cytarabine

Pyrimidine Analogs

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
Pediatrics:
IV Doses 3 g/m2/day or higher: High
IV Doses 75 mg/m2/dose: Moderate
Adults:
IV Doses: Higher than 1000 mg/m2: Moderate
IV Doses: 1,000 mg/m2 or lower: Low
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Nonvesicant

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

Reconstitution of powder for injection for intravenous use:
Do not use solutions containing benzyl alcohol in neonates.
NOTE: Do NOT use Bacteriostatic diluents to prepare cytarabine for intrathecal use.
The dry powder may be diluted in minimal volumes for a final concentration of 100 mg/mL. More concentrated solutions may be necessary for subcutaneous or intrathecal administration.
100-mg vial: add 5 mL of bacteriostatic water for injection with benzyl alcohol 0.945% w/v as a preservative to give a solution containing 20 mg/mL of cytarabine.
500-mg or 1-gram vial: add 10 mL of bacteriostatic water for injection with benzyl alcohol 0.945% w/v as a preservative to give a solution containing 50 or 100 mg/mL, respectively, of cytarabine.
2-gram vial: add 20 mL of bacteriostatic water for injection with benzyl alcohol 0.945% w/v as a preservative to give a solution containing 100 mg/mL of cytarabine.
NOTE: For high dose cytarabine regimens, preservative-free diluents may be considered for reconstitution to avoid high concentrations of benzyl alcohol.
Reconstituted solutions containing benzyl alcohol are stable for 48 hours. Cloudy solutions should be discarded. Solutions reconstituted with preservative-free diluents should be used immediately.
Direct IV injection:
Withdraw the appropriate amount from the commercially available 20 mg/mL injection or a reconstituted vial.
Administer each 100 mg of cytarabine by direct IV push over 1 to 3 minutes.
Intermittent IV infusion:
Further dilute the appropriate dose of the injection solution in 5% Dextrose injection or 0.9% Sodium Chloride injection.
Infuse IV over 30 minutes to 6 hours. High-dose cytarabine (off-label use) infusions are typically administered over 3 hours.
Continuous IV infusion:
Further dilute the appropriate dose of the injection solution in 5% Dextrose injection or 0.9% Sodium Chloride injection.

Do not use the pharmacy bulk package for intrathecal administration.
NOTE: Do NOT use diluent supplied by the manufacturer to prepare intrathecal cytarabine as it contains benzyl alcohol.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
 
Reconstitution of powder for injection for intrathecal use:
NOTE: Do NOT use Bacteriostatic diluents to prepare cytarabine for intrathecal use as they contain benzyl alcohol.
Reconstitute the powder for injection to a final concentration of 100 mg/mL with autologous spinal fluid or preservative-free 0.9% Sodium Chloride injection.
Reconstituted solution may be further diluted up to a total volume of 5 mL.
Use solutions immediately.

anaphylactoid reactions / Rapid / 0-1.0
respiratory arrest / Rapid / 0-1.0
cardiac arrest / Early / 0-1.0
pancytopenia / Delayed / Incidence not known
bowel necrosis / Delayed / Incidence not known
esophageal ulceration / Delayed / Incidence not known
pneumatosis cystoides intestinalis / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
coma / Early / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
seizures / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
tumor lysis syndrome (TLS) / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
cardiomyopathy / Delayed / Incidence not known
leukoencephalopathy / Delayed / Incidence not known

leukopenia / Delayed / 10.0
thrombocytopenia / Delayed / 10.0
anemia / Delayed / 10.0
oral ulceration / Delayed / 10.0
edema / Delayed / Incidence not known
bleeding / Early / Incidence not known
bone marrow suppression / Delayed / Incidence not known
colitis / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
conjunctivitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
pneumonitis / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
neuritis / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
confusion / Early / Incidence not known
encephalopathy / Delayed / Incidence not known
psychosis / Early / Incidence not known
ataxia / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
impaired cognition / Early / Incidence not known
hyperuricemia / Delayed / Incidence not known
urinary retention / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
bone pain / Delayed / Incidence not known

diarrhea / Early / 10.0
anorexia / Delayed / 10.0
nausea / Early / 10.0
vomiting / Early / 10.0
rash / Early / 10.0
fever / Early / 10.0
urticaria / Rapid / Incidence not known
infection / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
dizziness / Early / Incidence not known
tremor / Early / Incidence not known
diplopia / Early / Incidence not known
headache / Early / Incidence not known
drowsiness / Early / Incidence not known
maculopapular rash / Early / Incidence not known
myalgia / Early / Incidence not known

