Fludarabin Phosphate

Indications

Fludarabin Phosphate is used for: Chronic lymphocytic leukaemia

Adult Dose

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

Child Dose

Safety and efficacy not established

Renal Dose

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

Administration

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

Contra Indications

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

Precautions

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

Pregnancy-Lactation

Interactions

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.

Adverse Effects

Side effects of Fludarabin Phosphate : >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.

Mechanism of Action

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.