Overview
11 DESCRIPTION Fludarabine Phosphate Injection contains fludarabine phosphate, a nucleotide metabolic inhibitor. Fludarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9- ß -D-arabinofuranosyladenine (ara-A), that is relatively resistant to deamination by adenosine deaminase.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.3 Pharmacokinetics 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.
Indications
- 1 INDICATIONS AND USAGE 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. ( 1.1 ) 1.1 Indication Fludarabine Phosphate Injection is indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease...
Common Doses
- 25 mg
- 70 mL
- 79 mL
- 30 mL
Dosage
2 DOSAGE AND ADMINISTRATION 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.
Black Box Warning
WARNING: SEVERE BONE MARROW SUPPRESSION, CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY Fludarabine Phosphate Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Fludarabine phosphate injection can severely suppress bone marrow function. When used at high doses in dose-ranging studies in patients with acute leukemia, fludarabine phosphate was associated with severe neurologic effects, including blindness, coma, and death.
Contraindications
- 4 CONTRAINDICATIONS None None
Side Effects
- 6 ADVERSE REACTIONS 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.
Interactions
- 7 DRUG INTERACTIONS Fludarabine phosphate injection in combination with pentostatin is not recommended due to the risk of severe pulmonary toxicity ( 5.5 and 7.1 ). 7.1 Pentostatin The use of Fludarabine Phosphate Injection in combination with pentostatin is not recommended due to the risk of fatal pulmonary toxicity [see Warnings and Precautions ( 5.5 )].