Only health care providers experienced in cancer chemotherapy should use cytarabine.
For induction therapy, patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The main toxic effect of cytarabine is bone marrow suppression with leukopenia, thrombocytopenia, and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and hepatic dysfunction.
The health care provider must judge possible benefit to the patient against known toxic effects of this drug in considering the advisability of therapy with cytarabine. Before making this judgment or beginning treatment, the health care provider should be familiar with the following text.
Note: Antiemetics may be recommended to prevent nausea and vomiting; IV doses >1,000 mg/m2 are associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Consider hydration and antihyperuricemic therapy to prevent tumor lysis syndrome.
Acute lymphoblastic leukemia (off-label dosing):
Induction regimen, relapsed or refractory: IV: 3,000 mg/m2 over 3 hours daily for 5 days (in combination with idarubicin [day 3]) (Weiss 2002).
Dose-intensive regimen: IV: 3,000 mg/m2 over 2 hours every 12 hours days 2 and 3 (4 doses/cycle) of even numbered cycles (in combination with methotrexate; alternates with Hyper-CVAD) (Kantarjian 2000).
CALGB 8811 regimen (Larson 1995):
Early-intensification phase: SUBQ: 75 mg/m2/dose days 1 to 4 and 8 to 11 (4-week cycle; repeat once).
Late-intensification phase: SUBQ: 75 mg/m2/dose days 29 to 32 and 36 to 39.
Linker protocol: Adults <50 years of age: IV: 300 mg/m2/day days 1, 4, 8, and 11 of even numbered consolidation cycles (in combination with teniposide) (Linker 1991).
CALGB 10403 regimen (Stock 2019; as part of multi-agent, multicourse chemotherapy; refer to protocol for further details):
Adults <40 years of age:
Remission consolidation phase (course 2): IV, SUBQ: 75 mg/m2 on days 1 to 4, 8 to 11, 29 to 32, and 36 to 39.
Delayed intensification phase (course 4): IV, SUBQ: 75 mg/m2 on days 29 to 32 and 36 to 39.
Acute myeloid leukemia remission induction: Standard-dose (manufacturer's labeling; in combination with other chemotherapy agents): IV: 100 mg/m2/day continuous infusion for 7 days or 200 mg/m2/day continuous infusion (as 100 mg/m2 over 12 hours every 12 hours) for 7 days.
7 + 3 regimens (a second induction course may be administered if needed; refer to specific references): IV: 100 mg/m2/day continuous infusion for 7 days (in combination with daunorubicin or idarubicin or mitoxantrone) (Arlin 1990; Dillman 1991; Fernandez 2009; Vogler 1992; Wiernik 1992) or (Adults <60 years) 200 mg/m2/day continuous infusion for 7 days (in combination with daunorubicin) (Dillman 1991).
Low-intensity therapy (off-label dosing):
Adults ≥65 years of age: SUBQ: 20 mg/m2/day for 14 days out of every 28-day cycle for at least 4 cycles (Fenaux 2010) or 10 mg/m2 every 12 hours for 21 days; if complete response not achieved, may repeat a second course after 15 days (Tilly 1990).
Adults ≥60 years of age (and ineligible for intensive chemotherapy): SUBQ: 20 mg/m2 once daily on days 1 to 10 every 28 days (in combination with venetoclax) until disease progression or unacceptable toxicity (Wei 2020).
Adults ≥55 years of age (and unsuitable for intensive therapy): SUBQ: 20 mg (flat dose) twice daily on days 1 to 10 every 28 days (in combination with glasdegib) until disease progression or unacceptable toxicity (Cortes 2019).
Acute myeloid leukemia consolidation (off-label use):
5 + 2 regimens: IV: 100 mg/m2/day continuous infusion for 5 days (in combination with daunorubicin or idarubicin or mitoxantrone) (Arlin 1990; Wiernik 1992).
5 + 2 + 5 regimen: IV: 100 mg/m2/day continuous infusion for 5 days (in combination with daunorubicin and etoposide) (Bishop 1996).
Single-agent: Adults ≤60 years of age: IV: 3,000 mg/m2 over 3 hours every 12 hours on days 1, 3, and 5 (total of 6 doses); repeat every 28 to 35 days for 4 courses (Mayer 1994).
Acute myeloid leukemia salvage treatment (off-label use):
CLAG regimen: IV: 2,000 mg/m2/day over 4 hours for 5 days (in combination with cladribine and G-CSF); may repeat once if needed (Wrzesień-Kuś 2003).
CLAG-M regimen: IV: 2,000 mg/m2/day over 4 hours for 5 days (in combination with cladribine, G-CSF, and mitoxantrone); may repeat once if needed (Wierzbowska 2008).
FLAG regimen: IV: 2,000 mg/m2/day over 4 hours for 5 days (in combination with fludarabine and G-CSF); may repeat once if needed (Montillo 1998).
GCLAC regimen: Adults 18 to 70 years (Becker 2011):
Induction: IV: 2,000 mg/m2 over 2 hours once daily for 5 days (in combination with clofarabine and filgrastim; administer 4 hours after initiation of clofarabine); may repeat induction once if needed.
Consolidation: IV: 1,000 mg/m2 over 2 hours once daily for 5 days (in combination with clofarabine and filgrastim; administer 4 hours after initiation of clofarabine) for 1 or 2 cycles.
