Trade Names:Fludara- Injection, lyophilized cake for solution 50 mg
Trade Names:Fludarabine Phosphate- Injection, solution 25 mg/mL
Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidarabine. Fludarabine's metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thus inhibiting DNA synthesis.
Fludarabine is rapidly converted to the active metabolite, 2î“¸fluoroî“¸araî“¸A, within minutes after IV infusion.
In vitro, plasma protein binding of fludarabine ranged between 19% and 29%.
The terminal half-life of 2î“¸fluoroî“¸araî“¸A is approximately 20 h. Renal Cl represents approximately 40% of the total body Cl.
Total body Cl of the principal metabolite correlates with CrCl. Mean body Cl is 172 mL/min in individuals with healthy renal function compared with 124 mL/min for patients with moderate renal function impairment (ie, 17 to 41 mL/min/m 2 ).
Refractory or progressive B-cell chronic lymphocytic leukemia (CLL).
Leukemias, non-Hodgkin lymphoma.
IV 25 mg/m 2 /day over approximately 30 min daily for 5 consecutive days. Each 5î“¸day course should commence every 28 days.Renal Function ImpairmentAdults
IV Reduce dose 20% in patients with moderate renal function impairment (CrCl 30 to 70 mL/min/1.73 m 2 ). Do not administer in patients with severely impaired renal function (CrCl less than 30 mL/min/1.73 m 2 ).
Store refrigerated between 36° and 46°F.
Pharmacologic effect of digoxin (oral) may be decreased because of decreased GI absorption caused by fludarabine.Pentostatin
Concomitant therapy may cause severe or fatal pulmonary toxicity. Coadministration is not recommended.Vaccination
Avoid vaccination with live vaccines during and after treatment.
None well documented.
Angina (6%); arrhythmia, cerebrovascular accident, CHF, deep vein thrombosis, MI, phlebitis, supraventricular tachycardia (3%); aneurysm, transient ischemic attack.
Weakness (65%); fatigue (38%); paresthesia (12%); malaise (8%); headache, sleep disorder (3%); cerebellar syndrome, depression, impaired mentation (1%); multifocal leukoencephalopathy (postmarketing); agitation; coma; confusion; weakness.
Rash (15%); diaphoresis (13%); alopecia, pruritus (3%); seborrhea (1%); erythema multiforme, new onset of skin cancer, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis, worsening or flare-up of preexisting skin cancer.
Visual disturbances (15%); pharyngitis (9%); hearing loss (6%).
Nausea/vomiting (36%); anorexia (34%); diarrhea (15%); GI bleeding (13%); stomatitis (9%); constipation, esophagitis (3%); mucositis (2%); dysphagia (1%).
Urinary infection (15%); dysuria (4%); hematuria, urinary hesitancy (3%); abnormal renal function tests, proteinuria, renal failure (1%); hemorrhagic cystitis.
Anemia (60%); neutropenia (59%); thrombocytopenia (55%); hemorrhage (1%); acute myeloid leukemia, autoimmune hemolytic anemia, myelodysplastic syndrome, pancytopenia (postmarketing).
Abnormal LFTs, cholelithiasis (3%); liver failure (1%).
Hyperglycemia (6%); dehydration, tumor lysis syndrome (including hematuria, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, metabolic acidosis, renal failure, urate crystalluria) (1%).
Myalgia (16%); osteoporosis (2%); arthralgia (1%).
Cough (44%); dyspnea, pneumonia (22%); upper respiratory tract infection (16%); allergic pneumonitis, hemoptysis (6%); sinusitis (5%); bronchitis, epistaxis, hypoxia (1%); acute respiratory distress syndrome, hemoptysis, pulmonary hypersensitivity; pulmonary fibrosis, pulmonary hemorrhage, respiratory distress, respiratory failure (postmarketing).
Fever (69%); infection (44%); pain (22%); chills, edema (19%).
WarningsBone marrow suppression
Severe depression of bone marrow function can occur. Life-threatening and sometimes fatal autoimmune phenomena, such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura, Evan syndrome, and acquired hemophilia, have occurred after 1 or more cycles of treatment. Closely evaluate and monitor patients for hemolytic anemia.Neurotoxicity
When used in high doses in dose-ranging studies in patients with acute leukemia, severe neurologic effects (including blindness, coma, and death) have occurred. Severe CNS toxicity occurred in 36% of patients treated with doses 4 times more than the recommended dose. Similar CNS toxicity, including coma, seizures, agitation, and confusion, has been reported in patients treated at doses in the recommended dose range for CLL.Pentostatin cotreatment
Coadministration with pentostatin is not recommended because of the high incidence of fatal pulmonary toxicity.
Closely evaluate and monitor patients for hemolytic anemia. Closely monitor patients for signs of hematologic and nonhematologic toxicity. Periodic assessment of peripheral blood cell counts is recommended to detect anemia, neutropenia, and thrombocytopenia.
Category D .
Safety and efficacy not established.
Use with caution in patients with severe impairment of bone marrow function, immunodeficiency, or a history of opportunistic infection.
Disease progression and transformation (eg, Richter syndrome) have been reported in patients with CLL.
There are clear dose-dependent toxic effects seen with fludarabine.
Transfusion-associated graft-versus-host disease may occur after transfusion of nonirradiated blood.
Irreversible CNS toxicity characterized by delayed blindness, coma, and death; severe thrombocytopenia and neutropenia.
Copyright © 2009 Wolters Kluwer Health.