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.
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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling, (although ARA-G clearance is decreased as renal function declines, data is insufficient for a dosing recommendation); monitor closely.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); closely monitor with severe impairment (total bilirubin >3 times ULN).
(For additional information see "Nelarabine: Pediatric drug information")
Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. Adequate IV hydration and prophylactic antihyperuricemic therapy are recommended to prevent tumor lysis syndrome.
T-cell acute lymphoblastic leukemia (T-ALL); newly diagnosed, high risk: Limited data available: Note: Nelarabine was not administered within 2 weeks of other chemotherapies known to cause central or peripheral toxicities.
Children and Adolescents: IV:
Consolidation: 650 mg/m2/dose on days 1 through 5 and 43 through 47 of a 77-day cycle (in combination with vincristine, pegaspargase, cyclophosphamide, cytarabine, mercaptopurine, and intrathecal methotrexate) (Winter 2015; Winter 2018).
Delayed intensification: 650 mg/m2/dose on days 29 through 33 of a 63-day cycle (in combination with vincristine, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, thioguanine, doxorubicin, and intrathecal methotrexate) (Winter 2015; Winter 2018).
Maintenance: 650 mg/m2/dose on days 29 through 33 of an 84-day cycle; during first 3 cycles only (in combination with vincristine, mercaptopurine, prednisone, oral methotrexate, and intrathecal methotrexate) (Winter 2015; Winter 2018).
T-cell acute lymphoblastic leukemia (T-ALL), T-cell lymphoblastic lymphoma; relapsed/refractory: Children and Adolescents: IV:
Monotherapy: 650 mg/m2/dose on days 1 through 5; repeat cycle every 21 days until transplant, disease progression, or unacceptable toxicity (Zwaan 2017).
Combination therapy: Limited data available: 650 mg/m2/dose for 5 consecutive days (in combination with etoposide and cyclophosphamide) for up to 2 cycles. In the clinical trial, nelarabine was administered either before (days 1 through 5) or 1 to 2 days after other chemotherapy (days 7 or 8 through 11 or 12) (in combination with etoposide and cyclophosphamide) for up to 2 cycles (Commander 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children and Adolescents:
Neurologic toxicity ≥ grade 2: Discontinue treatment.
Hematologic or other (non-neurologic) toxicity: Consider treatment delay.
All patients:
CrCl ≥50 mL/minute: No adjustment necessary
CrCl <50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (although ARA-G clearance is decreased as renal function declines, data is insufficient for a dosing recommendation); monitor closely.
All patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); closely monitor with severe impairment (total bilirubin >3 times ULN).
Refer to adult dosing. Age ≥65 years may be associated with increased neurotoxicity; monitor closely.
Neurologic toxicity ≥ grade 2: Discontinue treatment.
Hematologic or other (non-neurologic) toxicity: Consider treatment delay.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Arranon: 5 mg/mL (50 mL)
Generic: 5 mg/mL (50 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Atriance: 5 mg/mL (50 mL)
IV: Adequate IV hydration and prophylactic antihyperuricemic therapy are recommended to prevent tumor lysis syndrome.
Infuse over 2 hours on days 1, 3, and 5.
Adequate IV hydration and prophylactic antihyperuricemic therapy may be considered to prevent tumor lysis syndrome.
IV: Infuse doses over 1 hour.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
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
Nelarabine may be confused with clofarabine
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (adults: 15%), edema (adults: 11%)
Central nervous system: Fatigue (adults: 50%), drowsiness (adults: 23%; children and adolescents: 7%), dizziness (adults: 21%), hypoesthesia (adults: 17%; children and adolescents: 6%), headache (15% to 17%), paresthesia (adults: 15%; children and adolescents: 4%), peripheral sensory neuropathy (6% to 13%; children and adolescents, grade 3: 6%), pain (adults: 11%)
Endocrine & metabolic: Decreased serum potassium (children and adolescents: 11%)
Gastrointestinal: Nausea (adults: 41%), diarrhea (adults: 22%), vomiting (adults: 22%; children and adolescents: 10%), constipation (adults: 21%)
Hematologic & oncologic: Anemia (95% to 99%; children and adolescents, grade 3: 45%; adults, grade 3: 20%; grades ≥4: 10% to 14%), neutropenia (children and adolescents: 94%; adults: 81%; grade 3: 14% to 17%, children and adolescents, grades ≥4: 62%, adults, grades ≥4: 49%), thrombocytopenia (86% to 88%; adults, grade 3: 37%; children and adolescents, grade 3: 27%; children and adolescents, grades ≥4: 32%; adults, grades ≥4: 22%), leukopenia (children and adolescents: 38%; children and adolescents, grade 3: 14%; children and adolescents, grades ≥4: 7%), febrile neutropenia (adults: 12%; adults, grade 3: 9%; adults, grades ≥4: 1%), petechia (adults: 12%; adults, grade 3: 2%)
Hepatic: Increased serum transaminases (children and adolescents: 12%)
Neuromuscular & skeletal: Asthenia (adults: 17%; children and adolescents: 6%), myalgia (adults: 13%)
Respiratory: Cough (adults: 25%), dyspnea (adults: 20%)
Miscellaneous: Fever (adults: 23%)
1% to 10%:
