuropathic pain)
Endocrine & metabolic: Hypokalemia (11%)
Gastrointestinal: Nausea (41%), diarrhea (22%), vomiting (10% to 22%), constipation (21%)
Hematologic & oncologic: Anemia (95% to 99%; grade 4: 10% to 14%), neutropenia (81% to 94%; grade 4: children 62%, adults 49%), thrombocytopenia (86% to 88%; grade 4: 22% to 32%), leukopenia (38%; grade 4: 7%), febrile neutropenia (12%; grade 4: 1%), petechia (12%)
Hepatic: Increased serum transaminases (12%)
Neuromuscular & skeletal: Weakness (6% to 17%), myalgia (13%)
Respiratory: Cough (25%), dyspnea (7% to 20%)
Miscellaneous: Fever (23%)
1% to 10%:
Cardiovascular: Hypotension (8%), sinus tachycardia (8%), chest pain (5%)
Central nervous system: Ataxia (1% to 9%), confusion (8%), myasthenia (8%), rigors (8%), insomnia (7%), abnormal gait (6%), depression (6%), impaired consciousness (6%), noncardiac chest pain (5%), motor dysfunction (4%), amnesia (3%), equilibrium disturbance (2%), sensory disturbance (1% to 2%), disturbance in attention (1%), dysarthria (1%), hydrocephalus (1%), hypertonia (1%), hyporeflexia (1%), lethargy (1%), mental status changes (1%), nerve palsy (1%), paralysis (1%; including nerve paralysis), sciatica (1%), speech disturbance (1%), aphasia, brain disease, cerebral hemorrhage, coma, hemiparesis, intracranial hemorrhage, leukoencephalopathy, loss of consciousness, seizure
Endocrine & metabolic: Decreased serum albumin (10%), hypocalcemia (8%), dehydration (7%), hyperglycemia (6%), hypoglycemia (6%), hypomagnesemia (6%)
Gastrointestinal: Abdominal pain (9%), anorexia (9%), stomatitis (8%), abdominal distention (6%), dysgeusia (3%)
Hepatic: Increased serum bilirubin (10%), increased serum AST (6%)
Infection: Infection (5% to 9%)
Neuromuscular & skeletal: Arthralgia (9%), back pain (8%), limb pain (7%), tremor (4% to 5%)
Ophthalmic: Blurred vision (4%), nystagmus (1%)
Renal: Increased serum creatinine (6%)
Respiratory: Pleural effusion (10%), epistaxis (8%), pneumonia (8%), sinusitis (7%), wheezing (5%), sinus headache (1%)
<1%, postmarketing, and/or case reports: Demyelinating disease (craniospinal demyelination), increased creatine phosphokinase, opportunistic infection, pneumothorax, progressive multifocal leukoencephalopathy, rhabdomyolysis, tumor lysis syndrome
ALERT: U.S. Boxed WarningNeurologic adverse reactions:
Severe neurologic adverse reactions have been reported with the use of nelarabine. These reactions have included altered mental states, including severe somnolence; CNS effects, including convulsions; and peripheral neuropathy, ranging from numbness and paresthesias to motor weakness and paralysis. There have also been reports of adverse reactions associated with demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome.
Full recovery from these reactions has not always occurred with cessation of therapy with nelarabine. Monitor frequently for signs and symptoms of neurologic toxicity during treatment with nelarabine. Discontinue nelarabine for neurologic reactions of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 or greater.
Concerns related to adverse effects:
• Bone marrow suppression: Leukopenia, thrombocytopenia, anemia, and neutropenia (including neutropenic fever) are associated with nelarabine treatment. Monitor blood counts regularly.
• CNS depression: Nelarabine may cause somnolence during and for several days after treatment, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Neurotoxicity: [US Boxed Warning]: Severe neurotoxicities, including mental status changes, severe somnolence, seizures, and peripheral neuropathy (ranging from numbness and paresthesias to motor weakness and paralysis), have been reported. Monitor frequently during treatment for signs and symptoms of neurotoxicity; discontinue if ≥ grade 2. Adverse reactions associated with demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome have also been reported. Neurologic toxicities may not fully return to baseline after treatment cessation. Common signs and symptoms of neurotoxicity include somnolence, headache, paresthesia, dysesthesia, dizziness, neuropathy (sensory and motor), cerebellar disturbances, tremor, and, in severe cases, coma, status epilepticus, craniospinal demyelination, and ascending neuropathy. Symptom onset from start of first infusion is often within a median of 5 to 8 days (range: 1 to 269 days), with a median duration of 2 to 6 days (range: 1 to 393 days). Monitor closely for neurologic toxicity during and for at least 24 hours after each treatment. Risk of neurotoxicity may be increased in patients with concurrent or previous intrathecal chemotherapy or prior craniospinal irradiation.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) may occur as a consequence of leukemia treatment. May lead to life-threatening acute renal failure. Ensure adequate hydration prior to and during treatment to prevent hyperuricemia and TLS; consider prophylactic antihyperuricemic therapy. Monitor closely.
• Hepatic impairment: Monitor closely for toxicities. Risk of adverse reactions may be higher with severe hepatic dysfunction.
• Renal impairment: Monitor closely for toxicities. Ara-G clearance may be reduced with renal dysfunction and the risk of adverse reactions may be higher in patients with moderate to severe impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Vaccines: Avoid administration of live vaccines to immunocompromised patients.
CBC with differential, liver and kidney function; verify pregnancy status prior to therapy initiation in females of reproductive potential; monitor closely for neurologic toxicity (severe somnolence, seizure, peripheral neuropathy, confusion, ataxia, paresthesia, hypoesthesia, coma, or craniospinal demyelination), especially during and for at least 24 hours after each treatment; monitor for signs and symptoms of tumor lysis syndrome; monitor hydration status
Based on its mechanism of action and findings in animal reproduction studies, nelarabine may cause fetal harm if administered during pregnancy. Verify pregnancy status in females of reproductive potential prior to therapy initiation. Females of reproductive potential should use effective contraception during nelarabine therapy. Male patients (including those who have had vasectomies) with female partners of reproductive potential should use condoms during nelarabine treatment and for 3 months after the last nelarabine dose.
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided during the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation. Specific use of nelarabine is not discussed (Peccatori 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, constipation, diarrhea, back pain, abdominal pain, mouth irritation, mouth sores, abdominal swelling, lack of appetite, insomnia, headache, or joint pain. Have patient report immediately to prescriber signs of infection, signs of dehydration, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), shortness of breath, pale skin, bruising, bleeding, severe loss of strength and energy, confusion, severe fatigue, burning or numbness feeling, change in balance, seizures, difficulty with performing functions of daily living, abnormal gait, chest pain, tachycardia, swelling in the arms or legs, severe dizziness, passing out, severe muscle pain, muscle weakness, depression, or signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about nelarabine
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- En Español
- Drug class: antimetabolites
Other brands: Arranon