Dosage guidance:
Safety: Consider hydration and prophylactic antihyperuricemic therapy in patients at risk for tumor lysis syndrome. Patients who are receiving or have received fludarabine and require a blood transfusion should receive irradiated blood only to minimize the risk of transfusion-associated graft-versus-host disease.
Clinical considerations: Prophylactic anti-infectives should be considered for patients with an increased risk for developing opportunistic infections. Refer to the protocol or institutional guidance for additional details of off-label dosing.
Acute myeloid leukemia, newly diagnosed (off-label use): IV: 30 mg/m2/day for 5 days (in combination with cytarabine ± G-CSF ± idarubicin (FA, FLAG, or FLAG-IDA regimens), followed by consolidation therapy (Ref).
C ore binding factor acute myeloid leukemia:
Patients ≤60 years of age: IV: 30 mg/m2/day for 5 days (in combination with filgrastim, cytarabine, and gemtuzumab ozogamicin), followed by postremission therapy of 30 mg/m2/day for 3 days (in combination with filgrastim, cytarabine, and gemtuzumab ozogamicin) for 6 postremission cycles (Ref).
Patients >60 years of age: IV: 30 mg/m2/day for 4 days (in combination with filgrastim, cytarabine, and gemtuzumab ozogamicin), followed by postremission therapy of 30 mg/m2/day for 3 days (in combination with filgrastim, cytarabine, and gemtuzumab ozogamicin) for 6 postremission cycles (Ref).
Acute myeloid leukemia, refractory or high/poor-risk patients (off-label use): IV: 30 mg/m2/day for 5 days (in combination with cytarabine and filgrastim [FLAG regimen]), may repeat once for partial remission (Ref) or 30 mg/m2/day for 5 days for 1 or 2 cycles (in combination with cytarabine, idarubicin, and filgrastim [FLAG-IDA regimen]) (Ref).
Chronic lymphocytic leukemia:
FCR regimen: IV: 25 mg/m2/day for 3 days (days 1 to 3) every 28 days (in combination with cyclophosphamide and rituximab); continue for a total of 6 cycles or until disease progression or unacceptable toxicity (Ref).
Single-agent fludarabine:
IV: 25 mg/m2/day for 5 consecutive days (days 1 to 5) every 28 days (Ref).
Oral (Canadian product; not available in US): Relapsed/refractory disease: Oral: 40 mg/m2 once daily for 5 consecutive days every 28 days.
OFAR regimen (for Richter transformation) (off-label combination): IV: 30 mg/m2/day for 2 days (on days 2 and 3) every 28 days for 6 cycles (in combination with oxaliplatin, cytarabine, and rituximab) (Ref).
Hematopoietic cell transplant, allogeneic, myeloablative conditioning regimen (off-label use): IV: 40 mg/m2/day for 4 days (in combination with busulfan) beginning 6 days prior to transplantation (Ref).
Hematopoietic cell transplant, allogeneic, nonmyeloablative conditioning regimen (off-label use): IV: 30 mg/m2/day for 3 doses beginning 5 days prior to transplant (in combination with cyclophosphamide and rituximab) (Ref) or 30 mg/m2/day for 3 doses beginning 4 or 7 days prior to transplant (in combination with total body irradiation) (Ref).
Hematopoietic cell transplant, allogeneic, reduced-intensity conditioning regimen (off-label use): IV: 30 mg/m2/day for 5 days (in combination with melphalan and alemtuzumab) prior to transplant (Ref) or 30 mg/m2/day for 6 days beginning 10 days prior to transplant or 30 mg/m2/day for 5 days beginning 6 days prior to transplant (in combination with busulfan with or without antithymocyte globulin) (Ref) or 30 mg/m2/day for 2 days beginning 4 days prior to transplant (in combination with cyclophosphamide and thiotepa) (Ref) or 25 mg/m2/day for 5 days (in combination with melphalan) prior to transplant (Ref).
