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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(sye TARE a been)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Remission induction in acute myeloid leukemia (AML), treatment of acute lymphocytic leukemia (ALL) and chronic myelocytic leukemia (CML; blast phase); prophylaxis and treatment of meningeal leukemia
Use: Unlabeled/Investigational
Postinduction, postremission consolidation, and salvage treatment of AML; treatment of primary central nervous system (CNS) lymphoma; treatment of relapsed or refractory Hodgkin's lymphoma; treatment of non-Hodgkin's lymphomas (NHL)
Pregnancy Risk Factor
D
Pregnancy Considerations
Cytarabine is teratogenic in animal studies. Limb and ear defects have been noted in case reports when cytarabine has been used during pregnancy. The following have also been noted in the neonate: Pancytopenia, WBC depression, electrolyte abnormalities, prematurity, low birth weight, decreased hematocrit or platelets. Risk to the fetus is decreased if therapy is avoided during the 1st trimester; however, women of childbearing potential should be advised of the potential risks.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended.
Contraindications
Hypersensitivity to cytarabine or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Myelosuppression: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Cytarabine syndrome: Characterized by fever, myalgia, bone pain, chest pain, maculopapular rash, conjunctivitis, and malaise, cytarabine syndrome may occur 6-12 hours following administration; may be managed with corticosteroids.
• Myelosuppression: [U.S. Boxed Warning]: Potent myelosuppressive agent; use with caution in patients with prior bone marrow suppression; monitor for signs of febrile neutropenia.
• Pancreatitis: There have been reports of acute pancreatitis in patients receiving continuous infusion and in patients previously treated with L-asparaginase.
• Tumor lysis syndrome: With high dose therapy, tumor lysis syndrome and subsequent hyperuricemia may occur; consider allopurinol and hydrate accordingly.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; may be at higher risk for CNS toxicities and dosage adjustments may be required.
• Renal impairment: Use with caution in patients with impaired renal function (high dose cytarabine); may be at higher risk for CNS toxicities and dosage adjustments may be required.
Concurrent drug therapy issues:
• Cyclophosphamide: There have been case reports of fatal cardiomyopathy when high-dose cytarabine was used in combination with cyclophosphamide as a preparation regimen for transplantation.
Dosage form specific issues:
• Benzyl alcohol: Some products may contain benzyl alcohol; do not use products containing benzyl alcohol or products reconstituted with bacteriostatic diluent intrathecally or for high-dose cytarabine regimens.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• High dose treatment: High dose regimens have been associated with GI, CNS, pulmonary, ocular (prophylaxis with ophthalmic corticosteroids is recommended) toxicities, and cardiomyopathy. Neurotoxicity associated with high-dose treatment may present as acute cerebellar toxicity or may be severe with seizure and/or coma; may be delayed, occurring up to 3-8 days after treatment has begun; possibly irreversible. Risk factors for neurotoxicity include cumulative cytarabine dose, prior CNS disease and renal impairment (incidence may be up to 55% in patients with renal impairment).
• Intrathecal safety: When used for intrathecal administration, should not be prepared during the preparation of any other agents. After preparation, store intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only. Delivery of intrathecal medications to the patient should only be with other medications intended for administration into the central nervous system (Jacobson, 2009).
Adverse Reactions
Note: Frequency not defined.