HiDAC (high-dose cytarabine) ± an anthracycline: IV: 3,000 mg/m2 over 1 hour every 12 hours for 6 days (total of 12 doses) (Herzig 1985).
MEC regimen: IV: 1,000 mg/m2/day over 6 hours for 6 days (in combination with mitoxantrone and etoposide) (Amadori 1991) or
Adults <60 years of age: IV: 500 mg/m2/day continuous infusion days 1, 2, and 3 and days 8, 9, and 10 (in combination with mitoxantrone and etoposide); may administer a second course if needed (Archimbaud 1991; Archimbaud 1995).
Acute promyelocytic leukemia induction (off-label dosing): IV: 200 mg/m2/day continuous infusion for 7 days beginning on day 3 of treatment (in combination with tretinoin and daunorubicin) (Ades 2006; Ades 2008; Powell 2010).
Acute promyelocytic leukemia consolidation (off-label use):
In combination with idarubicin and tretinoin: High-risk patients (WBC ≥10,000/mm3) (Sanz 2010): Adults ≤60 years of age:
First consolidation course: IV: 1,000 mg/m2/day for 4 days.
Third consolidation course: IV: 150 mg/m2 every 8 hours for 4 days.
In combination with idarubicin, tretinoin, and thioguanine: High-risk patients (WBC >10,000/mm3) (Lo Coco 2010): Adults ≤61 years of age:
First consolidation course: IV: 1,000 mg/m2/day for 4 days.
Third consolidation course: IV: 150 mg/m2 every 8 hours for 5 days.
In combination with daunorubicin (Ades 2006; Ades 2008):
First consolidation course: IV: 200 mg/m2/day for 7 days.
Second consolidation course:
Age ≤60 years and low risk (WBC <10,000/mm3): IV: 1,000 mg/m2 every 12 hours for 4 days (8 doses).
Age <50 years and high risk (WBC ≥10,000/mm3): IV: 2,000 mg/m2 every 12 hours for 5 days (10 doses).
Age 50 to 60 years and high risk (WBC ≥10,000/mm3): IV: 1,500 mg/m2 every 12 hours for 5 days (10 doses) (Ades 2008).
Age >60 years and high risk (WBC ≥10,000/mm3): IV: 1,000 mg/m2 every 12 hours for 4 days (8 doses).
Chronic lymphocytic leukemia (off-label use): OFAR regimen: IV: 1,000 mg/m2/dose over 2 hours days 2 and 3 every 4 weeks for up to 6 cycles (in combination with oxaliplatin, fludarabine, and rituximab) (Tsimberidou 2008).
Hodgkin lymphoma, relapsed or refractory (off-label use):
DHAP regimen: IV: 2,000 mg/m2 over 3 hours every 12 hours day 2 (total of 2 doses/cycle) for 2 cycles (in combination with dexamethasone and cisplatin) (Josting 2002).
ESHAP regimen: IV: 2,000 mg/m2 day 5 (in combination with etoposide, methylprednisolone, and cisplatin) every 3 to 4 weeks for 3 or 6 cycles (Aparicio 1999).
Mini-BEAM regimen: IV: 100 mg/m2 every 12 hours days 2 to 5 (total of 8 doses) every 4 to 6 weeks (in combination with carmustine, etoposide, and melphalan) (Colwill 1995; Martin 2001).
BEAM regimen (transplant preparative regimen): IV: 200 mg/m2 twice daily for 4 days beginning 5 days prior to transplant (in combination with carmustine, etoposide, and melphalan) (Chopra 1993).
Non-Hodgkin lymphomas (off-label use):
BEAM regimen (transplant-preparative regimen): IV: 200 mg/m2 twice daily for 3 days beginning 4 days prior to transplant (in combination with carmustine, etoposide, and melphalan) (Linch 2010) or 100 mg/m2 over 1 hour every 12 hours for 4 days beginning 5 days prior to transplant (in combination with carmustine, etoposide, and melphalan) (van Imhoff 2005).
Burkitt lymphoma:
CALGB 9251 regimen: Cycles 2, 4, and 6: IV: 150 mg/m2/day continuous infusion days 4 and 5 (Lee 2001; Rizzieri 2004).
CODOX-M/IVAC regimen:
Adults ≤60 years of age: Cycles 2 and 4 (IVAC): IV: 2,000 mg/m2 every 12 hours days 1 and 2 (total of 4 doses/cycle) (IVAC is combination with ifosfamide, mesna, and etoposide; IVAC alternates with CODOX-M) (Magrath 1996).
Adults ≤65 years of age: Cycles 2 and 4 (IVAC): IV: 2,000 mg/m2 over 3 hours every 12 hours days 1 and 2 (total of 4 doses/cycle) (IVAC is combination with ifosfamide, mesna, and etoposide; IVAC alternates with CODOX-M) (Mead 2008).
Adults >65 years of age: Cycles 2 and 4 (IVAC): IV: 1,000 mg/m2 over 3 hours every 12 hours days 1 and 2 (total of 4 doses/cycle) (IVAC is combination with ifosfamide, mesna, and etoposide; IVAC alternates with CODOX-M) (Mead 2008).
