FLUDARA
Clinical safety rating
cautionComprehensive clinical and safety monograph for FLUDARA (FLUDARA).
Comprehensive clinical and safety monograph for FLUDARA (FLUDARA).
B-cell chronic lymphocytic leukemia (CLL) in adults who have not responded to or have progressed during treatment with at least one standard alkylating-agent regimenOff-label: non-Hodgkin lymphoma, acute myeloid leukemia, conditioning for hematopoietic stem cell transplantation
Increased risk of infection, Vomiting, Weakness, Nausea, Fatigue, Fever, Decreased blood cells (red cells, white cells, and platelets), Diarrhea, Cough
Fludarabine is a purine nucleotide analog that inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase, leading to cell death in dividing lymphocytes.
| Metabolism | Fludarabine is dephosphorylated in serum to 9-β-D-arabinofuranosyl-2-fluoroadenine (F-ara-A), which is then phosphorylated intracellularly to active triphosphate (F-ara-ATP). Further metabolism involves deamination by adenosine deaminase, but the primary route is renal excretion of unchanged drug and metabolites. |
| Excretion | Renal: 60% excreted unchanged in urine; biliary/fecal: <5% as metabolites. |
| Half-life | Fludarabine phosphate: 0.7-1 h (rapid dephosphorylation). Active metabolite 2-fluoro-ara-A: terminal t1/2 20-30 h (up to 40 h in renal impairment). |
| Protein binding | Fludarabine: 19-29% (primarily albumin); 2-fluoro-ara-A: minimal binding. |
| Volume of Distribution | Vd: 2.4 L/kg (fludarabine); 0.5-0.9 L/kg (2-fluoro-ara-A, approximating total body water). |
| Bioavailability | Oral: 55-75% under fasting conditions; food reduces Cmax but not AUC. |
| Onset of Action | IV: Onset 2-3 days for reduction in lymphocyte count; maximal effect after 1-2 cycles. |
| Duration of Action | Duration of immunosuppression: 6-12 months after therapy; myelosuppression may persist ≥4 weeks. |
| Molecular Weight | 285.23 |
| Action Class | Antimetabolites |
| Brand Substitutes | Fludaphos 50mg Injection, Fludarither 50 Injection, Fludacel 50mg Injection, Naprobin 50mg Injection, Fludocyte 50mg Injection, Lymfuda 10mg Tablet, Fludabine 10mg Tablet |
25 mg/m^2 intravenously over 30 minutes daily for 5 consecutive days every 28 days.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 30-70 mL/min: reduce dose by 20%. CrCl <30 mL/min: contraindicated. |
| Liver impairment | No specific recommendations for hepatic impairment; use with caution in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not established for pediatric patients; safety and efficacy not determined. |
| Geriatric use | No specific adjustment; monitor renal function and hematologic parameters closely. |
| 1st trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
| 2nd trimester | Contraindicated due to risk of fetal harm. |
| 3rd trimester | Contraindicated due to risk of neonatal myelosuppression. |
Clinical note
Comprehensive clinical and safety monograph for FLUDARA (FLUDARA).
| Placental transfer | Crosses placenta; documented in human studies. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants; discontinue breastfeeding or drug. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Fludarabine is contraindicated in pregnancy. It is a nucleoside analog with known teratogenic and embryotoxic effects. First trimester exposure is associated with major congenital malformations, particularly neural tube defects, craniofacial anomalies, and limb defects. Second and third trimester exposure can cause fetal growth restriction, myelosuppression, and increased risk of fetal death. Both animal studies and human case reports confirm significant fetal harm. |
| Fetal Monitoring | If inadvertent exposure during pregnancy occurs, serial fetal ultrasounds for structural anomalies, growth parameters, and amniotic fluid volume are recommended. Maternal complete blood counts with differential and platelet count should be monitored weekly due to risk of myelosuppression. Assess for signs of infection or bleeding. Fetal heart rate monitoring may be considered after 24 weeks gestation. |
| Fertility Effects | Fludarabine can cause irreversible gonadal suppression in both sexes. In males, it may lead to azoospermia or oligospermia; in females, ovarian failure and premature menopause have been reported. Fertility preservation options (e.g., sperm or oocyte cryopreservation) should be discussed prior to initiation. Long-term data suggest a dose-dependent effect on reproductive function. |
■ FDA Black Box Warning
WARNING: FLUDARA MAY CAUSE SEVERE BONE MARROW SUPPRESSION (ANEMIA, THROMBOCYTOPENIA, NEUTROPENIA) AND MAY INDUCE AUTOIMMUNE HEMOLYTIC ANEMIA. PATIENTS SHOULD BE MONITORED CLOSELY FOR HEMATOLOGIC TOXICITY. NEUROTOXICITY (INCLUDING BLINDNESS, COMA, AND DEATH) HAS BEEN REPORTED, PARTICULARLY AT HIGH DOSES (>40 mg/m2/day).
| Serious Effects |
Hypersensitivity to fludarabine or any componentSevere bone marrow suppressionPregnancyBreastfeedingConcurrent use with pentostatin
| Precautions | Severe bone marrow suppression, particularly thrombocytopenia, anemia, and neutropenia, Autoimmune hemolytic anemia, which can be fatal, Neurotoxicity, especially at high doses; monitor for altered mental status, visual disturbances, seizures, Tumor lysis syndrome, especially in patients with high tumor burden, Immunosuppression and increased risk of opportunistic infections, Pulmonary toxicity including interstitial pneumonitis, Hepatotoxicity and increased liver enzymes, Use with caution in renal impairment; dose adjustment required (CrCl <30 mL/min) |
| Food/Dietary | No specific dietary restrictions. Maintain adequate hydration. Grapefruit juice may interact; avoid excessive consumption. Avoid alcohol due to possible hepatotoxicity. |
| Clinical Pearls | Fludarabine is a purine analog used in B-cell chronic lymphocytic leukemia (CLL). It requires dose adjustment in renal impairment (CrCl <30 mL/min). Myelosuppression is dose-limiting; monitor blood counts. Use with caution in patients with prior autoimmune hemolytic anemia. Trimethoprim-sulfamethoxazole should be given for Pneumocystis jirovecii prophylaxis. Allopurinol is recommended for tumor lysis syndrome prevention. Administer IV over 30 minutes or longer. |
| Patient Advice | Take this medication exactly as prescribed by your doctor. · You will need regular blood tests to monitor your blood cell counts. · Avoid live vaccines during treatment and for 12 months after. · Report any signs of infection (fever, chills, sore throat) or unusual bleeding/bruising immediately. · Use effective contraception during treatment and for at least 6 months after the last dose. · Drink plenty of fluids to help prevent kidney problems. · Avoid exposure to people with infections. |
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