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    Purine Analogs

    BOXED WARNING

    Driving or operating machinery, geriatric, neurologic events, neurotoxicity, radiation therapy

    Serious neurologic events (e.g., coma, seizures, and paralysis) have been reported with nelarabine use; some cases were irreversible. Monitor patients for signs or symptoms of neurotoxicity during therapy and for at least 24 hours after the completion of treatment. Discontinue nelarabine and provide supportive care in patients who develop grade 2 or higher neurologic adverse reactions. Patients who have received prior intrathecal chemotherapy or craniospinal radiation therapy and geriatric patients 65 years of age and older may be at increased risk of developing neurologic adverse reactions. Because nelarabine may cause extreme drowsiness/somnolence during and for several days after therapy, patients should avoid driving or operating machinery during this time.[44107]

    DEA CLASS

    Rx

    DESCRIPTION

    Cytotoxic purine analog
    Used in relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma
    Severe neurologic adverse reactions have been reported

    COMMON BRAND NAMES

    Arranon

    HOW SUPPLIED

    Arranon/Nelarabine Intravenous Inj Sol: 1mL, 5mg

    DOSAGE & INDICATIONS

    For the treatment of T-cell leukemia/lymphoma.
    NOTE: The FDA has designated nelarabine as an orphan drug for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma.
    For the treatment of relapsed or refractory T-cell acute lymphoblastic leukemia (ALL) or T-cell lymphoblastic lymphoma following at least 2 prior chemotherapy regimens.
    Intravenous dosage
    Adults

    1,500 mg/m2 IV over 2 hours on days 1, 3, and 5 repeated every 21 days; therapy was continued until disease progression, unacceptable toxicity, or bone marrow transplant in clinical trials. Therapy delay or discontinuation may be necessary in patients who develop toxicity. In a multicenter, phase 2 study (n = 39), treatment with nelarabine (median duration of therapy, 56 days; range, 10 to 136 days) led to a complete response (CR) rate of 21% (CR plus CR with incomplete hematologic recovery) in a subpopulation of patients (n = 28; median age, 34 years; range, 16 to 64 years) with relapsed or refractory T-cell ALL or lymphoblastic lymphoma who received at least 2 prior regimens; the time to CR ranged from 2.9 to 11.7 weeks. Additionally, the median overall survival time was 20.6 weeks in this study.

    Children and Adolescents

    650 mg/m2 IV over 1 hour daily on days 1, 2, 3, 4, and 5 repeated every 21 days; therapy was continued until disease progression, unacceptable toxicity, or bone marrow transplant in clinical trials. Therapy delay or discontinuation may be necessary in patients who develop toxicity. In a multicenter, phase 2 study (n = 84), treatment with nelarabine (median duration of therapy, 46 days; range, 7 to more than 129 days) led to a complete response (CR) rate of 23% (CR plus CR with incomplete hematologic recovery) in a subpopulation of patients (n = 39; median age, 11.9 years; range, 2.5 to 21.7 years) with relapsed or refractory T-cell ALL or lymphoblastic lymphoma who received at least 2 prior regimens. The median time to CR was 3.4 weeks and the duration of CR ranged from 3.3 to 9.3 weeks. Additionally, the median overall survival time was 13.1 weeks in this study.

    For the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL)†.
    Intravenous dosage
    Adults

    Multiple regimens have been studied. In a phase 1 study of 24 patients with relapsed or refractory CLL and 11 patients with relapsed or refractory T-cell prolymphocytic leukemia, 20 to 50 mg/kg IV over 1 hour daily for 5 days per cycle or 1,500 to 2,900 mg/m2 IV on days 1, 3, and 5 (repeated every 21 to 28 days) led to overall response rates (ORR) of 20% (complete response (CR), 0%) and 15% (CR, 5%), respectively; also, 1,200 mg/m2 IV over 2 hours on days 1, 3, and 5 repeated every 21 to 28 days) in combination with fludarabine resulted in an ORR of 63% (CR, 13%) in the same study. Most patients (70%) in this study had fludarabine refractory disease. In another phase 1 study, 3 of 10 patients with refractory T- or B-cell CLL had a partial response (no CR) following treatment with nelarabine 5 to 75 mg/kg IV over 1 hour daily for 5 days per cycle.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1,500 mg/m2 IV on days 1, 3, and 5.

    Geriatric

    1,500 mg/m2 IV on days 1, 3, and 5.

    Adolescents

    650 mg/m2/day IV for 5 days.