Hyper-CVAD alternating with high-dose methotrexate/cytarabine regimen:
Adults <60 years of age: Cycles 2, 4, 6, and 8: IV: 3,000 mg/m2 every 12 hours days 2 and 3 (total of 4 doses/cycle) of a 21-day cycle (in combination with methotrexate and leucovorin), alternating with Hyper-CVAD administered on odd-numbered cycles (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus rituximab (in cycles 1 to 4) and CNS prophylaxis (Thomas 2006).
Adults ≥60 years of age: Cycles 2, 4, 6, and 8: IV: 1,000 mg/m2 every 12 hours days 2 and 3 (total of 4 doses/cycle) of a 21-day cycle (in combination with methotrexate and leucovorin) alternating with Hyper-CVAD administered on odd-numbered cycles (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with rituximab (in cycles 1 to 4) and CNS prophylaxis (Thomas 2006).
Mantle cell lymphoma:
R-DHAP regimen: Adults ≤65 years of age: IV: 2,000 mg/m2 every 12 hours on day 2 (total of 2 doses/cycle) every 3 weeks (in combination with rituximab plus dexamethasone and cisplatin) for 4 cycles (Le Gouill 2017) or 2,000 mg/m2 every 12 hours on day 2 (total of 2 doses/cycle; in combination with rituximab plus dexamethasone and cisplatin) alternating with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) for 6 cycles (3 cycles each of R-CHOP and R-DHAP) (Hermine 2016).
RBAC regimen: IV: 500 to 800 mg/m2 over 2 hours (starting 2 hours after bendamustine) on days 2 through 4 every 28 days for up to 6 cycles (in combination with rituximab and bendamustine) (Visco 2013; Visco 2017).
Nordic regimen:
Adults ≤60 years of age: IV: 3,000 mg/m2 over 3 hours every 12 hours for a total of 4 doses (in combination with rituximab) for 2 cycles alternating with Maxi-CHOP (dose-intensified CHOP) for 3 cycles (total of 5 cycles) (Geisler 2008).
Adults >60 years of age: IV: 2,000 mg/m2 over 3 hours every 12 hours for a total of 4 doses (in combination with rituximab) for 2 cycles alternating with Maxi-CHOP for 3 cycles (total of 5 cycles) (Geisler 2008).
Hyper-CVAD alternating with high-dose methotrexate/cytarabine regimen:
Adults ≤60 years of age: Cycles 2, 4, 6, and 8: IV: 3,000 mg/m2 every 12 hours days 3 and 4 (total of 4 doses/cycle) of a 21-day cycle (in combination with methotrexate, leucovorin, and rituximab), alternating with Hyper-CVAD administered on odd-numbered cycles (cyclophosphamide, vincristine, doxorubicin, dexamethasone, and rituximab) (Romaguera 2005).
Adults >60 years of age: Cycles 2, 4, 6, and 8: IV: 1,000 mg/m2 every 12 hours days 3 and 4 (total of 4 doses/cycle) of a 21-day cycle (in combination with methotrexate, leucovorin, and rituximab) alternating with Hyper-CVAD administered on odd-numbered cycles (cyclophosphamide, vincristine, doxorubicin, dexamethasone, and rituximab) (Romaguera 2005).
Relapsed or refractory non-Hodgkin lymphomas:
DHAP regimen:
Adults ≤70 years of age: IV: 2,000 mg/m2 over 3 hours every 12 hours day 2 (total of 2 doses/cycle) every 3 to 4 weeks for 6 to 10 cycles (in combination with dexamethasone and cisplatin) (Velasquez 1988).
Adults >70 years of age: IV: 1,000 mg/m2 over 3 hours every 12 hours day 2 (total of 2 doses/cycle) every 3 to 4 weeks for 6 to 10 cycles (in combination with dexamethasone and cisplatin) (Velasquez 1988).
ESHAP regimen: IV: 2,000 mg/m2 over 2 hours day 5 every 3 to 4 weeks for 6 to 8 cycles (in combination with etoposide, methylprednisolone, and cisplatin) (Velasquez 1994).
Primary CNS lymphoma (off-label use): IV: 2,000 mg/m2 over 1 hour every 12 hours days 2 and 3 (total of 4 doses) every 3 weeks (in combination with methotrexate and followed by whole brain irradiation) for a total of 4 courses (Ferreri 2009) or 3,000 mg/m2 (maximum dose of 6,000 mg) over 3 hours on days 1 and 2 every 4 weeks for 2 cycles (administer cytarabine after 5 to 7 cycles of the induction R-MPV regimen [rituximab, methotrexate, leucovorin, vincristine, and procarbazine] and whole brain radiation therapy) (Shah 2007) or 2,000 mg/m2 over 2 hours every 12 hours days 1 to 4 (total of 8 doses) as consolidation therapy (in combination with etoposide); cytarabine/etoposide is administered following remission induction with methotrexate, leucovorin, temozolomide, and rituximab (Rubenstein 2013).
Meningeal leukemia: Intrathecal therapy: 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). Dosing provided in the manufacturer's labeling is BSA-based.
