Fludarabine

Source: Wikipedia, the free encyclopedia.
Fludarabine
by mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability55%
Protein binding19 to 29%
Elimination half-life20 hours
ExcretionKidney
Identifiers
  • (2R,3S,4S,5R)-2-(6-amino-2-fluoropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
JSmol)
SMILES
  • Fc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)[C@@H]3O)CO)N
  • InChI=1S/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/m1/s1 checkY
  • Key:HBUBKKRHXORPQB-FJFJXFQQSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Fludarabine is a purine analogue and antineoplastic agent. It is generally used as its 5-O-phosphorylated form known as fludarabine phosphate, sold under the brand name Fludara among others. It is a

injection into a vein or by mouth.[3]

Common side effects include nausea,

purine analog family of medications and works by interfering with the duplication of DNA.[3][4]

Fludarabine was approved for medical use in the United States in 1991.[3] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone.[6] Fludarabine is used in various combinations with

allogeneic stem cell transplant
.

Side effects

Fludarabine is associated with profound

transfusion-associated graft versus host disease, an oftentimes fatal complication of blood transfusion. For this reason, all patients who have ever received fludarabine should only be given irradiated
blood components.

Fludarabine causes anemia, thrombocytopenia and neutropenia, requiring regular blood count monitoring. Some patients require blood and platelet transfusion, or G-CSF injections to boost neutrophil counts.

Fludarabine is associated with the development of severe autoimmune hemolytic anemia in a proportion of patients.[7]

Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.[8]

Pharmacology

Fludarabine is a

purine analog, and can be given both orally and intravenously. Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase
. It is active against both dividing and resting cells. Being phosphorylated, fludarabine is ionized at physiologic pH and is effectually trapped in blood. This provides some level of specificity for blood cells, both cancerous and healthy.

History

Fludarabine was produced by John Montgomery and Kathleen Hewson of the

Southern Research Institute in 1968.[9]

Names

Fludarabine is generally administered as its 5-O-phosphorylated form known as fludarabine phosphate, which is rapidly dephosphorylated to fludarabine in the plasma.

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  3. ^ a b c d e f g h "Fludarabine Phosphate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. ISBN 9780781757348. Archived
    from the original on 2016-12-20.
  5. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. PMID 11114313
    .
  7. PMID 9698219
    .
  8. PMID 12969985
    .
  9. ISBN 0-471-89979-8
    .
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