CYTARABINE 
Pronounciation
- (sye-TAIR-ah-bean)
Trade Name(s)
- ARA-C, Cytosar
, Cytosar-U
Verify pregnancy status. Baseline studies indicated; see Monitor.
Dose is variable depending on specific regimen or protocol. Consult guidelines for current treatment regimens.
Acute nonlymphocytic leukemia in adult and pediatric patients:
Manufacturer lists a dose of 100 mg/M2/24 hr as a continuous infusion or 100 mg/M2 as an IV injection every 12 hours. Repeat daily on Days 1 through 7.
Acute myelocytic leukemia or erythroleukemia in adult and pediatric patients:
Manufacturer lists a dose of 100 mg/M2/24 hr as a continuous infusion or 200 mg/M2/day continuous infusion (as 100 mg/M2 over 12 hours every 12 hours) for 7 days.
Dose reduction may be indicated in impaired hepatic or renal function. ■ See Precautions/Monitor. ■ Usually used with other antineoplastic drugs in specific doses to achieve tumor remission. ■ Withhold or modify dose based on degree of bone marrow suppression; see Monitor.
Specific techniques required; see Precautions.
Available in multiple concentrations. Read label carefully. May be given by IV injection as is or further diluted in NS or D5W and given as an infusion. Use only clear solutions.
Store unused vials at CRT in carton to protect from light. When infusion solutions are prepared in D5W or NS, 94% to 96% of cytarabine remains present after 8 days. Immediate use preferred.
Compatibility information not available from manufacturer. Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Each 100 mg or fraction thereof over 15 to 30 minutes. When large IV doses are given too quickly, patients are frequently nauseated and may vomit for several hours postinjection. This problem tends to be less severe when the drug is infused.
Single daily dose properly diluted over 30 minutes to 24 hours, depending on amount of infusion solution and dosage regimen.
An antimetabolite that inhibits synthesis of DNA. Cell-cycle specific for S phase. It is a pyrimidine analog that is incorporated into DNA. It inhibits DNA polymerase, resulting in decreased DNA synthesis and repair. Through various chemical processes this deprivation acts more quickly on rapidly growing cells and causes their death. A potent bone marrow suppressant. Crosses the blood-brain barrier. Serum half-life averages 1 to 3 hours. Metabolized in the liver and excreted in the urine.
Used in combination with other approved anticancer drugs for remission induction in acute nonlymphocytic leukemia in adults and pediatric patients. Also used for treatment of acute lymphocytic leukemia (ALL), the blast phase of chronic myelocytic leukemia, and acute myelocytic leukemia (AML). ■ Is used intrathecally in the treatment of meningeal leukemia. A liposomal formulation (DepoCyt) is available for intrathecal use only; lipofoam molecules contained in this product are much too large for IV use.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Administered by or under the direction of a physician specialist in a facility with adequate diagnostic and treatment facilities to monitor the patient and respond to any medical emergency. Must be able 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. Complications of bone marrow suppression include infection resulting from granulocytopenia and hemorrhage secondary to thrombocytopenia. Use with caution in patients with pre-existing drug-induced bone marrow suppression. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and hepatic dysfunction. Weigh benefit versus risk of known toxic effects before initiating therapy.■ Remissions induced by cytarabine are brief unless followed by maintenance therapy. ■ Severe, and sometimes fatal, GI, pulmonary, cardiac, or CNS toxicity has occurred with experimental cytarabine regimens. Toxicities are different (e.g., reversible corneal toxicity, hemorrhagic conjunctivitis, cerebral and cerebellar dysfunction, severe GI ulceration) from those seen with conventional therapy. Deaths have been reported. ■ Cases of cardiomyopathy and a syndrome of sudden respiratory distress rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly have been reported following experimental high-dose therapy. ■ Do not use product containing benzyl alcohol if experimental high-dose therapy is administered. ■ Use with caution and possibly at reduced doses in patients with renal or hepatic impairment. ■ May induce hyperuricemia (tumor lysis syndrome) secondary to rapid lysis of neoplastic cells. ■ Acute pancreatitis has been reported in patients receiving cytarabine by continuous infusion and in patients being treated with cytarabine who have had prior treatment with L-asparaginase.