Off-label uses or doses for intrathecal therapy:
CNS prophylaxis (ALL): Intrathecal: 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 70 mg on day 1 of remission induction cycle 1 (adults <40 years of age) (Stock 2019).
or as part of intrathecal triple therapy (TIT): Intrathecal: 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 TIT): Intrathecal: 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 prophylaxis (Burkitt lymphoma; component of CODOX-M/IVAC regimen): Intrathecal: 70 mg on days 1 and 3 of cycles 1 and 3 (CODOX-M cycle) (Magrath 1996; Mead 2008).
CNS prophylaxis (Burkitt lymphoma; component of Hyper-CVAD alternating with cytarabine/methotrexate regimen): Intrathecal: 100 mg on day 7 of each 21-day treatment cycle (Thomas 2006).
CNS leukemia treatment (ALL, as part of TIT): Intrathecal: 40 mg twice weekly until CSF cleared (Storring 2009).
CNS lymphoma treatment: Intrathecal: 50 mg twice a week for 4 weeks, then weekly for 4 to 8 weeks, then every other week for 4 weeks, then every 4 weeks for 4 doses (Glantz 1999).
CNS treatment (Burkitt lymphoma; component of CODOX-M/IVAC regimen): Intrathecal: 70 mg on days 1, 3, and 5 of cycles 1 and 3 (CODOX-M cycle) and 70 mg on days 7 and 9 of cycles 2 and 4 (IVAC cycle) (Magrath 1996; Mead 2008).
Leptomeningeal metastases treatment: Intrathecal: 25 to 100 mg twice weekly for 4 weeks, then once weekly for 4 weeks, then a maintenance regimen of once a month (Chamberlain 2010) or 40 to 60 mg per dose (DeAngelis 2005).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function may increase the incidence of CNS toxicity with high-dose cytarabine treatment; use with caution and consider reduced doses. There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended:
Aronoff 2007 (cytarabine 100 to 200 mg/m2): No adjustment necessary.
Kintzel 1995 (high-dose cytarabine 1 to 3 g/m2):
CrCl 46 to 60 mL/minute: Administer 60% of dose.
CrCl 31 to 45 mL/minute: Administer 50% of dose.
CrCl <30 mL/minute: Consider use of alternative drug.
Krens 2019 (cytarabine doses ≥1 g/m2):
GFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 31 to 59 mL/minute/1.73 m2: Administer 50% of original dose.
GFR ≤30 mL/minute/1.73 m2: Use is not recommended.
Smith 1997 (high-dose cytarabine; ≥2 g/m2/dose):
Serum creatinine 1.5 to 1.9 mg/dL or increase (from baseline) of 0.5 to 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.
Romaguera 2005; Thomas 2006 (cytarabine 3 g/m2/dose [studied in Burkitt or mantle cell lymphoma]):
Serum creatinine ≥1.5 mg/dL: Reduce dose to 1 g/m2/dose.
Hemodialysis: In 4-hour dialysis sessions (with high flow polysulfone membrane) 6 hours after cytarabine 1 g/m2 over 2 hours, 63% of the metabolite ARA-U was extracted from plasma (based on a single adult case report) (Radeski 2011).
Dose may need to be adjusted in patients with liver failure since cytarabine is partially detoxified in the liver. Hepatic dysfunction may increase the incidence of CNS toxicity with high-dose cytarabine treatment; use with caution. There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended:
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.
(For additional information see "Cytarabine (conventional): Pediatric drug information")
Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. In pediatric patients, IV dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during calculations. Intrathecal dosing is based on the age of the patient. Antiemetics may be recommended to prevent nausea and vomiting. In pediatrics, a 75 mg/m2 IV dose is associated with a moderate emetic potential and IV doses ≥3,000 mg/m2 are associated with a high emetic potential (POGO [Paw Cho Sing 2019]).
Acute lymphocytic leukemia, B-cell (B-ALL):
High risk B-ALL: Limited data available, multiple regimens reported:
Vrooman 2018 (DFCI 05-001): Intensified consolidation in very high-risk patients:
Consolidation IB cycle: Children and Adolescents: IV: 75 mg/m2 once daily on days 2 through 5 and days 9 through 12 in combination with cyclophosphamide, 6-mercaptopurine, and intrathecal methotrexate (Vrooman 2018).
Consolidation IC cycle: Children and Adolescents: IV: 2,000 mg/m2 every 12 hours for 4 doses beginning on day 1; administered in combination with etoposide, dexamethasone, and asparaginase (Place 2015; Vrooman 2018).
Larsen 2016: Consolidation and delayed intensification I and II: Children and Adolescents: IV, SubQ: 75 mg/m2 over 1 to 30 minutes or subcutaneous once daily for 4 days every 7 days for 2 courses; specific days depends on protocol phase.
Steinherz 1993: NYII Protocol: Consolidation: Children and Adolescents: IV: 3,000 mg/m2 over 3 hours for 4 doses on Days 28, 29, 35, and 36; experts at some centers have suggested fewer doses (eg, 2 doses).
Isolated CNS; relapse: Limited data available; multiple regimens reported: Infants, Children, and Adolescents: IV: 300 mg/m2/dose; frequency dependent upon protocol.
Ribeiro 1995, Rivera 1996: Children and Adolescents ≤14 years: Induction: Administer on Days 8, 22, 36; for Maintenance administer every 5 weeks for 52 weeks in combination with teniposide.
