Fludarabine (Fludara)

General information

Class/mechanism: Purine analog, antimetabolite; fludarabine is converted to the active compound, 2-fluoro-ara-ATP, which inhibits DNA synthesis by inhibiting DNA polymerase alpha, ribonucleotide reductase, and DNA primase. Relatively resistant to deamination by adenosine deaminase. The mechanism of action is not completely characterized and may be multi-faceted.
Route: IV, PO Note: Oral fludarabine is no longer available in the US, at this time.
Extravasation: neutral

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.

Diseases for which it is established (work in progress)

• Acute myeloid leukemia (PMDA)
  • Acute myeloid leukemia, FLT3-positive
• Chronic lymphocytic leukemia (FDA, PMDA)
• Indolent lymphoma (PMDA)
  • Follicular lymphoma
  • Marginal zone lymphoma
  • Waldenström macroglobulinemia
• Mantle cell lymphoma (PMDA)

Scenarios for which it is established

• Allogeneic HSCT conditioning regimens (PMDA)
• Cellular therapy conditioning regimens (PMDA)

Diseases for which it is used

• Anaplastic large cell lymphoma
• B-cell acute lymphoblastic leukemia
• B-cell lymphoma of mucosa-associated lymphoid tissue
• Cold agglutinin disease
• Diffuse large B-cell lymphoma
• Classical Hodgkin lymphoma
• NK- and T-cell lymphoma
• Peripheral T-cell lymphoma
• Primary mediastinal B-cell lymphoma
• Transformed lymphoma

Diseases for which it was used

• Multiple myeloma
• Renal cell carcinoma

Patient drug information

• Fludarabine (Fludara) package insert
• Fludarabine (Fludara) patient drug information (Chemocare)
• Fludarabine (Fludara) patient drug information (UpToDate)

History of changes in FDA indication

• 1991-04-18: Initial FDA approval for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen. (Based on Grever et al. 1990 & Keating et al. 1989)
• 2024-11-19: Project Renewal revision as a component of a combination regimen for the treatment of adults with B-cell chronic lymphocytic leukemia (CLL). (Based on GCLLSG CLL8, REACH)
• 2024-11-19: Project Renewal revision for the treatment of adults with B-cell CLL who have not responded to or whose disease has progressed during treatment with at least one alkylating-agent containing regimen.

History of changes in EMA indication

• 1994-08-11: EURD

History of changes in PMDA indication

• 2007-01-26: New route of administation and additional indications for treatment of low-grade B-cell non-Hodgkin lymphoma and mantle cell lymphoma.
• 2008-05-20: New indication and a new dosage for use as a conditioning prior to allogeneic hematopoietic stem cell transplantation in the following diseases: acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, chronic lymphocytic leukemia, malignant lymphoma, and multiple myeloma.
• 2009-11-06: New additional indication for the treatment of chronic lymphocytic leukemia with anemia or thrombocytopenia.
• 2009-11-06: New additional indications and a new dosage for the treatment of recurrent or refractory low-grade B-cell non-Hodgkin’s lymphoma and mantle cell lymphoma.
• 2019-03-26: New indication for the treatment prior to tumor-specific T-cell infusion therapy.
• 2022-06-20: New indication and a new dosage for the treatment of relapsed or refractory acute myeloid leukemia.

Also known as

• Generic names: FAMP, fludarabine phosphate
• Brand names: Beneflur, Fludabine, Fludara, Lymfuda, Oforta