Fludarabine phosphate 50 mg/2mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Nucleoside Metabolic Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Fludarabine injection is used to treat certain types of chronic lymphocytic leukemia (CLL; a type of cancer of the white blood cells). Fludarabine injection is in a class of medications called purine analogs. It works by slowing or stopping the growth of cancer cells in your body.
Read the full MedlinePlus article ↗- Fludarabine Injection is used to treat a type of blood cancer called B-cell chronic lymphocytic leukemia (CLL) — specifically in adults whose disease stopped responding to a previo...
- What exactly is fludarabine being used to treat, and why is it given by IV?
- Common side effects include low blood counts (which raise your risk of infection and bleeding), fever, chills, nausea, fatigue, and skin rash — these are expected and your team wil...
- What side effects should I expect, and which ones should I call my doctor about right away?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
2 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9185 | $206.299 / J9185 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Fludarabine phosphate 50 mg/2mLthis 45963-0609-55 | Actavis | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 45963-0609-55 You're viewing this | 1 VIAL, GLASS in 1 CARTON (45963-609-55) / 2 mL in 1 VIAL, GLASS | 2015-01-05 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: Fludarabine Phosphate for Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Fludarabine Phosphate for Injection can severely suppress bone marrow function. When used at high doses in dose-ranging studies in patients with acute leukemia, Fludarabine Phosphate for Injection 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. 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 for Injection.
Patients undergoing treatment with Fludarabine Phosphate for Injection should be evaluated and closely monitored for hemolysis. In a clinical investigation using Fludarabine Phosphate for Injection 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 for Injection in combination with pentostatin is not recommended.
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Fludarabine Phosphate for Injection is 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. The safety and effectiveness of Fludarabine Phosphate for Injection in previously untreated or non-refractory patients with CLL have not been established.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Usual Dose The recommended adult dose of Fludarabine Phosphate for 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 for 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 for Injection be administered following the achievement of a maximal response and then the drug should be discontinued.
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. These adjustments are based on a pharmacokinetic study in patients with renal impairment. Fludarabine Phosphate for Injection should not be administered to patients with creatinine clearance less than 30 mL/min.
Starting Dose Adjustment for Renal Impairment Creatinine Clearance Starting Dose ≥ 80 mL/min 25 mg/m 2 (full dose) 50 to 79 mL/min 20 mg/m 2 30 to 49 mL/min 15 mg/m 2 < 30 mL/min do not administer Renally impaired patients should be monitored closely for excessive toxicity and the dose modified accordingly. Preparation of Solutions Fludarabine Phosphate for Injection should be prepared for parenteral use by aseptically adding Sterile Water for Injection, USP. When reconstituted with 2 mL of Sterile Water for Injection, the solid cake should fully dissolve in 15 seconds or less; each mL of the resulting solution will contain 25 mg of fludarabine phosphate, 25 mg of mannitol, and sodium hydroxide to adjust the pH to 7.7.
The pH range for the final product is 7.2 to 8.2. In clinical studies, the product has been diluted in 100 cc or 125 cc of 5% Dextrose Injection, USP, or 0.9% Sodium Chloride, USP. Reconstituted Fludarabine Phosphate for Injection contains no antimicrobial preservative and thus should be used within 8 hours of reconstitution.
Care must be taken to assure the sterility of prepared solutions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Fludarabine Phosphate for Injection should not be mixed with other drugs.
Handling and Disposal Procedures for proper handling and disposal should be considered. Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs. Several guidelines on this subject have been published.
1-4. Caution should be exercised in the handling and preparation of Fludarabine Phosphate for Injection solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage.
If the solution contacts the skin or mucous membranes, wash thoroughly with soap and water; rinse eyes thoroughly with plain water. Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.
⛔ Contraindications ▾
CONTRAINDICATIONS Fludarabine Phosphate for Injection is contraindicated in those patients who are hypersensitive to this drug or its components.
⚠️ Warnings ▾
WARNINGS (See BOXED WARNINGS ) Dose Dependent Neurologic Toxicities There are clear dose-dependent toxic effects seen with Fludarabine Phosphate for Injection. 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 for Injection 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).
The effect of chronic administration of Fludarabine Phosphate for Injection on the central nervous system is unknown; however, patients have received the recommended dose for up to 15 courses of therapy. Bone Marrow Suppression Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia, has been reported in patients treated with Fludarabine Phosphate for Injection. In a Phase I study in adult solid tumor patients, the median time to nadir counts was 13 days (range, 3 to 25 days) for granulocytes and 16 days (range, 2 to 32) for platelets.
Most patients had hematologic impairment at baseline either as a result of disease or as a result of prior myelosuppressive therapy. Cumulative myelosuppression may be seen. While chemotherapy-induced myelosuppression is often reversible, administration of Fludarabine Phosphate for Injection requires careful hematologic monitoring.
Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in adult patients. The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year. These episodes have occurred both in previously treated or untreated patients.
Autoimmune Reactions 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 for Injection in patients with or without a previous history of autoimmune hemolytic anemia or a positive Coombs' test and who may or may not be in remission from their disease. Steroids may or may not be effective in controlling these hemolytic episodes.
The majority of patients rechallenged with Fludarabine Phosphate for Injection developed a recurrence in the hemolytic process. The mechanism(s) which predispose patients to the development of this complication has not been identified. Patients undergoing treatment with Fludarabine Phosphate for Injection should be evaluated and closely monitored for hemolysis.
Discontinuation of therapy with Fludarabine Phosphate for Injection is recommended in case of hemolysis. Transfusion Associated Graft-Versus-Host Disease Transfusion-associated graft-versus-host disease has been observed after transfusion of non-irradiated blood in Fludarabine Phosphate for Injection treated patients. Fatal outcome as a consequence of this disease has been reported.
Therefore, to minimize the risk of transfusion-associated graft-versus-host disease, patients who require blood transfusion and who are undergoing, or who have received, treatment with Fludarabine Phosphate for Injection should receive irradiated blood only. Pulmonary Toxicity In a clinical investigation using Fludarabine Phosphate for Injection in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocyt…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS Very common adverse events 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 (such as latent viral reactivation, herpes zoster virus, Epstein-Barr virus, and progressive multifocal leukoencephalopathy) have occurred in CLL patients treated with Fludarabine Phosphate for Injection.
Adverse events and those reactions which are more clearly related to the drug are arranged below according to body system. Hematopoietic Systems Hematologic events (neutropenia, thrombocytopenia, and/or anemia) were reported in the majority of CLL patients treated with Fludarabine Phosphate for Injection. During Fludarabine Phosphate for Injection 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%.
Myelosuppression may be severe, cumulative, and may affect multiple cell lines. Bone marrow fibrosis occurred in one CLL patient treated with Fludarabine Phosphate for Injection. Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in post marketing surveillance.
The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year. These episodes have occurred both in previously treated or untreated patients. 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 in patients receiving Fludarabine Phosphate for Injection (see WARNINGS section).
The majority of patients rechallenged with Fludarabine Phosphate for Injection developed a recurrence in the hemolytic process. In postmarketing experience, cases of myelodysplastic syndrome and acute myeloid leukemia, mainly associated with prior, concomitant or subsequent treatment with alkylating agents, topoisomerase inhibitors, or irradiation have been reported. Infections Serious and sometimes fatal infections, including opportunistic infections and reactivations of latent viral infections such as VZV (herpes zoster), Epstein-Barr virus and JC virus (progressive multifocal leukoencephalopathy) have been reported in patients treated with Fludarabine Phosphate for Injection.
Rare cases of Epstein Barr virus (EBV) associated lymphoproliferative disorders have been reported in patients treated with Fludarabine Phosphate for Injection. In postmarketing experience, cases of progressive multifocal leukoencephalopathy have been reported. Most cases had a fatal outcome.
Many of these cases were confounded by prior and/or concurrent chemotherapy. The time to onset has ranged from a few weeks to approximately one year after initiating treatment. Of the 133 adult CLL patients in the two trials, there were 29 fatalities during study, approximately 50% of which were due to infection.
Metabolic Tumor lysis syndrome has been reported in CLL patients treated with Fludarabine Phosphate for Injection. This complication may include hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, hematuria, urate crystalluria, and renal failure. The onset of this syndrome may be heralded by flank pain and hematuria.
Nervous System (see WARNINGS section) Objective weakness, agitation, confusion, seizures, visual disturbances, optic neuritis, optic neuropathy, blindness and coma have occurred in CLL patients treated with Fludarabine Phosphate for Injection at the recommended dose. Peripheral neuropathy has been observed in patients treated with Fludarabin…
🔄 Drug Interactions ▾
Drug Interactions The use of Fludarabine Phosphate for Injection in combination with pentostatin is not recommended due to the risk of fatal pulmonary toxicity (see WARNINGS section).
🤰 Pregnancy ▾
Pregnancy (See WARNINGS section). Based on its mechanism of action, fludarabine phosphate can cause fetal harm when administered to a pregnant woman. There are not adequate and well-controlled studies of fludarabine phosphate in pregnant women.
Fludarabine phosphate was embryolethal and teratogenic in rats and rabbits. If Fludarabine Phosphate for Injection is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
In rats, repeated intravenous doses of fludarabine phosphate at 2.4 times and 7.2 times the recommended human IV 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 IV dose, and was limited to slight body weight decreases at 7.2 times the human IV dose. In rabbits, repeated intravenous doses of fludarabine phosphate at 3.8 times the human IV dose administered during organogenesis increased embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses.