Winick 1993: Continuation therapy: Infants, Children, and Adolescents: Administer on day 1 and 4 of week 7, 14, 21, 28, 35, 42, 49, and 56 in conjunction with teniposide.
Acute myeloid leukemia (AML):
Remission induction:
ADE regimen: Limited data available (Gamis 2014): Note: Some aspects of protocol dosing based on previous reports (Cooper 2012; Gibson 2011; Guest 2014; Woods 1990).
Induction 1 ADE (10 + 3 + 5) and Induction 2 ADE (8 + 3 + 5):
Infants and Children with BSA <0.6 m2: IV: 3.3 mg/kg over 1 to 30 minutes every 12 hours for 10 days (induction 1) or 8 days (induction 2) in combination with daunorubicin and etoposide.
Children and Adolescents with BSA ≥0.6 m2: IV: 100 mg/m2 over 1 to 30 minutes every 12 hours for 10 days (induction 1) or 8 days (induction 2) in combination with daunorubicin and etoposide.
7 + 3 regimen: Limited data available (Woods 1990):
Infants and Children <3 years: IV: 3.3 mg/kg/day continuous infusion for 7 days; minimum of 2 courses (in combination with daunorubicin).
Children ≥3 years and Adolescents: IV: 100 mg/m2/day continuous infusion for 7 days; minimum of 2 courses (in combination with daunorubicin).
Manufacturer's labeling: Manufacturer's labeling may not be reflective of current practice. Infants, Children, and Adolescents: IV: Standard dose: 100 mg/m2/day continuous infusion for 7 days or 200 mg/m2/day continuous infusion (as 100 mg/m2/dose over 12 hours every 12 hours) for 7 days.
Intensification: Limited data available (Gamis 2014): Note: Some aspects of protocol dosing based on previous reports (Cooper 2012; Gibson 2011; Guest 2014; Woods 1990).
Intensification 1: AE therapy.
Infants and Children with BSA <0.6 m2: IV: 33 mg/kg over 1 hour every 12 hours for 5 days (in combination with etoposide).
Children and Adolescents with BSA ≥0.6 m2: IV: 1,000 mg/m2 over 1 hour every 12 hours for 5 days (in combination with etoposide).
Intensification 2 (for patients not undergoing stem cell transplant): MA therapy:
Infants and Children with BSA <0.6 m2: IV: 33 mg/kg over 1 hour every 12 hours for 4 days (in combination with mitoxantrone).
Children and Adolescents with BSA ≥0.6 m2: IV: 1,000 mg/m2 over 1 hour every 12 hours for 4 days (in combination with mitoxantrone).
Intensification 3 (for patients not undergoing stem cell transplant):
Infants and Children with BSA <0.6 m2: IV: 99 mg/kg every 12 hours on days 1, 2, 8 and 9 in combination with E. coli L-asparaginase; Note: Some centers have substituted Erwinia asparaginase due to E. coli L-Asparaginase no longer being available.
Children and Adolescents with BSA ≥0.6 m2: IV: 3,000 mg/m2 every 12 hours on Days 1, 2, 8, and 9 in combination with E. coli L-asparaginase; Note: Some centers have substituted Erwinia asparaginase due to E. coli L-Asparaginase no longer being available.
Consolidation or refractory disease: Limited data available: Capizzi II regimen (high-dose cytarabine [fixed]): Children ≥6 years and Adolescents: IV: 3,000 mg/m2 over 3 hours every 12 hours for 4 doses, followed by E. coli L-Asparaginase (some centers have substituted Erwinia asparaginase due to E. coli L-Asparaginase no longer being available) 6 hours after the last dose of cytarabine (Capizzi 1984).
Salvage treatment for refractory/recurrent disease: Limited data available:
Clofarabine/cytarabine regimen: Children and Adolescents: IV: 1,000 mg/m2 over 2 hours once daily for 5 days (in combination with clofarabine; administer cytarabine 4 hours after initiation of clofarabine) for up to 2 induction cycles (Cooper 2014).
FLAG regimen: Children ≥11 years and Adolescents: IV: 2,000 mg/m2 over 4 hours once daily for 5 days (in combination with fludarabine and G-CSF); may repeat once if needed (Montillo 1998).
MEC regimen:
Children ≥5 years and Adolescents: IV: 1,000 mg/m2 over 6 hours for 6 days (in combination with etoposide and mitoxantrone) (Amadori 1991).
Adolescents ≥15 years: IV: 500 mg/m2/day continuous infusion days 1, 2, and 3 and days 8, 9, and 10 (in combination with mitoxantrone and etoposide); may administer a second course if needed (Archimbaud 1991; Archimbaud 1995).
Non-Hodgkin lymphomas: Limited data available:
Intermediate-risk B-cell NHL (Group B): Consolidation: R-CYM 1 and 2 regimen (Goldman 2013; Patte 2007): Children and Adolescents: IV: 100 mg/m2/day as a continuous infusion over 24 hours on Days 2 through 6 (5 days; total dose: 500 mg/m2 as a 120-hour infusion) (in combination with rituximab and methotrexate).
