Fludarabin Phosphate

Chronic lymphocytic leukaemia

B-Cell Chronic Lymphocytic Leukemia 25 mg/sq.meter IV infusion over 30 minutes qD x5 days (up to 30 mg/sq.meter) 40 mg/sq.meter PO x5 days Repeat q28Days

Safety and efficacy not established

Renal impairment CrCl 30-70 mL/min: reduce by 20% CrCl <30 mL/min: IV not recommended; PO reduce 50%

IV Preparation Reconstitute powder for inj with 2 mL SWI to result in a concentration of 25 mg/mL Standard IV dilution: dose/100 mL D5W or NS IV Administration IV infusion over 30 min recommended by Mfr; has been given as continuous infusion or by rapid injection but risk of toxicity may be higher

Renal impairment (CrCl <30 mL/min); decompensated haemolytic anaemia. Pregnancy and lactation. Concomitant use of live vaccines.

Routine monitoring of blood counts and Hb conc. Monitor for signs of autoimmune haemolytic anaemia; elderly. Avoid contact with skin and eyes; avoid inhalation. Myelosuppression may be cumulative and severe increasing risk of opportunistic infections. Increased risk of tumour lysis syndrome in patients with high tumour burden. Lactation: not known if excreted in breast milk, do not nurse

D Pregnancy Category: D Lactation: not known if excreted in breast milk, do not nurse

Co-administration with pentostatin may lead to pulmonary toxicity. Reduced metabolic activation of fludarabine with cytarabine. Reduced therapeutic efficacy with dipyridamole and other adenosine uptake inhibitors.

>10% Fever (69%),Objective weakness (65%),Anemia (60%),Neutropenia (60%),Thrombocytopenia (55%),Leukopenia (partly therapeutic),Infection (44%-not necessarily drug-induced),Cough (44%),Pain (44%),Fatigue (38%),N/V (36%),Anorexia (34%),Malaise (22%),Dyspnea (22%),Pneumonia (9-22%),Edema (19%),Myalgia (16%),URI (16%),UTI (15%),Rash (15%),Diarrhea (15%),Visual disturbances (15%),Diaphoresis (13%),GI bleeding (13%),Paresthesia (12%) 1-10% (selected) Abdominal pain (10%),Back pain (9%),Headache (9%),Pharyngitis (9%),Stomatitis (9%),Flu like syndrome (5-9%),Malaise (6%),Angina (6%),Hearing Loss (2-6%),Peripheral edema (7%),Alopecia (3%),Constipation (1-3%),Arrhythmia (3%),DVT (1%) Potentially Fatal: Myelosuppression. Fatal autoimmune haemolytic anemia.

Fludarabine is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP which inhibits DNA polymerase and ribonucleotide reductase resulting in inhibition of DNA synthesis leading to cell death.