Class: Purine nucleoside analog (antimetabolite)
Mechanism of Action
- Inhibits DNA synthesis by incorporating into DNA and inhibiting DNA polymerase, ribonucleotide reductase, and DNA primase → causes chain termination and apoptosis
- Immunosuppressive effects by inhibiting T- and B-lymphocyte function
Indications
- Chronic Lymphocytic Leukemia (CLL) (especially relapsed or refractory)
- Low-grade Non-Hodgkin Lymphoma (NHL)
- Sometimes used off-label in conditioning regimens before stem cell transplant
Dosing
- Common adult dose: 25 mg/m² IV daily × 5 days every 28 days
- Oral formulations available but less common
- Dose adjustment required in renal impairment
Key Adverse Effects
- Myelosuppression: neutropenia, anemia, thrombocytopenia (dose-limiting)
- Immunosuppression: increased risk of opportunistic infections (e.g., PCP, fungal)
- Neurotoxicity: rare but severe (visual disturbances, confusion, seizures)
- Autoimmune hemolytic anemia and other autoimmune phenomena
- Nausea, fatigue, fever, rash
Monitoring
- CBC with differential regularly (especially neutrophils)
- Renal function before and during treatment (dose adjust if impaired)
- Signs of infection; consider PCP prophylaxis
- Neurologic assessment if symptoms develop
Supportive Care
- PCP prophylaxis recommended during and after treatment
- Infection monitoring and prompt treatment
- Dose reductions or delays for hematologic toxicity
Other Important Notes
- Synergistic with cyclophosphamide and rituximab (FCR regimen in CLL)
- Watch for tumor lysis syndrome in high tumor burden
- Can cause prolonged lymphopenia lasting months post-treatment