High-risk B-cell NHL (Group C): Consolidation: R-CYVE 1 and 2 regimen (Cairo 2007; Patte 2001): Infants ≥6 months, Children, and Adolescents: IV: 50 mg/m2 infused over 12 hours (2000 to 0800) for 5 doses (Days 1 to 5); follow each 12-hour infusion dose with 3,000 mg/m2 infused over 3 hours which starts at the end of the 12-hour infusion (0800 - 1100) x 5 doses (days 2 to 6) in combination with etoposide.
B-lineage lymphoblastic lymphoma (B-LLy) (Termuhlen 2013):
Consolidation phase: Children and Adolescents: IV, SubQ: 75 mg/m2 once daily for 4 days every 7 days for 4 courses (Days 0 to 3, 7 to 10, 14 to 17, 21 to 24).
Delayed intensification: Children and Adolescents: IV, SubQ: 75 mg/m2 once daily for 4 days every 7 days for 2 courses (Days 35 to 38 and 42 to 45).
Meningeal leukemia: Infants, Children, and Adolescents: Note: Optimal intrathecal chemotherapy dosing should be based on age (see following information) rather than on body surface area (BSA); CSF volume correlates with age and not to BSA (Bleyer 1983; Kerr 2001).
Age-based intrathecal fixed dosing: Intrathecal:
CNS prophylaxis (AML) (Woods 1990):
<1 year: 20 mg per dose.
1 to <2 years: 30 mg per dose.
2 to <3 years: 50 mg per dose.
≥3 years: 70 mg per dose.
CNS prophylaxis (ALL): Dosing regimens variable, age-specific regimens reported from literature:
Gaynon 1993: Administer on day 0 of induction therapy: Children and Adolescents:
<2 years: 30 mg per dose.
2 to <3 years: 50 mg per dose.
≥3 years: 70 mg per dose.
Pieters 2007: Administer on day 15 of induction therapy, days 1 and 15 of reinduction phase; and day 1 of cycle 2 of maintenance 1A phase: Infants and young Children (≤12 months at enrollment):
<1 year: 15 mg per dose.
≥1 year: 20 mg per dose.
Lin 2008: Administer as part of triple intrathecal therapy (TIT) 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): Infants, Children, and Adolescents:
<1 year: 18 mg per dose.
1 to <2 years: 24 mg per dose.
2 to <3 years: 30 mg per dose.
≥3 years: 36 mg per dose.
Treatment, CNS leukemia (ALL), Very high-risk: Administer as part of triple intrathecal therapy (TIT) weekly until CSF remission, then every 4 weeks throughout continuation treatment (Lin 2008): Infants, Children, and Adolescents:
<1 year: 18 mg per dose.
1 to <2 years: 24 mg per dose.
2 to <3 years: 30 mg per dose.
≥3 years: 36 mg per dose.
BSA-directed intrathecal dosing: Manufacturer's labeling (based on BSA): Manufacturer's labeling may not reflect current practice: Intrathecal: 30 mg/m2 every 4 days; range: 5 to 75 mg/m2 once daily for 4 days or once every 4 days until CNS findings normalize, followed by one additional treatment.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
IV: There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians:
Infants, Children, and Adolescents:
Standard dosing range (100 to 200 mg/m2): No adjustment necessary (Aronoff 2007)
High-dose cytarabine (1,000 to 3,000 mg/m2): There are no pediatric-specific recommendations; refer to specific protocols if available. Based on experience in adult patients, dosing adjustment suggested.
IV: Dose may need to be adjusted in patients with liver failure since cytarabine is partially detoxified in the liver. There are no dosage adjustments provided in the manufacturer's labeling (refer to protocols); however, the following guidelines have been used by some clinicians: All patients:
Floyd 2006: Transaminases (any elevation): Administer 50% of dose; may increase subsequent doses in the absence of toxicity, based primarily on experience in adult patients.
Koren 1992 (dose not specified): Bilirubin >2 mg/dL: Administer 50% of dose; may increase subsequent doses in the absence of toxicity, based on experience in adult patients.
Refer to adult dosing.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area in cytarabine dosing for hematopoietic stem cell transplant conditioning regimens (ASBMT [Bubalo 2014]).
Cytarabine/ARA-c syndrome (fever, myalgia, bone pain, occasional chest pain, maculopapular rash, conjunctivitis, and malaise and generally occurs 6 to 12 hours following cytarabine administration): May be managed with corticosteroids.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 20 mg/mL (25 mL)
Solution, Injection [preservative free]:
Generic: 20 mg/mL (5 mL, 50 mL); 100 mg/mL (20 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 20 mg/mL (5 mL, 25 mL); 100 mg/mL (1 mL, 10 mL, 20 mL)
IV: Infuse standard dose therapy for AML (100 to 200 mg/m2/day) as a continuous infusion. Infuse high-dose therapy (off-label) over 1 to 3 hours (usually). Other rates have been used, refer to specific reference.
Antiemetics may be recommended to prevent nausea and vomiting; in adults, IV doses >1,000 mg/m2 are associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Intrathecal: Intrathecal doses should be administered as soon as possible after preparation.
May also be administered SubQ.
Parenteral: Note: Antiemetics may be recommended to prevent nausea and vomiting. In pediatrics, a 75 mg/m2 IV dose is associated with a moderate emetic potential and IV doses ≥3,000 mg/m2 are associated with a high emetic potential (POGO [Paw Cho Sing 2019]).