Cytarabine therapy requires an experienced clinician and should be used only by clinicians experienced in myelosuppressive cancer chemotherapy. Administration of cytarabine requires a specialized care setting. Patients receiving cytarabine, especially for induction, should be under close medical supervision in facilities with laboratory and supportive resources sufficient to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity. Treatment with cytarabine may result in severe and prolonged bone marrow suppression, which is the main toxic effect. Anemia, leukopenia, and thrombocytopenia may occur. Other toxicity includes chemotherapy-induced nausea/vomiting, diarrhea, abdominal pain, oral ulceration, and hepatotoxicity. Frequent monitoring of complete blood counts (CBC), electrolytes, liver function, and bone marrow are necessary. Patients with an active infection should be treated prior to receiving cytarabine, when possible. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy. Consider the possible benefit and the known toxic effects of cytarabine and be familiar with the cytarabine prescribing information before deciding to treat a patient with cytarabine.

Rx

Pyrimidine antimetabolite anitneoplastic agent; used in the treatment of hematologic malignancies; has limited cytotoxicity in solid tumors; a liposomal product is also available (see Cytarabine Liposomal monograph).

100 mg/m2 daily for 7 days via continuous IV infusion or cytarabine 100 mg/m2 IV every 12 hours for 7 days; give in combination with other anticancer drugs.[61919]

100 mg/m2 IV daily as a continuous IV infusion on days 1 to 7 in combination with idarubicin 8 mg/m2 IV daily on days 1, 2, 3, 4, and 5 and lomustine 200 mg/m2 orally on day 1 was evaluated as induction therapy in a randomized, phase 3 trial (the LAM-SA 2007 FILO Trial). Patients who achieved a complete remission (CR) or CR with incomplete recovery after 1 induction course received 1 cycle of consolidation therapy and 6 reinduction courses with subcutaneous cytarabine plus idarubicin and lomustine.[63748]

50 mg/m2 subcutaneously every 12 hours on days 1, 2, 3, 4, and 5 in combination with idarubicin 8 mg/m2 IV daily on days 1, 2, and 3, and lomustine 80 mg orally on day 1 was evaluated as consolidation therapy in patients who achieved a complete remission (CR) or CR with incomplete recovery after 1 induction cycle of cytarabine, idarubicin, and lomustine in a randomized, phase 3 trial (the LAM-SA 2007 FILO Trial). Following 1 cycle of consolidation therapy, patients received 6 reinduction courses of cytarabine 50 mg/m2 subcutaneously every 12 hours on days 1, 2, 3, 4, and 5; idarubicin 8 mg/m2 IV on day 1; and lomustine 40 mg orally on day 1. In this study, patients also received 6 months of maintenance therapy with alternating courses of 6-mercaptopurine and methotrexate.

20 mg subcutaneously twice daily on days 1 to 10 in combination with glasdegib 100 mg orally once daily. Repeat treatment cycles every 28 days until disease progression. Continue therapy for a minimum of 6 cycles in patients who do not have unacceptable toxicity. Therapy interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. At a median follow-up time of about 20 months, the overall survival time was significantly improved in patients who received glasdegib plus low-dose cytarabine (n = 77) compared with low-dose cytarabine alone (n = 38) (8.3 months vs. 4.3 months; hazard ratio = 0.46; 95% CI, 0.3 to 0.71; p = 0.0002) in a multicenter, open-label, randomized trial (the BRIGHT AML 1003 trial). Patients in this study were 55 years of age or older with newly-diagnosed AML and had at least 1 of the following criteria: age greater than 75 years; severe cardiac disease; a baseline Eastern Cooperative Oncology Group performance status of 2; or a baseline serum creatinine level greater than 1.3 mg/dL.[63777]