Frequent:
Central nervous system: Fever
Dermatologic: Rash
Gastrointestinal: Anal inflammation, anal ulceration, anorexia, diarrhea, mucositis, nausea, vomiting
Hematologic: Myelosuppression, neutropenia (onset: 1-7 days; nadir [biphasic]: 7-9 days and at 15-24 days; recovery [biphasic]: 9-12 and at 24-34 days), thrombocytopenia (onset: 5 days; nadir: 12-15 days; recovery 15-25 days), anemia, bleeding, leukopenia, megaloblastosis, reticulocytes decreased
Hepatic: Hepatic dysfunction, transaminases increased (acute)
Local: Thrombophlebitis
Less frequent:
Cardiovascular: Chest pain, pericarditis
Central nervous system: Dizziness, headache, neural toxicity, neuritis
Dermatologic: Alopecia, pruritus, skin freckling, skin ulceration, urticaria
Gastrointestinal: Abdominal pain, bowel necrosis, esophageal ulceration, esophagitis, pancreatitis, sore throat
Genitourinary: Urinary retention
Hepatic: Jaundice
Local: Injection site cellulitis
Ocular: Conjunctivitis
Renal: Renal dysfunction
Respiratory: Dyspnea
Miscellaneous: Allergic edema, anaphylaxis, sepsis
Infrequent and/or case reports: Acute respiratory distress syndrome, amylase increased, angina, aseptic meningitis, cardiopulmonary arrest (acute), cerebral dysfunction, cytarabine syndrome (bone pain, chest pain, conjunctivitis, fever, maculopapular rash, malaise, myalgia); exanthematous pustulosis, hyperuricemia, injection site inflammation (SubQ injection), injection site pain (SubQ injection), interstitial pneumonitis, lipase increased, pancreatitis, paralysis (intrathecal and I.V. combination therapy), reversible posterior leukoencephalopathy syndrome (RPLS), rhabdomyolysis, toxic megacolon, veno-occlusive liver disease
Adverse events associated with high-dose cytarabine (CNS, gastrointestinal, ocular, and pulmonary toxicities are more common with high-dose regimens):
Cardiovascular: Cardiomegaly, cardiomyopathy (in combination with cyclophosphamide)
Central nervous system: Coma, neurotoxicity (dose-related, cerebellar toxicity may occur in patients receiving high-dose cytarabine [>36-48 g/m2/cycle]; incidence may up to 55% in patients with renal impairment), personality change, somnolence
Dermatologic: Alopecia (complete), desquamation, rash (severe)
Gastrointestinal: Gastrointestinal ulcer, peritonitis, pneumatosis cystoides intestinalis
Hepatic: Hyperbilirubinemia, liver abscess, liver damage, necrotizing colitis
Neuromuscular & skeletal: Peripheral neuropathy (motor and sensory)
Ocular: Corneal toxicity, hemorrhagic conjunctivitis
Respiratory: Pulmonary edema, syndrome of sudden respiratory distress
Miscellaneous: Sepsis
Adverse events associated with intrathecal cytarabine administration:
Central nervous system: Accessory nerve paralysis, fever, necrotizing leukoencephalopathy (with concurrent cranial irradiation, I.T. methotrexate, and I.T. hydrocortisone), neurotoxicity, paraplegia
Gastrointestinal: Dysphagia, nausea, vomiting
Ocular: Blindness (with concurrent systemic chemotherapy and cranial irradiation), diplopia
Respiratory: Cough, hoarseness
Miscellaneous: Aphonia
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Cardiac Glycosides: Antineoplastic Agents may decrease the absorption of Cardiac Glycosides. This may only affect digoxin tablets. Exceptions: Digitoxin. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Flucytosine: Cytarabine may diminish the therapeutic effect of Flucytosine. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Storage
Store intact vials of powder for injection at room temperature of 20°C to 25°C (68°F to 77°F); store intact vials of solution at room temperature of 15°C to 30°C (59°F to 86°F).
I.V.:
Powder for reconstitution: Reconstituted solutions should be stored at room temperature and used within 48 hours.
For I.V. infusion: Solutions for I.V. infusion diluted in D5W or NS are stable for 7 days at room temperature, although the manufacturer recommends administration as soon as possible after preparation.
Intrathecal: Administer as soon as possible after preparation. After preparation, store intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only.
Reconstitution
Use appropriate precautions for handling and disposal. Note: Solutions containing bacteriostatic agents may be used for SubQ and standard-dose (100-200 mg/m2) I.V. cytarabine preparations, but should not be used for the preparation of either intrathecal doses or high-dose I.V. therapies.