IV infusion: May infuse as a continuous infusion over several hours (eg, 12 to 24 hours has been reported in pediatric trials) (Cairo 2007; Patte 2001). The manufacturer suggests continuous infusion of standard dose: 100 to 200 mg/m2/day. High-dose cytarabine has been infused over 1 to 3 hours according to protocols (refer to protocol) (Capizzi 1984).
IV Push: Administration over 15 to 30 minutes; has been reported in pediatric trials
SubQ: May administer at concentration not to exceed 100 mg/mL (Allwood 2003); rotate injection sites; some centers have used thigh, abdomen, and flank regions
Intrathecal administration: Antiemetic therapy should be administered prior to intrathecal doses of cytarabine. Administer as soon as possible after preparation.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute lymphoblastic leukemia: Treatment of acute lymphoblastic leukemia.
Acute myeloid leukemia: Remission induction (in combination with other chemotherapy medications) in acute myeloid leukemia in adult and pediatric patients.
Chronic myeloid leukemia: Treatment of chronic myeloid leukemia in blast phase.
Meningeal leukemia: Prophylaxis and treatment of meningeal leukemia.
Acute myeloid leukemia (consolidation); Acute myeloid leukemia (salvage); Acute promyelocytic leukemia (consolidation); Acute promyelocytic leukemia (induction); Chronic lymphocytic leukemia (refractory); Hodgkin lymphoma (relapsed or refractory); Non-Hodgkin lymphoma; Primary central nervous system lymphoma
Cytarabine may be confused with cladribine, clofarabine, Cytosar, Cytoxan, daunorubicin and cytarabine (liposomal), vidarabine, vinorelbine
Cytarabine (conventional) may be confused with cytarabine liposomal
Cytarabine (conventional) (100 mg/5 mL; Hospira manufacturer) may be confused with vinorelbine (50 mg/5 mL; Hospira manufacturer) due to similar packaging; potential for inadvertent intrathecal administration of vinorelbine may occur (ISMP [Smetzer 2015]).
Cytosar-U may be confused with cytarabine, Cytovene, Cytoxan, Neosar
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drugs classes which have a heightened risk of causing significant patient harm when used in error.
Intrathecal medication safety: The American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) chemotherapy administration safety standards (ASCO/ONS [Neuss 2016]) recommend the following safety measures for intrathecal chemotherapy:
• Intrathecal medication should not be prepared during the preparation of any other agents.
• After preparation, store in an isolated location or container clearly marked with a label identifying as "intrathecal" use only.
• Delivery to the patient should only be with other medications also intended for administration into the central nervous system.
• Administer immediately after a time-out/double-check procedure.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for IV, SUBQ, or intrathecal administration of cytarabine with concomitant chemotherapeutic agents.
Frequency not defined:
Cardiovascular: Chest pain, thrombophlebitis
Dermatologic: Alopecia, dermal ulcer, ephelis, pruritus, urticaria
Gastrointestinal: Abdominal pain, anorexia, diarrhea, esophageal ulcer, esophagitis, intestinal necrosis, nausea, oral inflammation, oral mucosa ulcer, proctocolitis, rectal ulcer, sore throat, vomiting
Genitourinary: Urinary retention
Hematologic & oncologic: Anemia, bone marrow depression, hemorrhage, leukopenia, megaloblastic anemia, reticulocytopenia, thrombocytopenia
Hepatic: Hepatic insufficiency, jaundice
Hypersensitivity: Allergic angioedema
Infection: Sepsis
Local: Cellulitis at injection site, inflammation at injection site, pain at injection site
Nervous system: Dizziness, headache, leukoencephalopathy (necrotizing), neuritis, paralysis, paraplegia
Ophthalmic: Blindness
Renal: Renal insufficiency
Respiratory: Dyspnea, pneumonia
Postmarketing (includes adverse reactions with intermediate or high dose cytarabine):
Cardiovascular: Acute myocarditis (Pallazola 2018), pericarditis (Woods 1999)
Dermatologic: Acute generalized exanthematous pustulosis (Chiu 2002), maculopapular rash (Sahu 2019), skin rash (Forghieri 2007), skin toxicity (including ear redness [red ear syndrome] and palmar-plantar erythrodysesthesia) (Sahu 2019)
Endocrine & metabolic: Hyperuricemia (Rudnick 1979)
Gastrointestinal: Increased serum amylase (Yang 2020), increased serum lipase (Yang 2020), pancreatitis (including acute pancreatitis) (Yang 2020)
Hepatic: Increased liver enzymes (Forghieri 2007)
Hypersensitivity: Anaphylaxis (Rassiga 1980)
Nervous system: Aseptic meningitis (Beaumont 2020), cerebellar syndrome (including ataxia, confusion, drowsiness, dysarthria, dysmetria, encephalitis, impaired consciousness, nystagmus disorder) (Lenfant 2021; Sainz de la Maza Cantero 2016), malaise (Sahu 2019), neurotoxicity (including peripheral neuropathy) (Malhotra 2004), reversible posterior leukoencephalopathy syndrome (Saito 2007)
Neuromuscular & skeletal: Myalgia (Sahu 2019), ostealgia (Sahu 2019), rhabdomyolysis (Truica 2002)
Ophthalmic: Conjunctivitis (Rudnick 1979), corneal toxicity (epithelial keratopathy) (Özcan 2021), keratoconjunctivitis (Cho 2018), uveitis (including anterior uveitis) (Cho 2018)
Respiratory: Pulmonary toxicity (including bronchiolitis obliterans organizing pneumonia, hypoxemia, pulmonary edema, pulmonary infiltrates) (Forghieri 2007)
Miscellaneous: Fever (Rudnick 1979)
Hypersensitivity to cytarabine or any component of the formulation
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (leukopenia, thrombocytopenia, and anemia) is the major toxicity of cytarabine. Use with caution in patients with prior drug-induced bone marrow suppression. Infection or neutropenic fever due to neutropenia or bleeding due to thrombocytopenia may occur.
