Version July 2025
Severe neurologic adverse reactions have been reported with the use of nelarabine. These adverse 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 adverse 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.
Dosage guidance:
Safety : Adequate hydration and prophylactic antihyperuricemic therapy are recommended prior to and during therapy to prevent tumor lysis syndrome.
T-cell acute lymphoblastic leukemia/lymphoma, relapsed/refractory: IV: 1,500 mg/m2/dose on days 1, 3, and 5; repeat every 21 days; continue until a transplant candidate, until disease progression, unacceptable toxicity, or until no longer benefiting from therapy (Ref).
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; monitor closely for toxicities.
CrCl <50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling, (although ARA-G clearance is decreased as kidney function declines, data is insufficient for a dosing recommendation). The risk for toxicities may be higher in patients with CrCl <50 mL/minute; monitor closely for toxicities.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). The risk for toxicities may be higher in patients with severe impairment (total bilirubin >3 times ULN); monitor closely for toxicities.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2 (Ref).
Hematologic toxicity: Consider treatment delay.
Neurologic toxicity ≥ grade 2: Discontinue treatment.
Other (non-neurologic) toxicity: Consider treatment delay.
Refer to adult dosing. Age ≥65 years may be associated with increased neurotoxicity; monitor closely.
(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) (Ref).
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) (Ref).
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) (Ref).
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 (Ref).
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 (Ref).
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).
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.
• Neurotoxicity: Severe, life-threatening, or fatal CNS toxicities, including mental status changes, severe somnolence, seizures, and peripheral neuropathy (ranging from numbness and paresthesias to motor weakness and paralysis), have been reported. 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). Risk of neurotoxicity may be increased in patients with concurrent or previous intrathecal chemotherapy or prior craniospinal irradiation. 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, driving).
• Tumor lysis syndrome: Tumor lysis syndrome may occur as a consequence of leukemia treatment. May lead to life-threatening acute kidney failure.
Special populations:
• Older adults: In an exploratory analysis of nelarabine-treated patients, increasing age, notably ≥65 years of age, appears to be associated with increased rates of neurotoxicity.
Other warnings/precautions:
• Vaccines: Avoid administration of live vaccines to immunocompromised patients.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 5 mg/mL (50 mL)
Solution, Intravenous [preservative free]:
Arranon: 5 mg/mL (50 mL)
Generic: 5 mg/mL (50 mL)
Yes
Solution (Arranon Intravenous)
5 mg/mL (per mL): $19.40
Solution (Nelarabine Intravenous)
5 mg/mL (per mL): $8.75 - $15.86
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 2024 [table 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 2023; NIOSH 2024; USP-NF 2020).
T-cell acute lymphoblastic leukemia/lymphoma, relapsed/refractory: Treatment of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma in adult and pediatric patients ≥1 year of age following treatment with at least 2 chemotherapy regimens.
Nelarabine may be confused with cladribine, clofarabine, cytarabine.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects 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
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects 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 decrease therapeutic effects 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
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects 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 decrease active metabolite exposure of Nelarabine. Risk X: Avoid
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects 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
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during nelarabine therapy. Patients (including those who have had vasectomies) with partners who could become pregnant 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, in utero exposure to nelarabine may cause fetal harm.
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 (regularly), liver and kidney function. Verify pregnancy status prior to therapy initiation (in patients who could become pregnant). Monitor closely and frequently 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 patients with kidney or hepatic dysfunction closely for toxicities. Monitor for signs and symptoms of tumor lysis syndrome; monitor hydration status.
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.
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)
Altered kidney function: Clearance of Ara-G is reduced 15% in patients with mild kidney impairment (CrCl 50 to 80 mL/minute) and 40% in patients with moderate kidney impairment (CrCl <50 mL/minute), compared to patients with normal kidney function.
Older adult: Reduced kidney function in elderly patients may reduce ara-G clearance.
Race/ethnicity: 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%).