I.V.:
Powder for reconstitution: Reconstitute with bacteriostatic water for injection (for standard-dose).
For I.V. infusion: Further dilute in 250-1000 mL 0.9% NaCl or D5W.
Intrathecal: Powder for reconstitution: Reconstitute with preservative free sodium chloride 0.9%; may further dilute to preferred final volume (volume generally based on institution or practitioner preference; may be up to 12 mL) with Elliott's B solution, sodium chloride 0.9% or lactated Ringer's. Intrathecal medications should not be prepared during the preparation of any other agents.
Intrathecal triple therapy (ITT): Cytarabine 30-50 mg with hydrocortisone sodium succinate 15-25 mg and methotrexate 12 mg; compatible together for up to 24 hours in a syringe; however, should be administered administer as soon as possible after preparation because intrathecal preparations are preservative free
Compatibility
Stable in D5LR, D51/4NS, D5NS, D10NS, D5W, LR, NS.
Y-site administration: Compatible: Amifostine, amsacrine, anidulafungin, aztreonam, cefepime, chlorpromazine, cimetidine, cladribine, dexamethasone sodium phosphate, diphenhydramine, doxorubicin liposome, droperidol, etoposide phosphate, famotidine, filgrastim, fludarabine, furosemide, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, idarubicin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone sodium succinate, metoclopramide, morphine, ondansetron, paclitaxel, pemetrexed, piperacillin/tazobactam, prochlorperazine edisylate, promethazine, propofol, ranitidine, sargramostim, sodium bicarbonate, teniposide, thiotepa, vinorelbine. Incompatible Allopurinol, amphotericin B cholesteryl sulfate complex, gallium nitrate, ganciclovir.
Compatibility in syringe: Compatible: Intrathecal triple therapy (ITT): Cytarabine 30-50 mg with hydrocortisone sodium succinate 15-25 mg and methotrexate 12 mg
Mechanism of Action
Inhibits DNA synthesis. Cytosine gains entry into cells by a carrier process, and then must be converted to its active compound, aracytidine triphosphate. Cytosine is a pyrimidine analog and is incorporated into DNA; however, the primary action is inhibition of DNA polymerase resulting in decreased DNA synthesis and repair. The degree of cytotoxicity correlates linearly with incorporation into DNA; therefore, incorporation into the DNA is responsible for drug activity and toxicity. Cytarabine is specific for the S phase of the cell cycle (blocks progression from the G1 to the S phase).
Pharmacodynamics/Kinetics
Distribution: Vd: Total body water; widely and rapidly since it enters the cells readily; crosses blood-brain barrier with CSF levels of 40% to 50% of plasma level
Metabolism: Primarily hepatic; metabolized by deoxycytidine kinase and other nucleotide kinases to aracytidine triphosphate (active); about 86% to 96% of dose is metabolized to inactive uracil arabinoside (ARA-U); intrathecal administration results in little conversion to ARA-U due to the low levels of deaminase in the cerebral spinal fluid
Half-life elimination: I.V.: Initial: 7-20 minutes; Terminal: 1-3 hours; I.T.: 2-6 hours
Time to peak, plasma: SubQ: 20-60 minutes
Excretion: Urine (~80%; 90% as metabolite ARA-U) within 24 hours
Dosage
Details concerning dosing in combination regimens should also be consulted. Children and Adults:
AML remission induction: I.V.: Standard-dose (provided in the FDA-approved labeling): 100 mg/m2/day continuous infusion for 7 days or 100 mg/m2/dose continuous infusion every 12 hours for 7 days
Remission maintenance (unlabeled use):
I.V.: 70-200 mg/m2/day for 2-5 days at monthly intervals
SubQ: 1-1.5 mg/kg single dose for maintenance at 1- to 4-week intervals
High-dose therapies (unlabeled use): I.V.:
Doses of 1-3 g/m2 have been used for refractory or secondary leukemias or refractory non-Hodgkin's lymphoma.
