Fludarabine

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.

• Fludarabine Phosphate Injection is a nucleotide metabolic inhibitor indicated for: The treatment of adult 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. Benefit in treatment-naïve or non-refractory CLL patients is not established.ICD-10: C95.90

• None Nonecontraindicated

The recommended adult dose is 25 mg/m 2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5 day course of treatment should commence every 28 days. ( 2.1 ) Reduce dose in patients with creatinine clearance 30 to 70 mL/min/l.73 m 2 . Do not use in patients with severe renal impairment ( 2.2 ). 2.1 Recommended Dose The recommended adult dose of fludarabine phosphate injection is 25 mg/m 2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5-day course of treatment should commence every 28 days. Dosage may be decreased or delayed based on evidence of hematologic or nonhematologic toxicity. Physicians should consider delaying or discontinuing the drug if neurotoxicity occurs. A number of clinical settings may predispose to increased toxicity from Fludarabine Phosphate Injection. These include advanced age, renal impairment, and bone marrow impairment. Such patients should be monitored closely for excessive toxicity and the dose modified accordingly. The optimal duration of treatment has not been clearly established. It is recommended that three additional cycles of Fludarabine Phosphate Injection be administered following the achievement of a maximal response and then the drug should be discontinued. 2.2 Renal Impairment Adjustments to the starting dose are recommended to provide appropriate drug exposure in patients with creatinine clearance 30 to 79 mL/min, as estimated by the Cockroft-Gault equations.

( see BOXED WARNINGS ) Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia. Monitor blood counts before and during treatment. ( 5.2 ) Transfusion-associated graft-versus-host disease. Use only irradiated blood products for transfusions. ( 5.4 ) Infections. Monitor for infection. ( 5.2 ) Renal Insufficiency. Reduce dose for moderate renal impairment and monitor closely. Do not administer to patients with severe renal impairment. ( 5.9 ) Tumor lysis syndrome (TLS). Take precautions for patients at high risk for TLS. ( 5.8 ) Can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant. ( 5.6 ) 5.1 Dose Dependent Neurologic Toxicities There are clear dose dependent toxic effects seen with fludarabine phosphate. Dose levels approximately 4 times greater (96 mg/m 2 /day for 5 to 7 days) than that recommended for CLL (25 mg/m 2 /day for 5 days) were associated with a syndrome characterized by delayed blindness, coma and death. Symptoms appeared from 21 to 60 days following the last dose. Thirteen of 36 patients (36%) who received fludarabine phosphate at high doses (96 mg/m 2 /day for 5 to 7 days) developed this severe neurotoxicity. 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. In post-marketing experience neurotoxicity has been reported to occur either earlier or later than in clinical trials (range 7 to 225 days).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Very common adverse reactions include myelosuppression (neutropenia, thrombocytopenia and anemia), fever and chills, fatigue, weakness, infection, pneumonia, cough, nausea, vomiting and diarrhea. Other commonly reported events include malaise, mucositis, and anorexia. Serious opportunistic infections have occurred in CLL patients treated with fludarabine phosphate. The most frequently reported adverse reactions and those reactions which are more clearly related to the drug are arranged below according to body system. Most common adverse reactions (incidence > 30%) include myelosuppression (neutropenia, thrombocytopenia and anemia), fever, infection, nausea and vomiting, fatigue, anorexia, cough and weakness ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Areva at 1-855-853-4760 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Hematopoietic Systems Hematologic events (neutropenia, thrombocytopenia, and/or anemia) were reported in the majority of CLL patients treated with fludarabine phosphate. During fludarabine phosphate treatment of 133 patients with CLL, the absolute neutrophil count decreased to less than 500/mm 3 in 59% of patients, hemoglobin decreased from pretreatment values by at least 2 grams percent in 60%, and platelet count decreased from pretreatment values by at least 50% in 55%.

Renal Impairment: Fludarabine Phosphate Injection should not be used in patients with creatinine clearance <30 mL/min/1.73 m 2 . For patients with creatinine clearance 30 to 70 mL/min/1.73 m 2 , reduce the dose ( 2.2 , 5.9 , 8.6 ) See 17 for PATIENT COUNSELING INFORMATION. 8.1 Pregnancy [See Warnings and Precautions ( 5.6 )]. Based on its mechanism of action, fludarabine phosphate can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Fludarabine Phosphate Injection in pregnant women. In rats, repeated intravenous doses of fludarabine phosphate at 2.4 times and 7.2 times the recommended human intravenous dose (25 mg/m 2 ) administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations (cleft palate, exencephaly, and fetal vertebrae deformities) and decreased fetal body weights. Maternal toxicity was not apparent at 2.4 times the human intravenous dose, and was limited to slight body weight decreases at 7.2 times the human intravenous dose. In rabbits, repeated intravenous doses of fludarabine phosphate at 3.8 times the human intravenous dose administered during organogenesis increased embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses.