Lymphodepleting therapy prior to autologous T-cell immunotherapy (off-label use):
Prior to afamitresgene autoleucel: IV: 30 mg/m2/day for 4 days (in combination with cyclophosphamide) beginning 7 days (on days −7, −6, −5, and −4) prior to afamitresgene autoleucel infusion on day 0 (Ref).
Prior to axicabtagene ciloleucel: IV: 30 mg/m2/day for 3 days (in combination with cyclophosphamide) beginning 5 days (on days −5, −4, and −3) prior to chimeric antigen receptor (CAR) T-cell infusion on day 0 (Ref).
Prior to brexucabtagene autoleucel: IV: 30 mg/m2/day for 3 days (in combination with cyclophosphamide; for relapsed/refractory mantle cell lymphoma) beginning 5 days (on days −5, −4, and −3) prior to CAR T-cell infusion on day 0 (Ref) or 25 mg/m2/day for 3 days beginning 4 days (on days −4, −3, and −2) prior to CAR T-cell infusion on day 0 (in combination with cyclophosphamide; for relapsed/refractory B-cell precursor acute lymphoblastic leukemia) (Ref).
Prior to ciltacabtagene autoleucel: IV: 30 mg/m2/day for 3 days (in combination with cyclophosphamide) followed 2 to 4 days later by CAR T-cell infusion (Ref).
Prior to idecabtagene vicleucel: IV: 30 mg/m2/day for 3 days (in combination with cyclophosphamide) beginning 5 days (on days −5, −4, and −3) prior to CAR T-cell infusion on day 0 (Ref).
Prior to lifileucel: IV: 25 mg/m2 once daily for 5 days (in combination with cyclophosphamide) beginning 5 days (on days −5 through −1) prior to lifileucel infusion on day 0, followed by in vivo expansion with aldesleukin (Ref).
Prior to lisocabtagene maraleucel: IV: 30 mg/m2/day for 3 days (in combination with cyclophosphamide) followed 2 to 7 days later by CAR T-cell infusion (Ref).
Prior to obecabtagene autoleucel: IV: 30 mg/m2/day for 4 days (in combination with cyclophosphamide) beginning 7 days (on days −6, −5, −4, and −3) prior to the first dose of obecabtagene autoleucel (on day 1) of the treatment schedule; the lymphodepleting regimen should be completed 3 days (±1 day) prior to the first obecabtagene autoleucel infusion, allowing a minimum 48-hour washout (Ref).
Prior to tisagenlecleucel : IV: 25 mg/m2/day for 3 days (in combination with cyclophosphamide; for relapsed/refractory diffuse large B-cell lymphoma) followed 2 to 11 days later by CAR T-cell infusion (Ref) or 30 mg/m2/day for 4 days (in combination with cyclophosphamide; for relapsed/refractory B-cell acute lymphoblastic leukemia) followed 2 to 14 days later by CAR T-cell infusion (Ref).
T-cell large granular lymphocytic leukemia, relapsed/refractory (off-label use): IV: 25 mg/m2/day for 3 days every 28 days for 4 to 6 cycles (Ref).
T-cell prolymphocytic leukemia (off-label use): FMC-A regimen: IV: 25 mg/m2 on days 1, 2, and 3 every 28 days (in combination with mitoxantrone and cyclophosphamide [FMC]) for 2 to 4 cycles; if response demonstrated after initial 2 FMC cycles, then an additional 2 cycles of FMC were administered, followed by alemtuzumab consolidation; if stable disease or progression observed after initial 2 FMC cycles, then proceeded directly to alemtuzumab (Ref).
Waldenström macroglobulinemia, relapsed or refractory (off-label use):
Fludarabine monotherapy: IV: 25 mg/m2/day for 5 days every 28 days; continue for 2 cycles beyond achieving complete or maximum response, up to a maximum of 8 cycles (Ref) or 30 mg/m2/day for 5 days every 28 days for at least 4 cycles; patients with a response received 4 additional cycles or 2 cycles beyond the maximum response level (whichever occurred earlier) (Ref).