    Children

    650 mg/m2/day IV for 5 days.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustment is needed.

    Renal Impairment

    No dosage adjustment is required for patients with a creatinine clearance (CrCl) of 50 mL/min or greater. There are insufficient data to support a dose recommendation for patients who have a CrCl less than 50 mL/min.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
    Emetic Risk
    Low
    Administer routine antiemetic prophylaxis prior to treatment.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Transfer the appropriate amount of nelarabine to a polyvinylchloride (PVC) infusion bag or glass container; do not dilute prior to administration.
    Storage: Nelarabine is stable in polyvinylchloride (PVC) bags or glass containers for up to 8 hours at up to 30 degrees C.
    Intravenous infusion:
    Administer as an IV infusion over 2 hours in adults and 1 hour in pediatric patients.

    STORAGE

    Arranon:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Driving or operating machinery, geriatric, neurologic events, neurotoxicity, radiation therapy

    Serious neurologic events (e.g., coma, seizures, and paralysis) have been reported with nelarabine use; some cases were irreversible. Monitor patients for signs or symptoms of neurotoxicity during therapy and for at least 24 hours after the completion of treatment. Discontinue nelarabine and provide supportive care in patients who develop grade 2 or higher neurologic adverse reactions. Patients who have received prior intrathecal chemotherapy or craniospinal radiation therapy and geriatric patients 65 years of age and older may be at increased risk of developing neurologic adverse reactions. Because nelarabine may cause extreme drowsiness/somnolence during and for several days after therapy, patients should avoid driving or operating machinery during this time.[44107]

    Hyperuricemia, tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) has been reported with nelarabine use. Administer IV hydration and other prophylactic measures such as urine alkalinization and anti-uric acid medications (e.g., allopurinol) in patients at risk for TLS or hyperuricemia. Monitor patients for signs and symptoms of TLS.

    Hepatic disease

    The risk of nelarabine-related adverse reactions may be higher in patients with severe hepatic impairment (bilirubin level greater than 3-times the upper limit of normal); closely monitor patients with hepatic disease for signs or symptoms of toxicity.

    Renal disease, renal impairment

    The risk of nelarabine-related adverse reactions may be higher in patients with moderate (creatinine clearance (CrCl), 30 to 50 mL/min) or severe (CrCl less than 30 mL/min) renal impairment; closely monitor these patients for signs or symptoms of toxicity. Monitor renal function in patients with renal disease.

    Vaccination

    Vaccination with live viral vaccines should be avoided in immunocompromised patients who are receiving nelarabine.

    Anemia, children, neutropenia, thrombocytopenia

    Hematologic toxicity (e.g., anemia, neutropenia, thrombocytopenia) has been reported with nelarabine use. Children may be at increased risk of developing hematologic toxicity. Monitor complete blood counts including platelets at regular intervals. A delay in nelarabine therapy may be necessary in patients who develop severe hematologic toxicity.

    Pregnancy

    Nelarabine may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Advise females of reproductive potential to avoid pregnancy while taking nelarabine. Discuss the potential hazard to the fetus if nelarabine is used during pregnancy or if a patient becomes pregnant while taking this drug. Drug-associated risks to the fetus are unknown based on limited available data regarding nelarabine use in pregnant women. Embryo-fetal toxicities including cleft palate, absent gall bladder, absent accessory lung lobes, fused or extra sternebrae, and delayed ossification were observed in offspring of pregnant rabbits who received nelarabine doses resulting in drug exposures that were up to 2-times the recommended human exposure. Additionally, an increased rate of malformations, anomalies, and variations occurred in the offspring of pregnant rabbits who received nelarabine at doses that were about 25% of the recommended human dose.

    Contraception requirements, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during nelarabine therapy. Pregnancy testing prior to starting nelarabine is recommended for females of reproductive potential. These patients should use effective contraceptive methods during nelarabine therapy. Advise women to contact their healthcare provider if pregnancy is suspected or confirmed. Women who become pregnant while receiving nelarabine should be apprised of the potential hazard to the fetus. Due to a potential for male-mediated teratogenicity, male patients (including men who have had a vasectomy) with female partners of reproductive potential should use effective contraception (i.e., condoms) during nelarabine therapy and for 3 months after the last dose.