20 mg/m2 subcutaneously once daily on days 1 to 10 repeated every 28 days starting on day 1 of cycle 1 in combination with oral venetoclax. The venetoclax dose is increased during a ramp-up phase as follows: 100 mg on day 1; 200 mg on day 2; 400 mg on day 3; and 600 mg once daily on day 4 and beyond. Continue treatment until disease progression. At a median follow-up time of 12 months, the median overall survival (OS) time was nonsignificantly longer in patients with previously untreated acute myelogenous leukemia who received venetoclax plus low-dose cytarabine compared with placebo plus low-dose cytarabine (7.2 months vs. 4.1 months; hazard ratio (HR) = 0.75; 95% CI, 0.52 to 1.07; p = 0.11) in a multinational, randomized (2:1), double-blind, phase 3 trial (n = 211; the VIALE-C trial). However, the median OS time was significantly improved with venetoclax plus low-dose cytarabine following an additional 6 months of follow-up (8.4 months vs. 4.1 months; hazard ratio (HR) = 0.7; 95% CI, 0.5 to 0.99; p = 0.04). The complete remission (CR) (27% vs. 7%; p less than 0.001) and CR plus CR with partial hematologic recovery (CRh) by cycle 2 (48% vs. 13%; p less than 0.001) rates were significantly higher in the venetoclax plus low-dose cytarabine arm compared with the placebo plus low-dose cytarabine arm. Eligible patients (median age, 76 years; range, 36 to 93 years) in this trial were aged 75 years or older (approximately 58%) and/or had coexisting conditions that prevented the use of intensive chemotherapy (i.e., standard induction therapy). The CR and CRh rates were each 21% in a subgroup of 61 patients with newly diagnosed AML who were 75 years of age or older or had comorbidities who received venetoclax plus low-dose cytarabine in a nonrandomized trial.

As intensification or for treatment of refractory/relapsed ALL, 1 to 3 g/m2 IV every 12 hours for 8 to 12 doses.

20 mg/m2/day subcutaneously for 10 days each month plus interferon alfa-2b 5 million units/m2/day subcutaneously as continuous therapy (median duration of therapy, 34 months) was evaluated in a large randomized trial. Cytarabine therapy was initiated 2 weeks after interferon therapy had begun. All patients also received hydroxyurea 50 mg/kg/day (or less depending on WBC count) until a complete hematologic remission was achieved.

Various doses have been used including 200 mg/m2/day IV as a continuous infusion for 9 days; 500 mg/m2 IV every 12 hours for 3 days; or 3 g/m2/day IV for 5 days.

Doses of 5 to 70 mg/m2 intrathecally prepared in 5 to 10 mL of preservative-free diluent such as 0.9% sodium chloride or Ringer's lactate have been used. Do not use the diluent provided by the manufacturer because it contains benzyl alcohol. Alternatively, the following doses may be used in children: children older than 3 years, 70 mg; children 2 to 3 years, 50 mg; children 1 to 2 years, 30 mg; children younger than 1 year, 20 mg.

