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Nelarabine: Drug information

Nelarabine: Drug information
(For additional information see "Nelarabine: Patient drug information" and see "Nelarabine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Neurologic 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.

Brand Names: US
  • Arranon
Brand Names: Canada
  • Atriance
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Purine Analog)
Dosing: Adult

Note: Adequate hydration and prophylactic antihyperuricemic therapy are recommended to prevent tumor lysis syndrome.

T-cell acute lymphoblastic leukemia/lymphoma, relapsed/refractory

T-cell acute lymphoblastic leukemia/lymphoma, relapsed/refractory: 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.

Dosing: Kidney Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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).

Dosing: Obesity: Adult

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; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Neurologic toxicity ≥ grade 2: Discontinue treatment.

Hematologic or other (non-neurologic) toxicity: Consider treatment delay.

Dosing: Older Adult

Refer to adult dosing. Age ≥65 years may be associated with increased neurotoxicity; monitor closely.

Dosing: Pediatric

(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; newly diagnosed, high risk

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-cell lymphoblastic lymphoma; relapsed/refractory

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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).

Adverse Reactions

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

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to nelarabine or any component of the formulation.

Warnings/Precautions

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.

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Arranon Intravenous)

5 mg/mL (per mL): $19.40

Solution (Nelarabine Intravenous)

5 mg/mL (per mL): $15.84 - $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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Atriance: 5 mg/mL (50 mL)

Administration: Adult

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.

Administration: Pediatric

Adequate IV hydration and prophylactic antihyperuricemic therapy may be considered to prevent tumor lysis syndrome.

IV: Infuse doses over 1 hour.

Hazardous Drugs Handling Considerations

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).

Use: Labeled Indications

T-cell acute lymphoblastic leukemia/lymphoma, relapsed/refractory: Treatment of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma in patients ≥1 year of age following at least 2 chemotherapy regimens

Medication Safety Issues
Sound-alike/look-alike issues:

Nelarabine may be confused with clofarabine

High alert medication:

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.

Metabolism/Transport Effects

None known.

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

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

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

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: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). 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: 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). 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

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). 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

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- 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 Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

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

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. 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 decrease serum concentrations of the active metabolite(s) of Nelarabine. 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 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

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

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

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). 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

Reproductive Considerations

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.

Pregnancy Considerations

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]).

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: 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.

Older adult: Reduced renal 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%).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Atriance;
  • (BE) Belgium: Atriance;
  • (BG) Bulgaria: Atriance;
  • (CH) Switzerland: Atriance;
  • (CZ) Czech Republic: Atriance;
  • (DE) Germany: Atriance;
  • (EE) Estonia: Atriance;
  • (FI) Finland: Atriance;
  • (FR) France: Atriance;
  • (GB) United Kingdom: Atriance;
  • (GR) Greece: Atriance;
  • (HR) Croatia: Atriance;
  • (HU) Hungary: Atriance;
  • (IE) Ireland: Atriance;
  • (IT) Italy: Atriance;
  • (JP) Japan: Arranon G;
  • (LV) Latvia: Atriance;
  • (NL) Netherlands: Atriance;
  • (NO) Norway: Atriance;
  • (NZ) New Zealand: Atriance;
  • (PL) Poland: Atriance;
  • (PT) Portugal: Atriance;
  • (RO) Romania: Atriance;
  • (RU) Russian Federation: Atriance | Atrians;
  • (SE) Sweden: Artiance | Atriance;
  • (SI) Slovenia: Atriance;
  • (SK) Slovakia: Atriance;
  • (TN) Tunisia: Atriance;
  • (TW) Taiwan: Atriance
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Arranon (nelarabine) (prescribing information). East Hanover, NJ: Novartis Pharmaceuticals; July 2019.
  3. Atriance (nelarabine) [product monograph]. Boucherville, Quebec, Canada: Sandoz Canada Inc; November 2022.
  4. Berg SL, Blaney SM, Devidas M, et al, “Phase II Study of Nelarabine (Compound 506U78) in Children and Young Adults With Refractory T-Cell Malignancies: A Report from the Children’s Oncology Group,” J Clin Oncol, 2005, 23(15):3376-82. [PubMed 15908649]
  5. Commander LA, Seif AE, Insogna IG, et al, “Salvage Therapy With Nelarabine, Etoposide, and Cyclophosphamide in Relapsed/Refractory Paediatric T-Cell Lymphoblastic Leukaemia and Lymphoma,” Br J Haematol, 2010, 150(3):345-351. [PubMed 20528871]
  6. DeAngelo DJ, Yu D, Johnson JL, et al, “Nelarabine Induces Complete Remissions in Adults With Relapsed or Refractory T-Lineage Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: Cancer and Leukemia Group B Study 19801,” Blood, 2007, 109(12):5136-42. [PubMed 17344466]
  7. Gandhi V, Plunkett W, Weller S, et al, "Evaluation of the Combination of Nelarabine and Fludarabine in Leukemias: Clinical Response, Pharmacokinetics, and Pharmacodynamics in Leukemia Cells," J Clin Oncol, 2001, 19(8):2142-52. [PubMed 11304766]
  8. Gökbuget N, Basara N, Baurmann H, et al, “High Single-Drug Activity of Nelarabine in Relapsed T-Lymphoblastic Leukemia/Lymphoma Offers Curative Option With Subsequent Stem Cell Transplantation,” Blood, 2011, 118(13):3504-11. [PubMed 21715318]
  9. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  10. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  11. Kaiser J, Krämer I. Physico-chemical stability of nelarabine infusion solutions in EVA infusion bags. EJHP Science. 2011;17(1):7-12. [PubMed Kaiser.1]
  12. Kisor DF, Plunkett W, Kurtzberg J, et al, “Pharmacokinetics of Nelarabine and 9-beta-D-Arabinofuranosyl Guanine in Pediatric and Adult Patients During a Phase I Study of Nelarabine for the Treatment of Refractory Hematologic Malignancies,” J Clin Oncol, 2000, 18(5):995-1003. [PubMed 10694549]
  13. Kurtzberg J, Ernst TJ, Keating MJ, et al, "Phase I Study of 506U78 Administered on a Consecutive 5-Day Schedule in Children and Adults With Refractory Hematologic Malignancies," J Clin Oncol, 2005, 23(15):3396-403. [PubMed 15908652]
  14. Peccatori FA, Azim HA Jr, Orecchia R, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi160-167. [PubMed 23813932]
  15. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed August 27, 2020.
  16. Winter SS, Dunsmore KP, Devidas M, et al. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015;62(7):1176-1183. [PubMed 25755211]
  17. Winter SS, Dunsmore KP, Devidas M, et al. Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization [published correction appeared in: J Clin Oncol. 2019;37(9):761]. J Clin Oncol. 2018;36(29):2926-2934. doi: 10.1200/JCO.2018.77.7250. [PubMed 30138085]
  18. Zwaan CM, Kowalczyk J, Schmitt C, et al. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017;179(2):284-293. [PubMed 28771663]
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