Doses of 1-3 g/m2 every 12 hours for up to 12 doses have been used for leukemia
Bone marrow transplant (unlabeled use): I.V.: 1.5 g/m2 continuous infusion over 48 hours
Meningeal leukemia: I.T.: Dosing provided in the FDA-approved labeling: Usual dose 30 mg/m2 every 4 days; range: 5-75 mg/m2 once daily for 4 days or once every 4 days until CNS findings normalize, followed by 1 additional treatment. Note: Optimal intrathecal chemotherapy dosing should be based on age rather than on body surface area (BSA); CSF volume correlates with age and not to BSA (Bleyer, 1983; Kerr, 2001).
Children: Age-based dosing (unlabeled dosing): I.T.:
CNS prophylaxis:
<1 year: 20 mg per dose
1-2 years: 30 mg per dose
2-3 years: 50 mg per dose
≥3 years: 70 mg per dose
ALL CNS prophylaxis, age-specific doses from literature:
Administer on day 0 of induction therapy (Gaynon, 1993):
1-2 years: 30 mg per dose
2-3 years: 50 mg per dose
≥3 years: 70 mg per dose
Administer as part of intrathecal triple therapy (ITT) on days 1 and 15 of induction therapy; days 1, 15, 50, and 64 (standard risk patients) or days 1, 15, 29, and 43 (high-risk patients) during consolidation therapy; day 1 of reinduction therapy, and during maintenance therapy (very high-risk patients receive on days 1, 22, 45, and 59 of induction, days 8, 22, 36, and 50 of consolidation therapy, days 8 and 38 of reinduction therapy, and during maintenance) (Lin, 2007):
<1 year: 18 mg per dose
1-2 years: 24 mg per dose
2-3 years: 30 mg per dose
≥3 years: 36 mg per dose
Administer on day 0 of induction therapy, then as part of ITT on days 7, 14, and 21 during consolidation therapy; as part of ITT on days 0, 28, and 35 for 2 cycles of delayed intensification therapy, and then maintenance treatment as part of ITT on day 0 every 12 weeks for 38 months (boys) or 26 months (girls) from initial induction treatment (Matloub, 2006):
<2 years: 16 mg per dose
2-3 years: 20 mg per dose
≥3 years: 24-30 mg per dose
Administer on day 15 of induction therapy, days 1 and 15 of reinduction phase; and day 1 of cycle 2 of maintenance 1A phase (Pieters, 2007):
<1 year: 15 mg per dose
≥1 year: 20 mg per dose
Treatment, CNS leukemia (ALL): I.T.: Children: Administer as part of ITT weekly until CSF remission, then every 4 weeks throughout continuation treatment (Lin, 2007):
<1 year: 18 mg per dose
1-2 years: 24 mg per dose
2-3 years: 30 mg per dose
≥3 years: 36 mg per dose
Adult (intrathecal unlabeled uses or doses): I.T.:
CNS prophylaxis (ALL): 100 mg weekly for 8 doses, then every 2 weeks for 8 doses, then monthly for 6 doses (high-risk patients) or 100 mg on day 7 or 8 with each chemotherapy cycle for 4 doses (low risk patients) or 16 doses (high-risk patients) (Cortes, 1995)
or as part of ITT: 40 mg days 0 and 14 during induction, days 1, 4, 8, and 11 during CNS therapy phase, every 18 weeks during intensification and maintenance phases (Storring, 2009)
CNS prophylaxis (APL, as part of ITT): 50 mg per dose; administer 1 dose prior to consolidation and 2 doses during each of 2 consolidation phases (total of 5 doses) (Ades, 2006; Ades, 2008)
