Cytosor

Approved Indications:

• Acute Myeloid Leukemia (AML):
  Induction and consolidation therapy in adults and children.
• Acute Lymphoblastic Leukemia (ALL):
  Used mainly in combination regimens, particularly for CNS prophylaxis and treatment.
• Chronic Myelogenous Leukemia (CML):
  Blast crisis phase treatment.
• Non-Hodgkin’s Lymphoma (NHL):
  Component of combination chemotherapy regimens.
• Meningeal Leukemia / CNS Leukemia:
  Intrathecal administration for prophylaxis or treatment.

Off-label/Clinically Accepted Uses:

• Lymphoblastic lymphoma
• Other hematologic malignancies as part of combination chemotherapy protocols.

Routes:

• Intravenous (IV) infusion
• Subcutaneous (SC) injection
• Intrathecal (IT) injection

Adults:

• Induction for AML:
  100–200 mg/m²/day IV continuous infusion for 7 days (7+3 regimen with anthracycline).
  Alternatively, 100–200 mg/m² IV every 12 hours for 7 days.
• Consolidation for AML:
  1–3 g/m² IV over 3 hours every 12 hours on days 1, 3, and 5 for up to 4 cycles.
• Intrathecal for CNS leukemia prophylaxis or treatment:
  12–30 mg IT once or twice weekly depending on protocol.
• Subcutaneous administration:
  Typically 20–40 mg/m² twice daily for 5 days in low-dose regimens.

Pediatrics:
Dosing based on body surface area; similar regimens as adults with weight-based adjustments.

Elderly:
Dose reduction may be necessary depending on tolerance and organ function.

Renal/Hepatic Impairment:
No specific dose adjustment established; monitor closely.

Administration Notes:

• Intrathecal dosing requires strict aseptic technique.
• Hydration recommended to prevent renal toxicity.
• Co-administration with corticosteroids may reduce ara-C toxicity.

Cytarabine is a pyrimidine nucleoside analog that, after cellular uptake, is phosphorylated to its active triphosphate form, cytarabine triphosphate (ara-CTP). Ara-CTP competitively inhibits DNA polymerase during DNA synthesis and incorporates into DNA, causing premature chain termination and inhibition of DNA replication. This mechanism leads to S-phase specific cytotoxicity, mainly affecting rapidly dividing malignant hematopoietic cells.

• Absorption: Not absorbed orally; parenteral administration required.
• Distribution: Widely distributed; crosses blood-brain barrier and placenta.
• Protein Binding: Minimal.
• Metabolism: Rapidly deaminated by cytidine deaminase in liver, kidney, and blood to inactive metabolite, uracil arabinoside (ara-U).
• Half-life: Approximately 10 minutes after IV bolus; extended to 2–3 hours after continuous infusion.
• Elimination: Primarily renal excretion of inactive metabolites.

• Pregnancy: Category D. Cytarabine is teratogenic and embryotoxic; contraindicated in pregnancy unless benefits clearly outweigh risks.
• Lactation: Excreted in breast milk; breastfeeding not recommended due to potential toxicity.
• Recommendation: Avoid use during pregnancy and breastfeeding unless under strict medical supervision.

• Primary Class: Antimetabolite Chemotherapy Agent
• Subclass: Pyrimidine Analog (S-phase specific)

• Known hypersensitivity to cytarabine or any component of the formulation.
• Severe bone marrow suppression unrelated to malignancy.
• Active severe infections without appropriate treatment.
• Pregnancy and lactation unless absolutely necessary.

• Myelosuppression: Severe neutropenia, thrombocytopenia, and anemia are common; monitor CBC frequently.
• Neurotoxicity: Intrathecal administration may cause arachnoiditis, chemical meningitis, seizures.
• Pulmonary toxicity: Risk of interstitial pneumonitis and pulmonary edema.
• Hepatotoxicity: Elevated liver enzymes and rare hepatic failure.
• Renal impairment: Monitor renal function; dose adjustments may be needed.
• Gastrointestinal toxicity: Mucositis, nausea, vomiting.
• Monitor for early signs of infection due to immunosuppression.

Common:

• Hematologic: Neutropenia, thrombocytopenia, anemia
• Gastrointestinal: Nausea, vomiting, mucositis, diarrhea
• Neurologic: Headache, dizziness, confusion (especially with IT use)
• Dermatologic: Rash

Serious/Rare:

• Cerebellar toxicity (ataxia, dysarthria) with high doses
• Chemical arachnoiditis (intrathecal use)
• Pulmonary fibrosis
• Hepatic veno-occlusive disease (rare)

• Drugs increasing myelosuppression: Other chemotherapeutics, radiation therapy.
• Allopurinol: May increase cytarabine toxicity.
• Live vaccines: Contraindicated due to immunosuppression.
• Enzyme Systems: Not primarily CYP450 metabolized; interaction potential is low but co-administered drugs affecting bone marrow require caution.

• Current AML treatment guidelines recommend high-dose cytarabine as consolidation in eligible patients.
• Intrathecal cytarabine remains standard for CNS leukemia prophylaxis.
• Newer liposomal formulations under investigation for improved delivery and reduced toxicity.
• Guidelines emphasize dose adjustments in elderly and patients with comorbidities to reduce toxicity.

• Store injectable solution at 20°C to 25°C (68°F to 77°F).
• Protect from light and freezing.
• Do not shake vial; use aseptic technique.
• Use immediately after reconstitution; discard unused portions.