100 mg/m2 IV every 12 hours for 4 days as part of dexa-BEAM and mini-BEAM has been studied with favorable response rates; additionally, 1 to 2 doses of 2,000 mg/m2 IV as part of DHAP and ESHAP has been studied in nonrandomized trials. In a randomized clinical trial of 144 patients, 81% of patients achieved a response (complete response [CR], 27%; partial response [PR], 54%) following 2 initial cycles of dexamethasone plus cytarabine 100 mg/m2 IV every 12 hours on days 4 to 7, carmustine, etoposide, and melphalan (dexa-BEAM) (with colony-stimulating factor starting on day 8 until leukocyte recovery); patients were then randomized to receive either 2 additional cycles of dexa-BEAM or high-dose chemotherapy with BEAM followed by autologous stem-cell transplant (ASCT). Patients who received BEAM/ASCT had a significantly improved 3-year freedom from treatment failure rate (55% vs. 34%; p = 0.019) but not 3-year overall survival (OS) rate (71% vs. 65%) compared with patients who received 2 additional courses of dexa-BEAM. In nonrandomized studies, favorable overall response rates have been seen when cytarabine has been studied as part of the DHAP (cytarabine 2,000 mg/m2 IV over 3 hours every 12 hour on day 2, dexamethasone, and cisplatin with filgrastim 24 hours after the last cytarabine dose until leukocyte recovery, and corticosteroid eye drops every 12 hours starting 12 hours before and continuing for 2 days after the last cytarabine dose), ESHAP (cytarabine 2000 mg/m2 on day 5, etoposide, methylprednisolone, and cisplatin with filgrastim on days 6 to 18), and mini-BEAM (cytarabine 100 mg/m2 every 12 hours on days 2 to 5, carmustine, etoposide, and melphalan) regimens.

2 grams/m2 IV over 3 hours every 12 hours for 2 doses on day 2 in combination with cisplatin 100 mg/m2 as a continuous IV infusion over 24 hours on day 1 and dexamethasone 40 mg IV/PO once daily on days 1, 2, 3, and 4. Treatment cycles were repeated every 3 to 4 weeks.

1 gram/m2 IV over 3 hours every 12 hours for 2 doses on day 2 in combination with cisplatin 100 mg/m2 as a continuous IV infusion over 24 hours on day 1 and dexamethasone 40 mg IV/PO once daily on days 1, 2, 3, and 4. Treatment cycles were repeated every 3 to 4 weeks.

2 grams/m2 IV every 12 hours on day 2 as part of R-DHAP or 2 grams/m2 IV on day 5 as part of R-ESHAP has been studied. In a multicenter, randomized, phase III trial in 396 patients, the overall response rates (ORR) (62.8% vs. 63.5%) and mobilization-adjusted ORR (primary endpoint) (54.5% vs. 52.5%) were not significantly different following salvage therapy with rituximab plus cytarabine dexamethasone, and cisplatin (R-DHAP) or rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE) repeated every 3 weeks for 3 cycles; additionally, there were no significant differences in 3-year event-free survival (EFS) (35% vs. 26%), progression-free survival (PFS) (42% vs. 31%), and overall survival (OS) (51% vs. 47%) between the R-DHAP and R-ICE arms. In this study, patients with prior rituximab exposure had significantly worse EFS, PFS, and OS. In a retrospective cohort analysis of 163 patients with relapsed or refractory diffuse large B-cell NHL, rituximab plus cytarabine, etoposide, methylprednisolone, and cisplatin (R-ESHAP) repeated every 3 to 4 weeks led to an ORR of 73% (CR, 45%) and 5-year PFS and OS rates of 38% and 50%, respectively. In a multivariate analysis, prior rituximab exposure was associated with significantly worse PFS (relative risk (RR) = 2; 95% CI, 1.2 to 3.34) and OS (RR = 2.23; 95% CI, 1.29 to 3.86). DHAP and ESHAP regimens without rituximab have also produced favorable ORR rates in patients with relapsed or refractory NHL (all grades) in nonrandomized studies.

2 grams/m2 IV over 3 hours every 12 hours for 2 doses on day 2 as part of the DHAP regimen with dexamethasone 40 mg PO/IV on days 1, 2, 3, and 4 and cisplatin 100 mg/m2 as a continuous IV infusion over 24 hours on day 1 in combination with ofatumumab 1,000 mg IV on days 1 and 8 of cycle 1 then ofatumumab 1,000 mg IV on day 1 of cycles 2 and 3 was evaluated in a randomized, phase III trial (n = 445; the ORCHARRD trial). Cycles were repeated every 21 days for a total of 3 cycles of therapy. Granulocyte colony-stimulating factor use was recommended as follows: filgrastim 5 mcg/kg on days 6 to 13 or pegfilgrastim 6 mg on day 6 on cycles of therapy with no stem-cell mobilization and filgrastim 5 to 10 mcg/kg on days 6 to 13 on cycles of therapy that were followed by stem-cell mobilization. Central nervous system prophylaxis using intrathecal therapy was permitted. Supportive care during treatment consisted of irradiated blood products, oral antibiotics, and antifungal prophylaxis as clinically indicated.

