Article: Fludarabine

Fludarabine
Systematic (IUPAC) name
[(2R,3R,4S,5R)-5- (6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Identifiers
CAS number	75607-67-9
ATC code	L01BB05
PubChem	30751
DrugBank	APRD00594
Chemical data
Formula	C10H13FN5O7P
Mol. weight	365.212 g/mol
Pharmacokinetic data
Bioavailability	55%
Protein binding	19-29%
Metabolism	?
Half life	20 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D
Legal status	?(AU) POM(UK)
Routes	Intravenous, Oral

Fludarabine (Fludara®) is a chemotherapy drug used in the treatment of hematological malignancies.

Indications

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone.^[1] Fludarabine is used in various combinations with cyclophosphamide, mitoxantrone, dexamethasone and rituximab in the treatment of indolent non-Hodgkins lymphomas. As part of the FLAG regimen, fludarabine is used together with cytarabine and granulocyte colony-stimulating factor in the treatment of acute myeloid leukaemia. Because of its immunosuppressive effects, fludarabine is also used in some conditioning regimens prior to non myeloablative allogeneic stem cell transplant.

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.

Side effects

Fludarabine is associated with profound lymphopenia, and as a consequence, increases the risk of opportunistic infections significantly. Patients who have been treated with fludarabine will usually be asked to take co-trimoxazole or to use monthly nebulised pentamidine to prevent pneumocystis carinii pneumonia. The profound lymphopenia caused by fludarabine renders patients susceptible to transfusion-associated graft versus host disease, a 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.^[2]

Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.^[3]