CNS leukemia treatment (ALL, as part of ITT): 40 mg twice weekly until CSF cleared (Storring, 2009)
CNS lymphoma treatment: 50 mg twice a week for 4 weeks, then weekly for 4-8 weeks, then every other week for 4 weeks, then every 4 weeks for 4 doses (Glantz, 1999)
Leptomeningeal metastases treatment: 50 mg twice a week for 4 weeks, then weekly for 4 weeks then monthly for 4 doses (NCCN CNS cancer guidelines v.1.2010) or 40-60 mg per dose (DeAngelis, 2005)
Dosage adjustment in renal impairment: The FDA-approved labeling does not contain renal dosing adjustment guidelines; the following guidelines have been used by some clinicians:
Aronoff, 2007 (Cytarabine 100-200 mg/m2): Children and Adults: No adjustment necessary
Kintzel, 1995 (High-dose cytarabine 1-3 g/m2):
Clcr 46-60 mL/minute: Administer 60% of dose
Clcr 31-45 mL/minute: Administer 50% of dose
Clcr <30 mL/minute: Consider use of alternative drug
Smith, 1997 (High-dose cytarabine ≥2 g/m2/dose):
Serum creatinine 1.5-1.9 mg/dL or increase (from baseline) of 0.5-1.2 mg/dL: Reduce dose to 1 g/m2/dose
Serum creatinine ≥2 mg/dL or increase (from baseline) of >1.2 mg/dL: Reduce dose to 0.1 g/m2/day as a continuous infusion
Dosage adjustment in hepatic impairment: Dose may need to be adjusted in patients with liver failure since cytarabine is partially detoxified in the liver. The FDA-approved labeling does not contain hepatic dosing adjustment guidelines; the following guideline has been used by some clinicians:
Floyd, 2006: Transaminases (any elevation): Administer 50% of dose; may increase subsequent doses in the absence of toxicities
Koren, 1992 (dose level not specified): Bilirubin >2 mg/dL: Administer 50% of dose; may increase subsequent doses in the absence of toxicities
Dosage: Combination Regimens
Brain tumors: 8 in 1 (Brain Tumors)
Leukemia, acute lymphocytic:
Hyper-CVAD + Imatinib
Hyper-CVAD (Leukemia, Acute Lymphocytic)
Larson Regimen (ALL)
Linker Protocol (ALL)
PVA (POG 8602)
Leukemia, acute myeloid:
5 + 2
7 + 3 (Daunorubicin)
7 + 3 (Idarubicin)
7 + 3 (Mitoxantrone)
7 + 3 + 7
EMA 86
FLAG (AML)
FLAG-IDA
Leukemia, acute promyelocytic: Tretinoin-Daunorubicin-Cytarabine (APL)
Leukemia, chronic lymphocytic: OFAR (CLL)
Leukemia, chronic myeloid: Interferon Alfa-2b-Cytarabine (CML)
Lymphoma, Hodgkin's disease: mini-BEAM
Lymphoma, non-Hodgkin's:
Cisplatin-Cytarabine-Dexamethasone (NHL Regimen)
CODOX-M
CODOX-M/IVAC
COMLA
ESHAP
Hyper-CVAD (Lymphoma, non-Hodgkin's)
Oxaliplatin-Cytarabine-Dexamethasone (NHL Regimen)
Pro-MACE-CytaBOM
Lymphoma, non-Hodgkin's (Burkitt's): CODOX-M/IVAC
Lymphoma, non-Hodgkin's (Mantle cell): Hyper-CVAD + Rituximab
Neuroblastoma: N4SE Protocol
Retinoblastoma: 8 in 1 (Retinoblastoma)
Administration: I.V.
Infuse as a continuous infusion or infuse over 1-3 hours (infusion rate based on protocol). GI adverse effects may be more pronounced with divided I.V. bolus doses than with continuous infusion.
Administration: Other
I.T.: Intrathecal doses should be administered as soon as possible after preparation.
May also be administered SubQ.