†Indicates off-label use

Dosage should be modified depending on clinical response and degree of hepatic impairment, but no quantitative recommendations are available.

CrCl 60 mL/minute or greater: No dosage adjustment needed.
CrCl less than 60 mL/minute: Increased risk of cerebellar and cerebral toxicity with high dose regimens. Recommended dosage adjustments are as follows: For a serum creatinine of 1.5 to 1.9 mg/dL or increase of serum creatinine from baseline of 0.5 to 1.2 mg/dL during treatment, reduce the dose of cytarabine from 2 to 3 g/m2 per day to 1 g/m2 per day. For a serum creatinine 2 mg/dL or greater or if the change in baseline serum creatinine was greater than 1.2 mg/dL, reduce the dose of cytarabine from 2 to 3 g/m2 per day to 100 mg/m2 per day.
CrCl 40 to 60 mL/minute: For doses more than 2 g/m2 per dose, decrease the dose to 1 g/m2 per dose. For doses 750 mg to 1 g/m2 per dose, decrease to 500 mg/m2 per dose.
CrCl less than 40 mL/minute: For doses more than 750 mg/m2 per dose, give a dose less than or equal to 200 mg/m2 per day.

Acetaminophen; Ibuprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Amlodipine; Celecoxib: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Anticoagulants: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Antithrombin III: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Apixaban: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Argatroban: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Asparaginase Erwinia chrysanthemi: (Major) Acute pancreatitis has been reported in patients being treated with cytarabine who have had prior treatment with L-asparaginase. This may be schedule dependent. In addition, L-asparaginase may have schedule-dependent synergy and antagonism with high-dose cytarabine.
Betrixaban: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Bivalirudin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Bupivacaine; Meloxicam: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Celecoxib: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Celecoxib; Tramadol: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
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.
Clofarabine: (Minor) Clofarabine-cytarabine combination trials have not been completed to date; however, clofarabine is mechanistically like fludarabine. Thus, theoretically, a sequence-related interaction may occur during concurrent clofarabine and cytarabine treatment. The anti-cancer activity of cytarabine may be increased if clofarabine is given prior; while the activity of clofarabine may be decreased if cytarabine is given prior.
Cyclophosphamide: (Moderate) Monitor for signs and symptoms of cardiac dysfunction if coadministration of cyclophosphamide with cytarabine is necessary as there is an increased risk of cardiotoxicity.
Dabigatran: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Dalteparin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Decitabine; Cedazuridine: (Major) Avoid the concomitant use of decitabine; cedazuridine with drugs that are metabolized by the enzyme cytidine deaminase (CDA), such as cytarabine; the cytotoxicity of cytarabine may be increased. Cedazuridine is a CDA inhibitor. CDA is one of the enzymes responsible for the metabolism of cytarabine to form inactive metabolites.
Desirudin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Diclofenac: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Diclofenac; Misoprostol: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Diflunisal: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Diphenhydramine; Ibuprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Diphenhydramine; Naproxen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Edoxaban: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Enoxaparin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Etodolac: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Fenoprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Flucytosine: (Major) Cytarabine, ARA-C can competitively inhibit flucytosine, antagonizing its antifungal activity.
Fludarabine: (Minor) Prior or concurrent administration of cytarabine, ARA-C with fludarabine results in inhibition of the metabolism of fludarabine to its active triphosphate. Fludarabine administration should generally precede cytarabine, ARA-C administration.
Flurbiprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Fondaparinux: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Gentamicin: (Minor) Cytarabine may reduce the efficacy of gentamicin in certain infections. The lack of a prompt therapeutic response may indicate the need for reevaluation of antibacterial therapy.
Heparin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Hydrocodone; Ibuprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Hydroxyurea: (Minor) Hydroxyurea potentiates the activity of cytarabine, ARA-C by depleting the cell of another nucleoside, deoxycytidine triphosphate, which would otherwise compete with cytarabine for activity in the cell. Some clinicians have recommended decreasing the dose of cytarabine when it is given concurrently with hydroxyurea.
Ibuprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Ibuprofen; Famotidine: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Ibuprofen; Oxycodone: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Ibuprofen; Pseudoephedrine: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Indomethacin: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Ketoprofen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Ketorolac: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
L-Asparaginase Escherichia coli: (Major) Acute pancreatitis has been reported in patients being treated with cytarabine who have had prior treatment with L-asparaginase. This may be schedule dependent. In addition, L-asparaginase may have schedule-dependent synergy and antagonism with high-dose cytarabine.
Live Vaccines: (Contraindicated) Do not administer live vaccines to cytarabine recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving cytarabine. At least 2 weeks before initiation of cytarabine therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Cytarabine recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Meclofenamate Sodium: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Mefenamic Acid: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Meloxicam: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Methotrexate: (Minor) Pre-treatment with methotrexate enhances Ara-CTP formation resulting in increased cytarabine induced cytotoxicity. Simultaneous administration of cytarabine and methotrexate is associated with increased retention of Ara-CTP within the cell.
Mitoxantrone: (Minor) There is a synergistic cytotoxic effect seen during the concomittant administration of mixotrantrone and high-dose cytarabine, ARA-C. In studies of leukemic blast cells from patients treated with this combination, there was enhanced accumulation of araCTP, the active form of cytarabine, in these cells.
Nabumetone: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Naproxen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Naproxen; Esomeprazole: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Naproxen; Pseudoephedrine: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Nonsteroidal antiinflammatory drugs: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Oxaprozin: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Pegaspargase: (Major) Acute pancreatitis has been reported in patients being treated with cytarabine who have had prior treatment with L-asparaginase. This may be schedule dependent. L-asparaginase may have schedule-dependent synergy and antagonism with high-dose cytarabine. Similar reactions may occur with pegaspargase.
Pentosan: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Piroxicam: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Rivaroxaban: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
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.
Sulindac: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Sumatriptan; Naproxen: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Tolmetin: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
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.
Valdecoxib: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity.
Warfarin: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.

Cytarabine Intrathecal Inj Sol: 1mL, 20mg, 100mg
Cytarabine Intravenous Inj Sol: 1mL, 20mg, 100mg
Cytarabine Subcutaneous Inj Sol: 1mL, 20mg, 100mg

6 g/m2/day IV; 100 mg/m2/day SC; 70 mg/m2 intrathecally.

6 g/m2/day IV; 100 mg/m2/day SC; 70 mg/m2 intrathecally.

6 g/m2/day IV; 100 mg/m2/day SC; 70 mg/m2 intrathecally.

6 g/m2/day IV; 100 mg/m2/day SC; 70 mg/m2 intrathecally.

Cytarabine is an S-phase specific cytotoxic agent and has no effect on non-dividing cells or cells in any other phase. The cytotoxicity of cytarabine is also dependent upon the rate of DNA synthesis and the duration of exposure of cells to cytarabine. Therefore, in tissue cultures, cytotoxicity is greatest if cells are exposed to cytarabine for extended periods during maximal DNA synthesis to allow cytarabine to be incorporated into a larger number of cells as they pass through the S-phase. Intracellularly, cytarabine is metabolized by deoxycytidine kinases to form 1-beta-D-arabinofuranosylcytosine-5'-triphosphate (Ara-CTP). Ara-CTP competitively inhibits DNA polymerase-alpha and halts DNA strand elongation and repair, which seems to decrease the phosphorylation of cytarabine to the active metabolite. The most important cytotoxic effect of Ara-CTP is incorporation into DNA. Once incorporated into DNA, the tumor cells are unable to remove Ara-CTP and this results in inhibition of template function and chain elongation. In addition, deoxycytidine levels are reduced within the cell due to the production of Ara-CTP. Both of these processes block further polymerization of DNA and lead to shortened DNA strands. Cytarabine also causes unusual multiple duplications of DNA strands that increase the possibility of recombination, crossover, and gene amplification.
 