    Breast-feeding

    It is not known if nelarabine or Ara-G are secreted in human milk or they have effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions (e.g., neurologic adverse reactions) in nursing infants, women should discontinue breast-feeding during nelarabine therapy.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 63.0-79.0
    thrombocytopenia / Delayed / 59.0-59.0
    anemia / Delayed / 34.0-55.0
    leukopenia / Delayed / 21.0-21.0
    neurotoxicity / Early / 15.0-19.0
    fatigue / Early / 12.0-12.0
    pleural effusion / Delayed / 10.0-10.0
    hyperbilirubinemia / Delayed / 9.0-9.0
    seizures / Delayed / 1.0-6.0
    peripheral neuropathy / Delayed / 0-6.0
    headache / Early / 1.0-6.0
    hypoalbuminemia / Delayed / 6.0-6.0
    hypokalemia / Delayed / 6.0-6.0
    dyspnea / Early / 6.0-6.0
    weakness / Early / 5.0-5.0
    fever / Early / 5.0-5.0
    hypoesthesia / Delayed / 2.0-4.0
    dehydration / Delayed / 4.0-4.0
    elevated hepatic enzymes / Delayed / 2.0-4.0
    hypoglycemia / Early / 4.0-4.0
    infection / Delayed / 3.0-3.0
    ataxia / Delayed / 1.0-2.0
    drowsiness / Early / 0-2.0
    hypocalcemia / Delayed / 2.0-2.0
    hypomagnesemia / Delayed / 2.0-2.0
    hypotension / Rapid / 2.0-2.0
    confusion / Early / 2.0-2.0
    petechiae / Delayed / 2.0-2.0
    hydrocephalus / Delayed / 1.0-1.0
    intracranial bleeding / Delayed / 1.0-1.0
    coma / Early / 1.0-1.0
    leukoencephalopathy / Delayed / 1.0-1.0
    paresthesias / Delayed / 0-1.0
    muscle paralysis / Delayed / 1.0-1.0
    Guillain-Barre syndrome / Delayed / 0-1.0
    constipation / Delayed / 1.0-1.0
    diarrhea / Early / 1.0-1.0
    vomiting / Early / 0-1.0
    stomatitis / Delayed / 1.0-1.0
    abdominal pain / Early / 1.0-1.0
    hyperglycemia / Delayed / 1.0-1.0
    sinus tachycardia / Rapid / 1.0-1.0
    pneumothorax / Early / 0-1.0
    sinusitis / Delayed / 1.0-1.0
    arthralgia / Delayed / 1.0-1.0
    myalgia / Early / 1.0-1.0
    rhabdomyolysis / Delayed / 0-1.0
    depression / Delayed / 1.0-1.0
    asthenia / Delayed / 1.0-1.0
    tumor lysis syndrome (TLS) / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 15.0-15.0
    edema / Delayed / 11.0-11.0
    chest pain (unspecified) / Early / 5.0-5.0
    wheezing / Rapid / 5.0-5.0
    blurred vision / Early / 4.0-4.0
    amnesia / Delayed / 3.0-3.0
    dysarthria / Delayed / 1.0-1.0
    aphasia / Delayed / 1.0-1.0
    hypertonia / Delayed / 1.0-1.0
    encephalopathy / Delayed / 1.0-1.0
    nystagmus / Delayed / 1.0-1.0
    paresis / Delayed / 1.0-1.0
    neuropathic pain / Delayed / 1.0-1.0
    hyperuricemia / Delayed / Incidence not known

    Mild

    nausea / Early / 41.0-41.0
    cough / Delayed / 25.0-25.0
    dizziness / Early / 21.0-21.0
    anorexia / Delayed / 9.0-9.0
    epistaxis / Delayed / 8.0-8.0
    back pain / Delayed / 8.0-8.0
    chills / Rapid / 8.0-8.0
    insomnia / Early / 7.0-7.0
    tremor / Early / 4.0-5.0
    dysgeusia / Early / 3.0-3.0
    lethargy / Early / 1.0-1.0
    hyporeflexia / Delayed / 1.0-1.0
    dysesthesia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abciximab: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Anagrelide: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Anticoagulants: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
    Aspirin, ASA; Dipyridamole: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Celecoxib: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cilostazol: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Clopidogrel: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Diclofenac: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diflunisal: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Dipyridamole: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Eptifibatide: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Etodolac: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    Fenoprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Flurbiprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Ibuprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Indomethacin: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Ketoprofen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ketorolac: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefenamic Acid: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meloxicam: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Nabumetone: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Oxaprozin: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Pegfilgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Piroxicam: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Platelet Inhibitors: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Prasugrel: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Rofecoxib: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Rubella Virus Vaccine Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Sulindac: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Ticagrelor: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Ticlopidine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Tirofiban: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Tolmetin: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Valdecoxib: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Vorapaxar: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