Administration: I.V. Detail
pH:5-7.4
BMT only: Risk of cerebellar toxicity increases with creatinine clearance <60 mL/minute, age older than 50 years, pre-existing CNS lesion, and alkaline phosphatase levels exceeding 3 times the upper limit of normal. Conjunctivitis is prevented and treated with saline or corticosteroid eye drops. As prophylaxis, eye drops should be started 6-12 hours before initiation of cytarabine and continued 24 hours following the last dose.
Monitoring Parameters
Liver function tests, CBC with differential and platelet count, serum creatinine, BUN, serum uric acid
Patient Education
This drug is administered by infusion or injection. Report immediately any redness, swelling, burning, or pain at injection/infusion site; sudden difficulty breathing or swallowing; chest pain; or chills. Maintain adequate hydration. You will be more susceptible to infection. May cause nausea, vomiting, loss of appetite, diarrhea, mouth sores, dizziness, headache, confusion, or brittle or dry hair or loss of hair (may reverse after treatment). Report immediately any signs of respiratory distress, chest pain or palpitations, CNS changes, change in gait, skin rash or ulceration, unusual bruising or bleeding, persistent GI upset, yellowing of eyes or skin, change in color of urine, pain on urination, blackened stool, pain passing stool, pain or numbness in joints or muscles, blurred vision, or change in visual acuity.
Additional Information
I.V. doses ≥1.5 g/m2 may produce conjunctivitis which can be ameliorated with prophylactic use of corticosteroid (0.1% dexamethasone) eye drops. Dexamethasone eye drops should be administered at 1-2 drops every 6 hours during and for 2-7 days after cytarabine is done.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Mucositis
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause sedation or confusion
Mental Health: Effects on Psychiatric Treatment
May cause myelosuppression; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Use caution in presence of impaired renal or hepatic function, prior bone marrow suppression, or prior CNS disease; dosage adjustment may be necessary. Ocular pain and conjunctivitis reactions may be reduced with ophthalmic corticosteroid premedication. Patient should be monitored closely throughout treatment, especially with high-dose regimens, for adverse gastrointestinal and pulmonary response, CNS toxicities, and cardiomyopathy.
Oncology: Emetic Potential
>1000 mg/m2: Moderate (30% to 90%)
100-200 mg/m2: Low (10% to 30%)
Oncology: Bone Marrow Comments
Risk of cerebellar toxicity increases with creatinine clearance <60 mL/minute, age older than 50 years, pre-existing CNS lesion, and alkaline phosphatase levels exceeding 3 times the upper limit of normal. Conjunctivitis is prevented and treated with saline or corticosteroid eye drops. As prophylaxis, eye drops should be started 6-12 hours before initiation of cytarabine and continued 24 hours following the last dose.
Oncology: Bone Marrow - High Dose
I.V.: 2-3 g/m2/dose every 12-24 hours for 4-12 doses; duration of infusion is 1-3 hours; maximum single-agent dose: 36 g/m2; generally combined with other high-dose chemotherapeutic drugs or total body irradiation (TBI).
Oncology: Bone Marrow - Unique Toxicity
Central nervous system: Cerebellar toxicity which includes nystagmus, dysarthria, disdiadochokinesis, slurred speech; cerebral toxicity which includes somnolence, confusion
Dermatologic: Rash, desquamation may occur
Gastrointestinal: Severe nausea and vomiting, mucositis, diarrhea, ageusia
Ocular: Photophobia, excessive tearing, blurred vision, local discomfort, chemical conjunctivitis, optic neuropathy, visual loss
Respiratory: Noncardiogenic pulmonary edema (onset 22-27 days following completion of therapy)
Miscellaneous: Anosmia
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution: 100 mg [contains benzyl alcohol (in diluent)], 500 mg [contains benzyl alcohol (in diluent)], 1 g [contains benzyl alcohol (in diluent)], 2 g [DSC] [contains benzyl alcohol (in diluent)]
Injection, solution: 20 mg/mL (25 mL) [contains benzyl alcohol]; 100 mg/mL (20 mL)
Injection, solution [preservative free]: 20 mg/mL (5 mL, 50 mL); 100 mg/mL (20 mL)
References
Adès L, Chevret S, Raffous, et al, “Is Cytarabine Useful in the Treatment of Acute Promyelocytic Leukemia? Results of a Randomized Trial From the European Acute Promyelocytic Leukemia Group,” J Clin Oncol, 2006, 24(36):5703-10.