Other actions of cytarabine include inhibition of ribonucleotide reductase, formation of Ara-CDP-choline and induction of cellular differentiation. Ara-CDP-choline is an analog of cytidine 5'-diphosphocholine (CDP-choline) and inhibits synthesis of membrane glycoproteins and glycolipids altering membrane structure, stability, antigenicity and function. Cytarabine can promote differentiation of leukemic cells and decrease c-myc expression.

Cytarabine is administered intravenously, subcutaneously or intrathecally. Cytarabine is not given orally due to extensive deamination within gut lumen resulting in only 20% absorption. Cytarabine distributes rapidly throughout the body tissues and is transported into cells by active transport. It crosses the blood-brain barrier resulting in cerebrospinal concentrations 20—50% of plasma concentrations. With high doses, cytarabine achieves significant concentrations in tears. The drug undergoes metabolism to its active form via cytidine kinase then both the parent drug and active metabolite undergo deamination by cytidine deaminase to an inactive metabolite, uracil arabinoside (Ara-U). Cytidine deaminase is located primarily in the liver, kidneys, GI mucosa, and granulocytes. The degradation pathway can be saturated at higher doses yielding a higher amount of active metabolites. Ara-U has a half-life of 3—6 hours and enhances the activation of cytarabine through negative feedback inhibition of cytidine deaminase in leukemic cells. Ara-U further potentiates the effects of cytarabine by causing cytostasis in the S-phase with enhanced anabolism and cytotoxicity of subsequent cytarabine doses. Excretion of cytarabine is biphasic. The majority of cytarabine is excreted via the urine in the form of Ara-U. Ninety percent of the cytarabine dose is eliminated in the urine in 24 hours.
 
Once cytarabine enters the CSF, the tissues that have the greatest contact with the CSF phosphorylate the drug. The half-life of conventional cytarabine in the CSF is longer (2—11 hours) than in plasma. The CSF clearance of cytarabine approximates the bulk flow rate suggesting that elimination occurs through this route. During high-dose cytarabine therapy and renal insufficiency, Ara-U accumulates in CSF and inhibits cytidine deaminase resulting in higher concentrations of Ara-CTP, which is neurotoxic.

Subcutaneous or IM administration results in lower peak plasma levels than IV administration. Following intravenous administration, the initial phase half-life of 8—20 minutes and is due to extensive degradation in the liver. The terminal phase half-life is 1—3 hours but cytarabine serum concentrations during this phase are only significant with high-dose regimens.

Subcutaneous or IM administration results in lower peak plasma levels than IV administration.

Subcutaneous or IM administration results in lower peak plasma levels than IV administration.

Cytarabine, ARA-C is a FDA pregnancy risk category D drug. Cytarabine is a known teratogen and should not be used during the first trimester of pregnancy. Deformities of the head and limbs are most common. Use in the second and third trimesters is safer but constitutes a considerable risk. Females of childbearing potential should be cautioned to avoid getting pregnant. If pregnancy occurs during cytarabine treatment, women should be counseled regarding risks and options for the pregnancy. Reports of pancytopenia, leukopenia, anemia, thrombocytopenia, sepsis and death have occurred during the neonatal period to infants exposed to cytarabine in utero. Infants whose mothers have received cytarabine during pregnancy should be closely observed.

It is uncertain whether cytarabine is distributed into breast milk. According to the manufacturer, because of the potential for serious adverse effects in the infant, a decision should be made to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.