Cytarabine

Myelosuppression (leukopenia, thrombocytopenia and anemia) is the major toxicity of cytarabine. Use with caution in patients with prior drug-induced bone marrow suppression. Monitor blood counts frequently; once blasts are no longer apparent in the peripheral blood, bone marrow should be monitored frequently. Monitor for signs of infection or neutropenic fever due to neutropenia or bleeding due to thrombocytopenia.

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. May be managed with corticosteroids.

Toxicities (less serious) include nausea, vomiting, diarrhea, abdominal pain, oral ulcerations and hepatic dysfunction. In adults, doses >1000 mg/m2 are associated with a moderate emetic potential (Hesketh 2017; Roila 2016). In pediatrics, doses >200 mg/m2 are associated with a moderate emetic potential and 3000 mg/m2 is associated with a high emetic potential (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting.

Anaphylaxis resulting in acute cardiopulmonary arrest has been reported (rare).

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, 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 and subsequent hyperuricemia may occur; consider antihyperuricemic therapy and hydrate accordingly. Disease-related concerns:

Use with caution in patients with hepatic impairment; may be at higher risk for CNS toxicities and dosage adjustments may be required.

Use with caution in patients with impaired renal function (high dose cytarabine); may be at higher risk for CNS toxicities and dosage adjustments may be required. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. 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:

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:

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:

Should be administered under the supervision of an experienced cancer chemotherapy physician. Due to the potential toxicities, induction treatment with cytarabine should be in a facility with sufficient laboratory and supportive resources.

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).

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 central nervous system (Jacobson 2009).