Adès L, Sanz MA, Chevret S, et al, “Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (APL): A Comparison of French-Belgian-Swiss and PETHEMA Results,” Blood, 2008, 111(3):1078-84.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 98, 170.
Bleyer WA, Coccia PF, Sather HN, et al, “Reduction in Central Nervous System Leukemia With a Pharmacokinetically Derived Intrathecal Methotrexate Dosage Regimen,” J Clin Oncol, 1983, 1(5):317-25.
Capizzi RL, “Curative Chemotherapy for Acute Myeloid Leukemia: The Development of High-Dose Ara-C From the Laboratory to Bedside,” Invest New Drugs, 1996, 14(3):249-56.
Capizzi RL, White JC, Powell BL, et al, “Effect of Dose on the Pharmacokinetic and Pharmacodynamic Effects of Cytarabine,” Semin Hematol, 1991, 28(3 Suppl 4):54-69.
Cassileth PA, Harrington DP, Appelbaum FR, et al, “Chemotherapy Compared With Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission,” N Engl J Med, 1998, 339(23):1649-56.
Chiu A, Kohler S, McGuire J, et al, “Cytarabine-Induced Acute Generalized Exanthematous Pustulosis,” J Am Acad Dermatol, 2002, 47(4):633-5.
Cortes J, O'Brien SM, Pierce S, et al, “The Value of High-Dose Systemic Chemotherapy and Intrathecal Therapy for Central Nervous System Prophylaxis in Different Risk Groups of Adult Acute Lymphoblastic Leukemia,” Blood, 1995, 86(6):2091-7.
DeAngelis LM and Boutros D, “Leptomeningeal Metastasis,” Cancer Invest, 2005, 23(2):145-54.
de Lemos ML, Monfared S, Denyssevych T, et al, “Evaluation of Osmolality and pH of Various Concentrations of Methotrexate, Cytarabine, and Thiotepa Prepared in Normal Saline, Sterile Water for Injection, and Lactated Ringers's Solution for Intrathecal Administration,” J Oncol Pharm Pract, 2009, 15(1):45-52.
Floyd J, Mirza I, Sachs B, et al, "Hepatotoxicity of Chemotherapy," Semin Oncol, 2006, 33(1):50-67.
Floyd JD, Nguyen DT, Lobins RL, et al, “Cardiotoxicity of Cancer Therapy,” J Clin Oncol, 2005, 23(30):7685-96.
Gardin C, Turlure P, Fagot T, et al, “Postremission Treatment of Elderly Patients With Acute Myeloid Leukemia in First Complete Remission After Intensive Induction Chemotherapy: Results of the Multicenter Randomized Acute Leukemia French Association (ALFA) 9803 Trial,” Blood, 2007, 109(12):5129-35.
Gaynon PS, Steinherz PG, Bleyer WA, et al, “Improved Therapy for Children With Acute Lymphoblastic Leukemia and Unfavorable Presenting Features: A Follow-Up Report of the Childrens Cancer Group Study CCG-106,” J Clin Oncol, 1993, 11(11):2234-42.
Glantz MJ, LaFollette S, Jaeckle KA, et al, “Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis,” J Clin Oncol, 1999, 17(10):3110-6.
Hiddemann W, “Cytosine Arabinoside in the Treatment of Acute Myeloid Leukemia: The Role and Place of High-Dose Regimens,” Ann Hematol, 1991, 62(4):119-28.