Cardiovascular: Hypotension (adults: 8%), sinus tachycardia (adults: 8%), chest pain (adults: 5%)
Central nervous system: Ataxia (adults: 9%; children and adolescents: 2%), confusion (adults: 8%), myasthenia (adults: 8%), rigors (adults: 8%), insomnia (adults: 7%), peripheral motor neuropathy (4% to 7%; grade 3: 1% to 2%), abnormal gait (adults: 6%), depression (adults: 6%), impaired consciousness (adults: 6%), seizure (children and adolescents: 6%; adults, grade 3: 1%), peripheral neuropathy (5% to 6%; grade 3: 1% to 2%), noncardiac chest pain (adults: 5%), motor dysfunction (children and adolescents: 4%), neuropathy (adults: 4%), amnesia (adults: 3%), balance impairment (adults: 2%), abnormal sensory symptoms (1% to 2%), aphasia (adults, grade 3: 1%), burning sensation (adults: 1%), cerebral hemorrhage (adults, grade 4: 1%), cranial nerve palsy (third and sixth nerve, children and adolescents: 1%), coma (adults, grade 4: 1%), disturbance in attention (adults: 1%), dysarthria (1%), encephalopathy (children and adolescents, grade 4: 1%), hemiparesis (adults, grade 3: 1%), hydrocephalus (children and adolescents: 1%), hypertonia (children and adolescents, grade 3: 1%), hyporeflexia (1%), intracranial hemorrhage (adults, grade 4: 1%), lethargy (children and adolescents: 1%), leukoencephalopathy (adults, grade 4: 1%), loss of consciousness (adults, grade 3: 1%), mental status changes (children and adolescents: 1%), nerve palsy (adults: 1%), paralysis (children and adolescents: 1%), neuralgia (adults: 1%), sciatica (adults: 1%), speech disturbance (adults: 1%), status epilepticus (children and adolescents: 1%)
Endocrine & metabolic: Decreased serum albumin (children and adolescents: 10%), decreased serum calcium (children and adolescents: 8%), dehydration (adults: 7%), decreased serum glucose (children and adolescents: 6%), decreased serum magnesium (children and adolescents: 6%), hyperglycemia (adults: 6%)
Gastrointestinal: Abdominal pain (adults: 9%), anorexia (adults: 9%), stomatitis (adults: 8%; grade 3: 1%), abdominal distention (adults: 6%), dysgeusia (adults: 3%)
Hepatic: Increased serum bilirubin (children and adolescents: 10%), increased serum aspartate aminotransferase (adults: 6%)
Infection: Infection (5% to 9%)
Neuromuscular & skeletal: Arthralgia (adults: 9%), back pain (adults: 8%), limb pain (adults: 7%), tremor (4% to 5%)
Ophthalmic: Blurred vision (adults: 4%), nystagmus disorder (adults: 1%)
Renal: Increased serum creatinine (children and adolescents: 6%)
Respiratory: Pleural effusion (adults: 10%), epistaxis (adults: 8%), pneumonia (adults: 8%), dyspnea on exertion (adults: 7%), sinusitis (adults: 7%), wheezing (adults: 5%), sinus headache (adults: 1%)
Postmarketing: Demyelinating disease, increased creatine phosphokinase in blood specimen, opportunistic infection, progressive multifocal leukoencephalopathy, rhabdomyolysis, tumor lysis syndrome
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to nelarabine or any component of the formulation.
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).
• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
• 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.
Disease-related concerns:
• 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.
Other warnings/precautions:
• Vaccines: Avoid administration of live vaccines to immunocompromised patients.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: 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. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: 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. Risk D: 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. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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.
Based on its mechanism of action and findings in animal reproduction studies, nelarabine may cause fetal harm if administered during pregnancy.
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 (ESMO [Peccatori 2013]).
It is not known if nelarabine or ara-G are present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
CBC with differential, liver and kidney function. HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). 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.
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.
Distribution: Vss:
Nelarabine: Pediatric patients: 213 ± 358 L/m2; Adults: 197 ± 216 L/m2
Ara-G: Pediatric patients: 33 ± 9.3 L/m2; Adults: 50 ± 24 L/m2
Protein binding: Nelarabine and Ara-G: <25%
Metabolism: 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.
Half-life elimination: Pediatric patients: Nelarabine: 13 minutes, Ara-G: 2 hours; Adults: Nelarabine: 18 minutes, Ara-G: 3.2 hours
Time to peak: Ara-G: Adults: 3 to 25 hours (of day 1)
Excretion: Urine (nelarabine 5% to 10%, Ara-G 20% to 30%)
Clearance: 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)
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.
Geriatric: Reduced renal function in elderly patients may reduce ara-G clearance.
Race: Mean clearance and Vd values tended to be higher in white patients than in black patients (by ~10%). The opposite is true for ara-G; mean apparent clearance and Vd values tended to be lower in white patients than in black patients (by ~15% to 20%).
Solution (Arranon Intravenous)
5 mg/mL (per mL): $17.65
Solution (Nelarabine Intravenous)
5 mg/mL (per mL): $15.86
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