FR regimen: IV: 25 mg/m2 once daily for 5 days during weeks 5, 9, 13, 19, 23, and 27 (in combination with rituximab) (Ref).
FCR regimen: IV: 25 mg/m2/day on days 2 to 4 of a 28-day treatment cycle (in combination with cyclophosphamide and rituximab) for up to 6 cycles (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV, Oral:
General dosing recommendations (for nontransplant indications only): Note: General recommendations may differ from those published for certain indications (see "Indication-Specific Recommendations" below). Also, refer to institutional indication-specific protocols, as numerous dosing schedules/adjustments exist depending on disease, response, and concomitant therapies.
CrCl ≥80 mL/minute: No dosage adjustment necessary (Ref).
CrCl 50 to 79 mL/minute: Administer 80% of the usual indication-specific dose (Ref).
CrCl 30 to 49 mL/minute: Administer 60% of the usual indication-specific dose (Ref).
CrCl <30 mL/minute: Use is not recommended (Ref).
Indication-specific recommendations:
Acute myeloid leukemia:
Note: When combined with cytarabine for pharmacologic synergy: Higher systemic fludarabine concentrations, may yield higher intracellular concentrations of triphosphorylated fludarabine and cytarabine (Ref). The synergistic effects of the cytarabine/fludarabine combination may also increase the risk of treatment-related neurotoxicity (Ref). A small trial suggests that lower dose fludarabine (eg, 15 mg/m2, as opposed to the standard 30 mg/m2 dose) may be adequate to produce sufficient intracellular levels of 2-fluoro-ara-ATP to maximize ara-CTP accumulation in patients who may not tolerate higher doses (eg, patients with kidney impairment) (Ref).
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).
eGFR 30 to <60 mL/minute/1.73 m2: Consider alternative protocols. If necessary, consider administering 50% of the usual regimen-specific dose (Ref).
eGFR <30 mL/minute/1.73 m2: Use is not recommended (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (% unknown) (Ref):
IV, Oral: Very limited data; in general, alternative regimens should be considered. Single case reports have described various protocols for administration of reduced-dose fludarabine followed by hemodialysis to limit toxicity (Ref).
Peritoneal dialysis: IV, Oral: No data available. Consider alternative regimens (Ref).
CRRT: IV, Oral: No data available. Consider alternative regimens (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV, Oral: No data available. Consider alternative regimens (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment for hepatic impairment is not likely necessary (Ref).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 (Note: Excludes hematopoietic cell transplantation and CAR T-cell lymphodepletion dosing): Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or renal impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
American Society for Blood and Marrow Transplantation practice guideline committee position statement on conditioning chemotherapy dosing in obesity: Utilize actual body weight for calculation of BSA in fludarabine dosing for hematopoietic cell transplant conditioning regimens in adults (Ref).
Hematologic toxicity: Consider dose delays, dose reductions, or permanent fludarabine discontinuation if recovery has not occurred by the first day of the next scheduled cycle.
Autoimmune cytopenias: Manage as clinically indicated.
Neurotoxicity: Consider fludarabine treatment delay or discontinuation.
Refer to adult dosing. Monitor closely for excess toxicity; may require reduced doses.
(For additional information see "Fludarabine: Pediatric drug information")
Dosage guidance:
Clinical considerations: Refer to individual protocols; details concerning dosing in combination regimens should also be consulted.
Acute lymphocytic leukemia, relapsed/refractory: Limited data available; multiple regimens reported; refer to specific protocol:
FLAG ± IDA regimen: Children and Adolescents: IV: 30 mg/m2/dose; maximum dose: 50 mg/dose; once daily for 5 doses on days 2 to 6 or days 1 to 5 (depending on which cycle, refer to protocol) in combination with cytarabine and filgrastim with or without idarubicin (Ref).
Acute myeloid leukemia (AML), relapsed/refractory: Limited data available; multiple regimens reported; refer to specific protocols:
FLAG ± IDA regimen: Children and Adolescents: IV: 30 mg/m2/dose; maximum dose: 50 mg/dose; once daily for 5 doses on days 2 to 6 or days 1 to 5 (depending on which cycle, refer to protocol) in combination with cytarabine and filgrastim with or without idarubicin (Ref).
