Fludarabine
Mechanism :
Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.
Indication :
- Chronic lymphocytic leukemia
- Acute leukemia
- Solid tumors
Contraindications :
Hypersensitivity, Concomitant pentostatin: risk of fatal pulmonary toxicity, Severe renal impairment.
Dosing :
Usual Pediatric Dose for Malignant Disease:
Solid tumors: 7 to 9 mg/m² IV bolus followed by 20 to 27 mg/m²/day continuous IV infusion for 5 days.
Usual Pediatric Dose for Leukemia:
Acute leukemia: 10 mg/m² IV once over 15 minutes followed by continuous IV infusion of 30.5 mg/m²/day for 5 days or 10.5 mg/m² IV once over 15 minutes followed by continuous IV infusion of 30.5 mg/m²/day for 2 days followed by
cytarabine.
Usual Pediatric Dose for Stem Cell Transplant Conditioning:
Reduced-intensity conditioning regimen prior to allogenic hematopoietic stem cell transplantation: 30 mg/m²/day for 5 days.
Usual Adult Dose for Chronic Lymphocytic Leukemia:
IV: 25 mg/m² IV once over 30 minutes for 5 days every 28 days. Following a maximal tumor response, 3 additional cycles are recommended.
Oral: 40 mg/m² once daily for 5 days every 28 days.
Usual Adult Dose for non-Hodgkin’s Lymphoma:
25 mg/m²/day for 5 days every 28 days.
Adverse Effect :
Serious Reactions: Neurotoxicity, myelosuppression, pancytopenia, autoimmune hemolytic anemia, tumor lysis syndrome, pulmonary toxicity, pneumonia, opportunistic infection, hypersensitivity reactions, stomatitis, GI bleeding, hemorrhagic cystitis.
Common Reactions: Neutropenia, thrombocytopenia, anemia, fever, rigors, infection,
nausea/vomiting, malaise, fatigue, anorexia, weakness, dyspnea, cough, diaphoresis,
edema, rash.
Interaction :
Dipyridamole: May decrease the effect of fludarabine.
Pentostatin: Unacceptable pulmonary toxicity.
Trastuzumab: May increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 30-70 | 50–75% of normal dose |
| 10-30 | 50–75% of normal dose. Use with care |
| <10 | 50% of normal dose. Use with care |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–30 mL/min |
Hepatic Dose :
No dosage adjustment is recommended.