Adult Dosing

AML

Remission induction

• 100 mg/m²/day IV as continuous infusion x 7 days
• Alt: 100 mg/m²/day IV q12 hrs x 7 days

ALL

Remission induction

• 100-200 mg/m²/day or 2-6 mg/kg/day as a continuous IV infusion over 24 hrs or in divided doses by rapid injection for 5-10 days
• Repeat courses q2 weeks

Maintenance therapy

• 1 mg/kg/dose SC 1-2 times/wk
• Alt: 70-200 mg/m² IV for 2-5 days repeated every month

Acute nonlymphocytic leukemia (combination with other chemotherapeutic agents)

• 100 mg/m² continuous IV on days 1 through 7 or 100 mg/m² IV q12 hrs for 7 days
• ALT: 10 mg/m² SC bid for 7-14 days in combination with other chemotherapeutic agents

Refractory acute leukemias

• 2-3 g/m² IV q12 hrs for 2-6 days

Meningeal leukemia

• 30 mg/m² IT q4 days
• ALT: 5-75 mg/m² IT q1-4 days
• Note: Dose varies with the type of CNS symptoms and previous therapy

Acute promyelocytic leukemia [Non-FDA Approved]

• For induction therapy with ATRA (tretinoin) and daunorubicin
• 200 mg/m² IV on days 1-7

• For consolidation-2 x cycles:
• 200mg/m² IV for 7 days
• 1g/m² IV q12h x 8 doses

• Note: 2g/m² q12h x 8 doses-has been used in higher risk patients

Pediatric Dosing

AML

Remission induction

• 100 mg/m²/day IV as continuous infusion x 7 days
• Alt: 100 mg/m²/day IV q12 hrs x 7 days

ALL

Remission induction

• 100-200 mg/m²/day as a continuous IV infusion over 24 hrs or in divided doses by rapid injection for 5-10 days
• Repeat courses q2 weeks

Maintenance therapy

• 1.5 mg/kg/dose SC/IM q1-4 wks

Acute nonlymphocytic leukemia (combination with other chemotherapeutic agents)

• 100 mg/m² continuous IV on days 1 through 7 or 100 mg/m² IV q12 hrs for 7 days

Refractory acute leukemias

• 1-3 g/m² IV q12 hrs for 2-6 days

Meningeal leukemia

• 30 mg/m² IT q4 days
• ALT: 5-75 mg/m² IT q1-4 days
• Note: Dose varies with the type of CNS symptoms and previous therapy

Acute promyelocytic leukemia [Non-FDA Approved]

• Usage is still controversial but above doses have been used in children <18 in some trials

[Outline]

• Adult Dosing
• Pediatric Dosing

• Remission induction in acute non-lymphocytic leukemia of adults and pediatric patients
• Treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia
• Prophylaxis and treatment of meningeal leukemia

• Hypersensitivity to any of the ingredients of the product
• Neonates (benzyl alcohol-containing INJ forms)

• Only physicians experienced in cancer chemotherapy should use cytarabine
• For induction therapy, treat patients 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 is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and hepatic dysfunction
• Weigh benefit risk ratio before considering therapy with cytarabine. Physician should be familiar w/ complete prescribing information before use

Renal Dose Adjustment

• Renal impairment: Caution advised; consider reducing dose, dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Caution advised; consider reducing dose, dose adjustments not defined

• Cytarabine is a potent bone marrow suppressant. Use cautiously in patients with pre-existing drug-induced bone marrow suppression. During induction therapy, perform leukocyte and platelet counts daily. Perform bone marrow examinations frequently after blasts have disappeared from the peripheral blood
• Discontinue or modify therapy when drug-induced marrow depression results in a platelet count < 50,000/mm^3, or a polymorphonuclear granulocyte count < 1,000/mm^3,
• One case of anaphylaxis has occurred resulting in acute cardiopulmonary arrest which required resuscitation. This occurred immediately after IV administration
• Severe and at times fatal CNS, GI and pulmonary toxicity has been reported. Patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose
• Cases of cardiomyopathy with subsequent death have been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide
• Cytarabine can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant
• Monitor patients receiving high doses for neurotoxicity dysfunction
• Monitor CBC with differential counts qd
• Monitor BUN/creatinine, LFTs, bone marrow exams and serum uric acids frequently

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Concurrent neurotoxic drugs
• Concurrent cytotoxic drugs
• Myelosuppression
• Decreased bone marrow reserve
• Chronic debilitating illnesses
• Women with childbearing potential

Pregnancy Category:D

Breastfeeding: Safety unknown. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

• HEMA: Anemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes
• GI: Anorexia, nausea, vomiting, diarrhea, hepatitis, hepatotoxicity, severe GI ulceration (high dose), stomatitis. pancreatitis, esophagitis, esophageal ulceration, anal ulceration
• CNS: CNS dysfunction (high dose), confusion, drowsiness, headache, neuritis, neural toxicity, paraplegia (IT) leukoencephalopathy, necrotizing (IT) blindness (IT)
• CV: Chest pain, pericarditis
• METABOLIC: Hyperuricemia
• DERM: Alopecia, rash, urticaria, skin ulceration, pruritis
• GU: Urinary retention, renal dysfunction,
• EENT: Corneal toxicity (high dose), hemorrhagic conjunctivitis (high dose)
• RESP: Pneumonia, pulmonary edema (high dose), shortness of breath
• LOCAL: Inj site cellulitis, thrombophlebitis
• MISC: Infection, fever, sepsis, bleeding, anaphylaxis, angioedema

• Cytarabine is a pyrimidine analog, it inhibits DNA synthesis by inhibiting DNA polymerase (cell-cycle S-phase–specific)
• Metabolized mostly by the liver
• Renally Excreted (80%)
• Half-Life: 1–3 hrs (IV, SC); 100-236 hrs (IT)

US Trade Name(s)

• Cytosar-U

US Availability

cytarabine (generic)

• INJ: 100 mg/vial
• INJ: 500 mg/vial
• INJ: 1 g/vial
• INJ: 2 g/vial
• INJ: 20 mg/mL
• INJ: 100 mg/mL

Cytosar-U

• INJ: 100 mg/vial
• INJ: 500 mg/vial
• INJ: 1 g/vial
• INJ: 2 g/vial

Canadian Trade Name(s)

• Only generic available

Canadian Availability

cytarabine (generic)

• INJ: 100 mg/vial
• INJ: 500 mg/vial
• INJ: 1 g/vial
• INJ: 2 g/vial
• INJ: 100 mg/mL

UK Trade Name(s)

• Only generic available

UK Availability

cytarabine (generic)

• INJ: 20 mg/mL (5, 25, 50 mL vials)
• INJ: 100 mg/mL (1, 5, 10, 20 mL vials)

Australian Trade Name(s)

• Only generic available

Australian Availability

cytarabine (generic)

• INJ: 100 mg/5 mL
• INJ: 500 mg/25 mL
• INJ: 1000 mg/10 mL
• INJ: 2000 mg/20 mL

[Outline]

Hematology/Oncology

Antineoplastics

Antimetabolites