FLA + GO regimen: Children and Adolescents: IV: 30 mg/m2/dose once daily for 5 doses on days 1 to 5 in combination with cytarabine, gemtuzumab ozogamicin, and with or without an anthracycline (Ref).
Lymphodepleting therapy prior to chimeric antigen receptor T-cell immunotherapy:
Prior to tisagenlecleucel: Children and Adolescents: IV: 30 mg/m2/dose once daily for 4 days in combination with cyclophosphamide (Ref).
Stem cell transplant, allogeneic, conditioning regimen, reduced intensity: Limited data available; multiple regimens based on indication for transplant:
Malignant hematologic disease: Children and Adolescents: IV: 30 mg/m2/dose once daily for 6 doses beginning 7 to 10 days prior to transplant in combination with busulfan and thymoglobulin (Ref).
Non-malignant diseases:
Bone marrow failure syndromes: Children and Adolescents: IV: 30 mg/m2/dose once daily for 5 doses on days −9 to −5 in combination with thiotepa and melphalan with rabbit anti-thymocyte globulin or alemtuzumab (Ref).
Hemophagocytic lymphohistiocytosis: Infants ≥3 months, Children, and Adolescents: IV: 30 mg/m2/dose once daily for 5 doses on days −8 to −4 in combination with busulfan and cyclophosphamide and rabbit anti-thymocyte globulin (Ref).
Severe aplastic anemia: Infants ≥10 months, Children, and Adolescents: IV: 35 mg/m2/dose once daily for 5 doses on days −6 to −2 in combination with cyclophosphamide and rabbit anti-thymocyte globulin (Ref).
Stem cell transplant, allogeneic, conditioning regimen, reduced toxicity: Limited data available:
Malignant hematologic and non-malignant diseases: Children and Adolescents: IV: 30 mg/m2/dose once daily for 6 doses on days −8 to −3 in combination with busulfan and alemtuzumab (Ref).
Stem cell transplant, allogeneic, conditioning regimen, myeloablative: Limited data available:
Malignant hematologic diseases: Children and Adolescents: IV: 30 to 40 mg/m2/dose once daily for 4 to 5 doses in combination with busulfan with or without melphalan and rabbit anti-thymocyte globulin (Ref).
Non-malignant diseases:
Infants >6 months, Children, and Adolescents:
Weight <10 kg: IV: 1.3 mg/kg/dose once daily for 4 doses on days −6 to −3 in combination with busulfan, thiotepa, and rabbit anti-thymocyte globulin (Ref). Note: Pharmacokinetic modeling suggests weight-based dosing does not achieve adequate exposure and patients should receive the body surface area dose (mg/m2) (Ref).
Weight ≥10 kg: IV: 40 mg/m2/dose once daily for 4 doses on days −6 to −3 in combination with busulfan, thiotepa, and rabbit anti-thymocyte globulin (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Specific recommendations for pediatric patients are limited; refer to specific protocol for management in pediatric patients if available, particularly for myelosuppression, hemolysis, and neurotoxicity.
Infants, Children, and Adolescents: The following guidelines have been used by some clinicians (Ref): IV:
GFR >50 mL/minute/1.73 m2: IV: No adjustment required.
GFR 30 to 50 mL/minute/1.73 m2: IV: Administer 80% of dose.
GFR <30 mL/minute/1.73 m2: IV: Not recommended.
Hemodialysis: IV: Administer 25% of dose.
Continuous ambulatory peritoneal dialysis (CAPD): IV: Not recommended.
Continuous renal replacement therapy (CRRT): IV: Administer 80% of dose.
There are no dosage adjustments provided in the manufacturer's labeling; however, data and experience from adult patients suggest that dosage adjustment for hepatic impairment is not likely necessary (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and may be derived from higher than approved dosing.