Metabolism

Phase I studies in humans have demonstrated that fludarabine phosphate is rapidly converted to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous infusion. Consequently, clinical pharmacology studies have focused on 2-fluoro-ara-A pharmacokinetics.

High doses of fludarabine phosphate [see Warnings and Precautions (5)] have been associated with an irreversible central nervous system toxicity characterized by delayed blindness, coma and death. High doses are also associated with severe thrombocytopenia and neutropenia due to bone marrow suppression. There is no known specific antidote for fludarabine phosphate overdosage. Treatment consists of drug discontinuation and supportive therapy.

• Apr 28, 2004ANDAANDA076661Sagent Pharms Inc
• Oct 15, 2007ANDAANDA078393Fresenius Kabi Usa
• Feb 11, 2009ANDAANDA078610Actavis Totowa
• Sep 27, 2010ANDAANDA090724Areva Pharms

1. 1Off Label Use4,19911%
2. 2Pyrexia2,8997.6%
3. 3Drug Ineffective2,8967.6%
4. 4Cytokine Release Syndrome2,8307.4%
5. 5Febrile Neutropenia2,7807.3%
6. 6Product Use In Unapproved Indication2,2395.8%
7. 7Neutropenia1,9745.2%
8. 8Cytomegalovirus Infection1,6554.3%
9. 9Thrombocytopenia1,5754.1%
10. 10Sepsis1,5063.9%
11. 11Acute Graft Versus Host Disease1,5043.9%
12. 12Pneumonia1,4263.7%
13. 13Mucosal Inflammation1,3703.6%
14. 14Infection1,3633.6%
15. 15Pancytopenia1,3443.5%

The 10 most recently updated of 2,595 ClinicalTrials.gov registrations naming Fludarabine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies
  Recruiting · Phase 1 · Phase 2 · Interventional · 44 enrolled · M.D. Anderson Cancer Center
  NCT06383572updated 2026-06-12
• CD30 CAR for CD30+ NSGCT
  Completed · Phase 2 · Interventional · 2 enrolled · UNC Lineberger Comprehensive Cancer Center
  NCT05634785updated 2026-06-12
• CD22 CAR T-cells to Extend Remission Following Commercial CD19 CAR T-cells in Children, Adolescents, and Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
  Recruiting · Phase 2 · Interventional · 20 enrolled · National Cancer Institute (NCI)
  NCT07328503updated 2026-06-12
• Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
  Not yet recruiting · Phase 1 · Interventional · 40 enrolled · National Cancer Institute (NCI)
  NCT07509034updated 2026-06-12
• E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
  Recruiting · Phase 2 · Interventional · 20 enrolled · Christian Hinrichs
  NCT05686226updated 2026-06-12
• Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers
  Not yet recruiting · Phase 2 · Interventional · 98 enrolled · National Cancer Institute (NCI)
  NCT07524530updated 2026-06-12
• A Study of Fludarabine Dosing in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia
  Recruiting · Phase 3 · Interventional · 130 enrolled · Memorial Sloan Kettering Cancer Center
  NCT07223021updated 2026-06-12
• Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL
  Active not recruiting · Phase 1 · Interventional · 43 enrolled · UNC Lineberger Comprehensive Cancer Center
  NCT03602157updated 2026-06-12
• Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
  Not yet recruiting · Phase 1 · Interventional · 57 enrolled · National Cancer Institute (NCI)
  NCT07572136updated 2026-06-12
• KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer
  Recruiting · Phase 1 · Interventional · 30 enrolled · Christian Hinrichs
  NCT05483491updated 2026-06-12

Frequently asked questions

How does Fludarabine work?

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.

What is Fludarabine used for?

According to FDA labeling, Fludarabine carries indications including: Fludarabine Phosphate Injection is a nucleotide metabolic inhibitor indicated for: The treatment of adult 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. Benefit in treatment-naïve or non-refractory CLL patients is not established.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Fludarabine?

Fludarabine is classified as Purine analogues, Nucleoside Metabolic Inhibitor, Nucleic Acid Synthesis Inhibitors, Decreased DNA Integrity.

What are the contraindications for Fludarabine?

Fludarabine labeling lists contraindications including: None None. Always consult the full prescribing information and a clinician.