    PREGNANCY AND LACTATION

    Pregnancy

    Nelarabine may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Advise females of reproductive potential to avoid pregnancy while taking nelarabine. Discuss the potential hazard to the fetus if nelarabine is used during pregnancy or if a patient becomes pregnant while taking this drug. Drug-associated risks to the fetus are unknown based on limited available data regarding nelarabine use in pregnant women. Embryo-fetal toxicities including cleft palate, absent gall bladder, absent accessory lung lobes, fused or extra sternebrae, and delayed ossification were observed in offspring of pregnant rabbits who received nelarabine doses resulting in drug exposures that were up to 2-times the recommended human exposure. Additionally, an increased rate of malformations, anomalies, and variations occurred in the offspring of pregnant rabbits who received nelarabine at doses that were about 25% of the recommended human dose.

    Counsel patients about the reproductive risk and contraception requirements during nelarabine therapy. Pregnancy testing prior to starting nelarabine is recommended for females of reproductive potential. These patients should use effective contraceptive methods during nelarabine therapy. Advise women to contact their healthcare provider if pregnancy is suspected or confirmed. Women who become pregnant while receiving nelarabine should be apprised of the potential hazard to the fetus. Due to a potential for male-mediated teratogenicity, male patients (including men who have had a vasectomy) with female partners of reproductive potential should use effective contraception (i.e., condoms) during nelarabine therapy and for 3 months after the last dose.

    MECHANISM OF ACTION

    Nelarabine is as a prodrug for deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (Ara-G), which acts as a cytotoxic agent and inhibits DNA synthesis. Upon administration, nelarabine, is rapidly demethylated by adenosine deaminase (ADA) to Ara-G. Ara-G is transported into cells by nucleoside transporters. Once inside the cell, Ara-G is mono-phosphorylated, and converted to the active 5'-triphosphate, Ara-GTP. Accumulation of Ara-GTP in leukemic blasts allows for incorporation into DNA. Incorporation into DNA halts DNA synthesis and causes cell death. Other mechanisms of action include inhibition of RNA synthesis and ribonucleotide reductase inhibition. Ara-G is thought to be more toxic to T-lymphoblasts than other blast cells due to enhanced accumulation of Ara-GTP in T-cells and increased elimination of Ara-GTP from B-cells. The clinical efficacy of nelarabine is associated with the intracellular concentrations of Ara-G.

    PHARMACOKINETICS

    Nelarabine is administered as an intravenously. It is a prodrug of 9-beta-D-arabinofuranosylguanine (Ara-G). Nelarabine and Ara-G are minimally bound to plasma proteins (less than 25%) in vitro; binding is independent for concentrations up to 600 micromolar. The mean steady-state volume of distribution values are 197 (+/- 216) and 50 (+/- 24) L/m2. Nelarabine is metabolized mainly by O-demethylation via adenosine deaminase to form Ara-G; some nelarabine is hydrolyzed to methylguanine which is then O-demethylated to form guanine. Ara-G undergoes hydrolysis to form guanine. Guanine is N-deaminated to form xanthine which is oxidized to uric acid. Following nelarabine doses of 199 to 2,900 mg/m2 in 66 adult patients, the mean clearance of nelarabine and Ara-G were 197 (+/- 189) and 10.5 (+/- 4.5) L/hour/m2 on day 1; the mean terminal half-lives were 18 minutes and 3.2 hours, respectively. The mean 24 hour renal excretion of nelarabine and Ara-G were 6.6% (+/- 4.7%) and 27% (+/- 15%) of the administered dose on day 1 in 28 adult patients; the renal clearance values were 24 (+/- 23) and 6.2 (+/- 5) L/hour, respectively, in 21 patients.
    Affected cytochrome P450 isoenzymes and drug transporters: none
    Nelarabine and Ara-G did not significantly inhibit the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in vitro at concentrations up to 100 micromolar.

    Intravenous Route

    Following nelarabine 1,500 mg/m2 IV administered over 2 hours, the mean peak plasma concentrations (Cmax) for nelarabine and Ara-G were 5 (+/- 3) and 31.4 (+/- 5.6) mcg/mL, respectively, in adult patients with refractory leukemia or lymphoma. The mean AUC values were 4.4 (+/- 2.2) and 162 (+/- 49) mcg X hour/mL for nelarabine and Ara-G, respectively. Nelarabine does accumulate after multiple doses.