>10%:
Dermatologic: Skin rash (15%)
Gastrointestinal: Diarrhea (15%), nausea and vomiting (36%)
Hematologic & oncologic: Bone marrow depression (>30%, including anemia, bone marrow aplasia [trilineage], neutropenia, pancytopenia, thrombocytopenia)
Infection: Infection (33%, including herpes zoster infection [reactivation], opportunistic infection, reactivation of latent Epstein-Barr virus, upper respiratory tract infection [2%])
Nervous system: Chills (11%), neurotoxicity (21%, including agitation, asthenia [9%], blindness, cerebral hemorrhage, coma, confusion, optic neuritis, optic neuropathy, peripheral neuropathy, seizure, visual disturbance [3%], wrist-drop), pain (20%)
Respiratory: Pulmonary toxicity (35%, including acute respiratory distress syndrome, pneumonia [16%], pneumonitis, pulmonary fibrosis, pulmonary hemorrhage, pulmonary hypersensitivity reaction, respiratory distress, respiratory failure)
Miscellaneous: Fever (60%)
1% to 10%:
Cardiovascular: Aneurysm (1%), deep vein thrombosis (1%), edema (8%), phlebitis (1%)
Dermatologic: Diaphoresis (1%), pruritus (1%), seborrhea (1%)
Endocrine & metabolic: Dehydration (1%), hyperglycemia (1%)
Gastrointestinal: Anorexia (7%), constipation (1%), dysphagia (1%), esophagitis (3%), gastrointestinal hemorrhage (3%), stomatitis (2% to 9%)
Genitourinary: Dysuria (4%), hematuria (2%), proteinuria (1%), urinary tract infection (2%)
Hematologic & oncologic: Hemorrhage (1%), tumor lysis syndrome (1%)
Hepatic: Abnormal hepatic function tests (1%, including increased liver enzymes), hepatic failure (1%)
Hypersensitivity: Anaphylaxis (1%)
Nervous system: Cerebellar syndrome (1%), depression (1%), difficulty thinking (1%), fatigue (10%), headache (3%), malaise (8%), paresthesia (4%), sleep disturbance (1%), transient ischemic attacks (1%)
Neuromuscular & skeletal: Arthralgia (1%), myalgia (4%), osteoporosis (2%)
Otic: Hearing loss (2%)
Renal: Altered kidney function test (1%), kidney failure (1%)
Respiratory: Bronchitis (1%), cough (10%), dyspnea (9%), epistaxis (1%), hemoptysis (1%), hypoxia (1%), sinusitis (5%)
<1%: Hematologic & oncologic: Myelofibrosis
Postmarketing:
Cardiovascular: Cardiac arrythmia, heart failure
Dermatologic: Erythema multiforme, malignant neoplasm of skin (new onset or exacerbation), pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Lactic acidosis (Smith 2019)
Gastrointestinal: Increased pancreatic enzymes
Genitourinary: Hemorrhagic cystitis
Hematologic & oncologic: Acquired blood coagulation disorder, acute myelocytic leukemia, autoimmune hemolytic anemia (Tsiara 1997), autoimmune thrombocytopenia (Sen 1999), Evan syndrome (Sen 1999), hemolysis (autoimmune) (Sen 1999), hemophagocytic lymphohistiocytosis (Jayakody Arachchillage 2014), immune thrombocytopenia, myelodysplastic syndrome (Yamazaki 2012)
Immunologic: Epstein-Barr-associated lymphoproliferative disorder
Infection: JC virus infection (reactivation: progressive multifocal leukoencephalopathy) (Vidarsson 2002), mycobacterium infection (including tuberculosis [extrapulmonary abscess]) (Leung 2005), reactivation of HBV (Yağci 2000)
Ophthalmic: Vision loss (Virgo 2019)
Respiratory: Interstitial pneumonitis (Garg 2002), pulmonary neoplasm (nodule) (Garg 2002)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to fludarabine or any component of the formulation; severe renal impairment (CrCl <30 mL/minute); decompensated hemolytic anemia; concurrent use with pentostatin.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Autoimmune effects: Life-threatening and sometimes fatal autoimmune effects (including hemolytic anemia, autoimmune thrombocytopenia/idiopathic thrombocytopenic purpura, Evans syndrome, and acquired hemophilia) may occur with fludarabine, including in patients with or without a history of autoimmune hemolytic anemia or a positive Coombs test. A majority of patients rechallenged with fludarabine developed a recurrence of hemolytic effects, although the mechanism for these hemolytic events has not been established.