Jacobson JO, Polovich M, McNiff KK, et al, "American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards," J Clin Oncol, 2009, 27(32):5469-75.
Kerr JZ, Berg S, and Blaney SM, “Intrathecal Chemotherapy,” Crit Rev Oncol Hematol, 2001, 37(3):227-36.
Kintzel PE and Dorr RT, “Anticancer Drug Renal Toxicity and Elimination: Dosing Guidelines for Altered Renal Function,” Cancer Treat Rev, 1995, 21(1):33-64.
Koren G, Beatty K, Seto A, et al, “The Effects of Impaired Liver Function on the Elimination of Antineoplastic Agents,” Ann Pharmacother, 1992, 26(3):363-71.
Lin WY, Liu HC, Yeh TC, et al, “Triple Intrathecal Therapy Without Cranial Irradiation for Central Nervous System Preventive Therapy in Childhood Acute Lymphoblastic Leukemia,” Pediatr Blood Cancer, 2008, 50(3):523-7.
Matloub Y, Lindemulder S, Gaynon PS, et al, “Intrathecal Triple Therapy Decreases Central Nervous System Relapse but Fails to Improve Event-Free Survival When Compared With Intrathecal Methotrexate: Results of the Children's Cancer Group (CCG) 1952 Study for Standard-Risk Acute Lymphoblastic Leukemia, Reported by the Children's Oncology Group,” Blood, 2006, 108(4):1165-73.
Morgan C, Tillett T, Braybrooke J, et al, “Management of Uncommon Chemotherapy-Induced Emergencies,” Lancet Oncol, 2011 [epub ahead of print].
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Acute Myeloid Leukemia,” Version 3.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/aml.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Central Nervous System Cancers,” Version 1.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf
National Comprehensive Cancer Network® (NCCN) “Practice Guidelines in Oncology: Chronic Myelogenous Leukemia Version 2.2010.” Available at http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Hodgkin Disease/Lymphoma,” Version 1.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/hodgkins.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Non-Hodgkin's Lymphomas,” Version 1.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf
Pease CL, Horton TM, McClain KL, et al, “Aseptic Meningitis in a Child After Systemic Treatment With High Dose Cytarabine,” Pediatr Infect Dis J, 2001, 20(1):87-9.
Pegram AA and Kennedy LD, “Prevention and Treatment of Veno-Occlusive Disease,” Ann Pharmacother, 2001, 35(7-8):935-42.
Pieters R, Schrappe M, De Lorenzo P, et al, “A Treatment Protocol for Infants Younger Than 1 Year With Acute Lymphoblastic Leukaemia (Interfant-99): An Observational Study and a Multicentre Randomised Trial,” Lancet, 2007, 370(9583):240-50.
Smith G, Damon LE, Rugo HS, et al. “High-Dose Cytarabine Dose Modification Reduces the Incidence of Neurotoxicity in Patients With Renal Insufficiency,” J Clin Oncol, 1997, 15(2): 833-9.
Stasi R, Venditti A, Del Poeta G, et al, “High-Dose Chemotherapy in Adult Acute Myeloid Leukemia: Rationale and Results,” Leuk Res, 1996, 20(7):535-49.
Storring JM, Minden MD, Kao S, et al, “Treatment of Adults With BCR-ABL Negative Acute Lymphoblastic Leukaemia With a Modified Paediatric Regimen,” Br J Haematol, 2009, 146(1):76-85.
Trissel LA, King KM, Zhang Y, et al, “Physical and Chemical Stability of Methotrexate, Cytarabine, and Hydrocortisone in Elliott's B Solution for Intrathecal Use,” J Oncol Pharm Pract, 2002, 8(1):27-32.
Truica CI and Frankel SR, “Acute Rhabdomyolysis as a Complication of Cytarabine Chemotherapy for Acute Myeloid Leukemia: Case Report and Review of Literature,” Am J Hematol, 2002, 70(4):320-3.
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Last full review/revision May 2011
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