• Cytarabine syndrome: Cytarabine (ARA-C) syndrome is characterized by fever, myalgia, bone pain, chest pain (occasionally), maculopapular rash, conjunctivitis, and malaise; generally occurs 6 to 12 hours following administration.
• GI toxicities: Toxicities (less serious) include nausea, vomiting, diarrhea, abdominal pain, oral ulcerations, and hepatic dysfunction.
• Hypersensitivity: Anaphylaxis resulting in acute cardiopulmonary arrest has been reported (rare).
• Pancreatitis: There have been reports of acute pancreatitis in patients receiving continuous infusion cytarabine and in patients receiving cytarabine who were previously treated with L-asparaginase.
• Sudden respiratory distress syndrome: Sudden respiratory distress, rapidly progressing to pulmonary edema and cardiomegaly, has been reported with high-dose cytarabine. May present as severe dyspnea with a rapid onset and refractory hypoxia with diffuse pulmonary infiltrates, leading to respiratory failure; may be fatal (Morgan 2011).
• Tumor lysis syndrome: Tumor lysis syndrome and subsequent hyperuricemia may occur.
Concurrent drug therapy issues:
• Drug-drug interactions: There have been case reports of fatal cardiomyopathy when high-dose cytarabine was used in combination with cyclophosphamide as a preparation regimen for transplantation.
Special populations:
• Pediatric: Delayed progressive ascending paralysis has been reported in two children who received combination chemotherapy with IV and intrathecal cytarabine at conventional doses for the treatment of acute myeloid leukemia (was fatal in one patient).
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. Benzyl alcohol is associated with gasping syndrome in premature infants.
Other warnings/precautions:
• Experienced providers: Administer under the supervision of experienced cancer chemotherapy providers. Due to the potential toxicities, induction treatment with cytarabine should be in a facility with sufficient laboratory and supportive resources.
• High-dose treatment: High-dose regimens have been associated with GI, CNS, pulmonary, ocular (reversible corneal toxicity and hemorrhagic conjunctivitis; prophylaxis with ophthalmic corticosteroids is recommended) toxicities, and cardiomyopathy. Neurotoxicity associated with high-dose treatment may present as acute cerebellar toxicity (with or without cerebral impairment), personality changes, or may be severe with seizure and/or coma; may be delayed, occurring up to 3 to 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); high-dose therapy (>18 g/m2 per cycle) and age >50 years also increase the risk for cerebellar toxicity (Herzig 1987).
• 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 also intended for administration into the CNS and administer immediately after a time-out/double-check procedure (ASCO/ONS [Neuss 2016]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Flucytosine: Cytarabine (Conventional) may diminish the therapeutic effect of Flucytosine. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who could become pregnant should avoid becoming pregnant during treatment and be advised of the potential risks if exposure during pregnancy would occur.
Based on the mechanism of action and findings from animal reproduction studies, fetal harm may occur if cytarabine is administered during pregnancy. Limb and ear defects have been noted in case reports of cytarabine exposure during the first trimester of 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 treatment can be avoided during the first trimester.
It is not known if cytarabine is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the decision to discontinue cytarabine or to discontinue breastfeeding should take into account the importance of treatment to the mother.
LFTs (periodic), CBC with differential and platelet count frequently; once blasts are no longer apparent in the peripheral blood, bone marrow should be monitored frequently, serum creatinine and BUN (periodic), serum uric acid. Monitor for signs/symptoms of bleeding, infection, neutropenic fever, and/or tumor lysis syndrome.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cytarabine inhibits DNA synthesis. Cytarabine gains entry into cells by a carrier process, and then must be converted to its active compound, aracytidine triphosphate. Cytarabine 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).
Absorption: Not effective when administered orally; less than 20% absorbed orally.
Distribution: Vd: 3 ± 11.9 L/kg; 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.
Bioavailability: SubQ: 89% to 100% (Leveque 2014).
Protein binding: 13%.
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: IV: Initial: 7 to 20 minutes; Terminal: 1 to 3 hours; Intrathecal: 2 to 6 hours.
Time to peak, plasma: SubQ: 20 to 60 minutes.
Excretion: Urine (~80%; 90% as metabolite ARA-U) within 24 hours.
Solution (Cytarabine (PF) Injection)
20 mg/mL (per mL): $1.52
100 mg/mL (per mL): $1.10 - $1.25
Solution (Cytarabine Injection)
20 mg/mL (per mL): $0.75
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