• Bone marrow suppression: Fludarabine may cause severe and fatal myelosuppression (including neutropenia, thrombocytopenia, and/or anemia). The median time to granulocyte nadir was 13 days (range: 3 to 25 days) and the median time to platelet nadir was 16 days (range: 2 to 32 days). The duration of the cytopenia in reported cases has ranged from approximately 2 months to ~1 year. Cases of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia have been reported (some have been fatal). First-line combination therapy is associated with prolonged cytopenias, with anemia lasting up to 7 months, neutropenia up to 9 months, and thrombocytopenia up to 10 months; increased age is predictive for prolonged cytopenias (Gill 2010).
• Neurotoxicity: Severe CNS adverse reactions (including coma, seizures, agitation, and confusion) may occur with fludarabine. CNS adverse reactions may occur either early or late after fludarabine initiation (range: 7 to 225 days). CNS adverse reactions are dose dependent and occur at greater incidence and severity with higher doses (eg, doses exceeding the recommended fludarabine dose); do not administer fludarabine at doses exceeding the recommended dose. Fatigue, weakness, visual disturbances, confusion, agitation, and seizures may occur; caution patients about performing tasks which require mental alertness (eg, operating machinery or driving).
• Pulmonary toxicity: In clinical studies, patients experienced fatal pulmonary toxicity when treated for refractory chronic lymphocytic leukemia with fludarabine and pentostatin. Avoid the concomitant use of fludarabine and pentostatin.
• Transfusion-associated graft-versus-host disease: Transfusion-associated graft-versus-host disease (GVHD) has been observed following transfusion of non-irradiated blood in patients treated with fludarabine; fatal outcome has been observed. To minimize the risk of transfusion-associated GVHD, patients who are receiving or have received fludarabine and require a blood transfusion should receive irradiated blood only.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) can occur with fludarabine. TLS has been reported in patients with chronic lymphocytic leukemia with a high tumor burden and can occur as early as the first week of treatment.
Special populations:
• Older adults: In patients who received the fludarabine, cyclophosphamide, and rituximab regimen, the incidence of grade 3 or 4 adverse reactions (particularly neutropenia, neutropenic fever, anemia, thrombocytopenia, pancytopenia, and infections) was higher among those ≥70 years of age, compared to patients <70 years of age.
Other warnings/precautions:
• Live vaccines: Avoid vaccination with live vaccines during and after fludarabine treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as phosphate:
Generic: 50 mg/2 mL (2 mL)
Solution, Intravenous, as phosphate [preservative free]:
Generic: 25 mg/mL (2 mL [DSC]); 50 mg/2 mL (2 mL)
Solution Reconstituted, Intravenous, as phosphate [preservative free]:
Generic: 50 mg (1 ea)
Yes
Solution (reconstituted) (Fludarabine Phosphate Intravenous)
50 mg (per each): $113.40
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as phosphate:
Generic: 25 mg/mL (2 mL)
Solution Reconstituted, Intravenous, as phosphate:
Generic: 50 mg (2 mL)
Tablet, Oral:
Fludara: 10 mg
IV: Infuse over 30 minutes. Continuous infusions and IV bolus over 15 minutes have been used for some off-label protocols (refer to individual studies for infusion rate details).
Oral: Tablet [Canadian product] may be administered with or without food; should be swallowed whole with water; do not chew, break, or crush.
Parenteral: Consult specific protocols; IV infusion rates may vary by pediatric protocol.
Intermittent IV infusion: Infuse over 30 minutes; a longer infusion has been used in some protocols of 60 minutes (Ref); a shorter infusion has been used in some protocols (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Chronic lymphocytic leukemia:
Treatment (as a component of a combination regimen) of B-cell chronic lymphocytic leukemia (CLL) in adults.