A significant increase in malformations including cleft palate, hydrocephaly, adactyly, brachydactyly, fusions of the digits, diaphragmatic hernia, heart/great vessel defects, and vertebrae/rib anomalies were seen in all dose levels (≥0.5 times the human IV dose).
🧒 Pediatric Use ▾
Pediatric Use Data submitted to the FDA was insufficient to establish efficacy in any childhood malignancy. Fludarabine Phosphate for Injection was evaluated in 62 pediatric patients (median age 10, range 1 to 21) with refractory acute leukemia (45 patients) or solid tumors (17 patients). The Fludarabine Phosphate for Injection regimen tested for pediatric acute lymphocytic leukemia (ALL) patients was a loading bolus of 10.5 mg/m 2 /day followed by a continuous infusion of 30.5 mg/m 2 /day for 5 days.
In 12 pediatric patients with solid tumors, dose-limiting myelosuppression was observed with a loading dose of 8 mg/m 2 /day followed by a continuous infusion of 23.5 mg/m 2 /day for 5 days. The maximum tolerated dose was a loading dose of 7 mg/m 2 /day followed by a continuous infusion of 20 mg/m 2 /day for 5 days. Treatment toxicity included bone marrow suppression.
Platelet counts appeared to be more sensitive to the effects of Fludarabine Phosphate for Injection than hemoglobin and white blood cell counts. Other adverse events included fever, chills, asthenia, rash, nausea, vomiting, diarrhea, and infection. There were no reported occurrences of peripheral neuropathy or pulmonary hypersensitivity reaction.
🆘 Overdosage ▾
OVERDOSAGE High doses of Fludarabine Phosphate for Injection (see WARNINGS section) 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 for Injection overdosage.
Treatment consists of drug discontinuation and supportive therapy.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY 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.
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. After the five daily doses of 25 mg 2-fluoro-ara-AMP/m 2 to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation.
During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours. In vitro , plasma protein binding of fludarabine ranged between 19% and 29%.
A correlation was noted between the degree of absolute granulocyte count nadir and increased area under the concentration x time curve (AUC). Special Populations Pediatric Patients Limited pharmacokinetic data for Fludarabine Phosphate for Injection are available from a published study of children (ages 1 to 21 years) with refractory acute leukemias or solid tumors (Children's Cancer Group Study 097 1 ). When Fludarabine Phosphate for Injection was administered as a loading dose over 10 minutes immediately followed by a 5-day continuous infusion, steady-state conditions were reached early.
Patients with Renal Impairment The total body clearance of the principal metabolite 2-fluoro-ara-A correlated with the creatinine clearance, indicating the importance of the renal excretion pathway for the elimination of the drug. Renal clearance represents approximately 40% of the total body clearance. Patients with creatinine clearance 30 to 79 mL/min should have their Fludarabine Phosphate for Injection dose reduced and be monitored closely for excessive toxicity.
Due to insufficient data, Fludarabine Phosphate for Injection should not be administered to patients with creatinine clearance less than 30 mL/min (see DOSAGE AND ADMINISTRATION section).
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Fludarabine Phosphate for Injection, USP is a white, lyophilized solid cake. Each single-dose vial contains 50 mg of fludarabine phosphate USP, 50 mg of mannitol, and sodium hydroxide to adjust pH to 7.7. The pH range for the final product is 7.2 to 8.2.
Fludarabine Phosphate for Injection, USP, NDC 45963-609-55, is supplied in a clear glass single-dose vial and packaged in a carton. Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F), in the original package. The container closure is not made with natural rubber latex.
Sterile, Nonpyrogenic, Preservative-free
📋 Description ▾
DESCRIPTION Fludarabine Phosphate for Injection, USP contains fludarabine phosphate USP, a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine (ara-A) that is relatively resistant to deamination by adenosine deaminase. Each vial of sterile lyophilized solid cake contains 50 mg of the active ingredient fludarabine phosphate, 50 mg of mannitol, and sodium hydroxide to adjust pH to 7.7. The pH range for the final product is 7.2 to 8.2.
Reconstitution with 2 mL of Sterile Water for Injection, USP, results in a solution containing 25 mg/mL of fludarabine phosphate intended for intravenous administration. The chemical name for fludarabine phosphate is 9 H -Purin-6-amine, 2-fluoro-9-(5- 0 -phosphono-β-D-arabino-furanosyl) (2-fluoro-ara-AMP). The molecular formula of fludarabine phosphate is C 10 H 13 FN 5 O 7 P (MW 365.2) and the structure is: 9f8c17ab-figure-01