Leukocyte and platelet counts should be monitored daily. ■ During induction therapy, WBC depression is biphasic with the first nadir occurring at Days 7 to 9 and a deeper fall at Days 15 to 24. Platelet depression begins around Day 5 and reaches a nadir at Days 12 to 15. ■ Hold or modify therapy for platelet count less than 50,000 or polymorphonuclear granulocytes less than 1,000 cells/mm3. Counts may continue to fall after the drug is stopped and may reach lowest values after drug-free intervals of 12 to 14 days. Restart therapy when bone marrow recovery is confirmed. Patients whose drug is withheld until “normal” peripheral blood values are attained may escape from control. ■ Monitor hepatic and renal function at regular intervals during therapy. ■ Perform bone marrow examinations frequently after blasts have disappeared from the peripheral blood. ■ Higher total doses tolerated by IV injection compared with IV infusion, but the incidence and intensity of nausea and vomiting are increased. ■ Prophylactic administration of antiemetics recommended. ■ Be alert for signs of bone marrow suppression, bleeding, infection, or neurotoxicity. These side effects are dose- and schedule-dependent. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood). ■ Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Monitor uric acid levels and maintain hydration; allopurinol may be indicated. ■ Monitor for S/S of pancreatitis (e.g., elevated amylase, nausea, vomiting, upper abdominal pain).
Effective birth control recommended. ■ SeeAppendix D, p. 1311. ■ Promptly report early signs of neurotoxicity (e.g., ataxia, confusion, lethargy) or bone marrow suppression (e.g., infection, bleeding).
Avoid pregnancy. Can cause fetal harm when administered to a pregnant woman, especially during the first trimester. ■ Discontinue breast-feeding. ■ Benzyl alcohol may cause a fatal “gasping syndrome” in premature infants. ■ See Drug/Lab Interactions.
Consider age-related organ impairment; toxicity may be increased.
May inhibit digoxin absorption. ■ Do not administer any live virus vaccines to patients receiving antineoplastic drugs. ■ May cause acute pancreatitis in patients who previously received L-asparaginase.■ May antagonize action of gentamicin against Klebsiella. ■ May antagonize antifungal actions of flucytosine.
Abdominal pain, anorexia, bleeding, bone marrow suppression (e.g., anemia, leukopenia, thrombocytopenia), bone pain, cardiomyopathy, chest pain, conjunctivitis, diarrhea, esophagitis, fever, hepatic dysfunction, hypersensitivity reactions, hyperuricemia, malaise, megaloblastosis, mucosal bleeding, myalgia, nausea, oral and anal ulceration, pancreatitis, peripheral motor and sensory neuropathies, rash, stomatitis, thrombophlebitis, vomiting. Higher than usual dose regimens may cause severe coma, GI ulcerations and peritonitis, personality changes, pulmonary toxicity, somnolence, or death.
Notify the physician of all side effects. Most will be treated symptomatically. Some toxicity is necessary to produce remission. Discontinue or withhold the drug for serious bone marrow suppression. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa [Aranesp], epoetin alfa [Epogen], filgrastim [Neupogen, Zarxio], pegfilgrastim [Neulasta], sargramostim [Leukine]) may be indicated to treat bone marrow toxicity. Drug must be restarted as soon as signs of bone marrow recovery occur, or its effectiveness will be lost. Use corticosteroids for cytarabine syndrome (fever, myalgia, bone pain, occasional chest pain, maculopapular rash, conjunctivitis, malaise). Usually occurs in 6 to 12 hours after administration. Continue cytarabine if patient responds to corticosteroids. There is no specific antidote; supportive therapy as indicated will help to sustain the patient in toxicity.