Treatment of B-cell CLL in adults who have not responded to or have progressed during treatment with at least one regimen containing an alkylating agent.
Acute myeloid leukemia, newly diagnosed; Acute myeloid leukemia, refractory or high/poor risk; Hematopoietic cell transplant (allogeneic) myeloablative conditioning regimen (older adults); Hematopoietic cell transplant (allogeneic) nonmyeloablative conditioning regimen; Hematopoietic cell transplant (allogeneic) reduced-intensity conditioning regimen; Lymphodepleting therapy prior to autologous T-cell immunotherapy; T-cell large granular lymphocytic leukemia, relapsed/refractory; T-cell prolymphocytic leukemia; Waldenström macroglobulinemia, relapsed or refractory
Fludarabine may be confused with cladribine, clofarabine, cytarabine, floxuridine, flucytosine, Flumadine, nelarabine.
Fludara may be confused with FUDR.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pentostatin: May increase adverse/toxic effects of Fludarabine. Specifically, the risk of fatal pulmonary toxicity may be increased. Risk X: Avoid
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last fludarabine dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last dose of fludarabine.
Fludarabine is associated with a risk of infertility (ESMO [Lambertini 2020]). Fludarabine may damage testicular tissue and spermatozoa and possibly result in sperm DNA damage. Recommendations are available for fertility preservation of patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to fludarabine may cause fetal harm.
Outcome data following maternal use of fludarabine during pregnancy (NTP 2013) or following hematopoietic cell transplant (Jasak 2024; Lazzari 2021; Papageorgiou 2012) are limited.
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary (obstetrician, neonatologist, oncology) team approach. In general, if chemotherapy is indicated, it should be avoided during in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation. Specific use of fludarabine is not discussed (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
It is not known if fludarabine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last fludarabine dose.
CBC with differential (at baseline, prior to and during each treatment cycle, and as clinically indicated). AST, ALT, SCr, serum albumin, uric acid. Verify pregnancy status prior to treatment in patients who could become pregnant. Assess risk for opportunistic infections (eg, pneumocystis jirovecii pneumonia, herpes virus infection). Monitor for signs/symptoms of neurologic toxicity (during and after fludarabine treatment) and autoimmune cytopenias (eg, hemolytic anemia, autoimmune thrombocytopenia/idiopathic thrombocytopenic purpura, Evans syndrome, and acquired hemophilia), hemolysis, infection, progressive multifocal leukoencephalopathy and tumor lysis syndrome. Monitor patients with kidney function impairment closely for excess toxicity.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Fludarabine phosphate is a prodrug that is rapidly converted to 2-fluoro-ara-ATP (active), which inhibits DNA synthesis by inhibition of DNA polymerase, ribonucleotide reductase, and DNA primase.
Distribution: Vss: 11 to 96 L/m2 (Johnson 2000).
Protein binding: 2-fluoro-ara-A: 19% to 29%.
Metabolism: IV: Fludarabine phosphate is rapidly dephosphorylated in the plasma to 2-fluoro-ara-A (active metabolite), which subsequently enters tumor cells and is phosphorylated by deoxycytidine kinase to the active triphosphate derivative (2-fluoro-ara-ATP).
Bioavailability: Oral: 2-fluoro-ara-A: 50% to 65%.
Half-life elimination: 2-fluoro-ara-A: Adults: ~20 hours.
Time to peak, plasma: Oral: 1 to 2 hours.
Excretion: Urine (primarily) (Johnson 2000); clearance via the kidneys represents ~40% of total body clearance.
Altered kidney function: Total body clearance of the principal metabolite (2-fluoro-ara-A) correlates with CrCl. Mean body clearance is 124 mL/minute for patients with moderate renal impairment and 71 mL/minute for patients with severe renal impairment. In 2 patients with a median CrCl of 22 mL/minute/m2, clearance was reduced by 56%.