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Fludarabine Phosphate (FLUDARABINE)
Fludarabine works by interfering with DNA synthesis, thereby inhibiting cancer cell growth and proliferation.
Fludarabine Phosphate, also known as fludarabine, is a small molecule medication originally developed by Fresenius Kabi USA and currently owned by Genzyme Corp. It is FDA-approved for the treatment of B-cell chronic lymphocytic leukemia (CLL). As an off-patent medication, fludarabine is available from multiple generic manufacturers. Key safety considerations include potential bone marrow suppression and increased risk of infections. Commercially, fludarabine is widely available in the market.
At a glance
| Generic name | FLUDARABINE |
|---|---|
| Sponsor | Genzyme Corp |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2007 |
Mechanism of action
Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Approved indications
- B-cell chronic lymphocytic leukemia (CLL)
Boxed warnings
- WARNING: SEVERE BONE MARROW SUPPRESSION, CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY Fludarabine Phosphate Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Fludarabine phosphate injection can severely suppress bone marrow function. When used at high doses in dose-ranging studies in patients with acute leukemia, fludarabine phosphate was associated with severe neurologic effects, including blindness, coma, and death. This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m 2 /day for 5 to 7 days) than the recommended dose. Similar severe central nervous system toxicity, including coma, seizures, agitation and confusion, has been reported in patients treated at doses in the range of the dose recommended for chronic lymphocytic leukemia [see Warnings and Precautions ( 5.2 )] . Instances of life-threatening and sometimes fatal autoimmune phenomena such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evans syndrome, and acquired hemophilia have been reported to occur after one or more cycles of treatment with Fludarabine Phosphate Injection. Patients undergoing treatment with Fludarabine Phosphate Injection should be evaluated and closely monitored for hemolysis [see Warnings and Precautions ( 5.3 )]. In a clinical investigation using fludarabine phosphate in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL), there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of Fludarabine Phosphate Injection in combination with pentostatin is not recommended [see Warnings and Precautions ( 5.5 )]. WARNING: CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY See full prescribing information for complete boxed warning. Severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m 2 /day for 5 to 7 days) than the recommended dose. This toxicity was seen in ≤0.2% of patients treated at the recommended dose levels (25 mg/m 2 ). ( 5.1 ) Instances of life-threatening and sometimes fatal autoimmune hemolytic anemia have been reported after one or more cycles of treatment. ( 5.3 ) In a clinical investigation of the combination of fludarabine phosphate with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL), there was an unacceptably high incidence of fatal pulmonary toxicity. ( 5.5 )
Common side effects
- Myelosuppression
- Fever
- Infection
- Nausea
- Vomiting
- Fatigue
- Anorexia
- Cough
- Weakness
- Pneumonia
- Pulmonary hypersensitivity reactions
- Edema
Drug interactions
- Pentostatin
- Pentostatin
Key clinical trials
- Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant (PHASE1)
- Dual-Target GPC3/B7-H3 CAR-NK Cells for Advanced HCC (PHASE1,PHASE2)
- Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL (PHASE1,PHASE2)
- MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial) (PHASE2)
- Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies (PHASE1)
- Dual-Target GD2/B7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma (PHASE1,PHASE2)
- Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID) (PHASE2)
- Venetoclax or Placebo in Combination With Reduced-Intensity Conditioning Hematopoietic Cell (Bone Marrow/Blood Stem Cell) Transplant and as Maintenance Therapy After Transplant in Patients With Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial) (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Fludarabine Phosphate CI brief — competitive landscape report
- Fludarabine Phosphate updates RSS · CI watch RSS
- Genzyme Corp portfolio CI