Fludarabine phosphate

CLINICAL USE

B-cell chronic lymphocytic leukaemia

DOSE IN NORMAL RENAL FUNCTION

IV: 25 mg/m2 daily for 5 days, repeated every 28 daysOral: 40 mg/m2 for 5 days every 28 days

PHARMACOKINETICS

Molecular weight :365.2

%Protein binding :19–29

%Excreted unchanged in urine : 40–60

Volume of distribution (L/kg) :0.8–4

half-life – normal/ESRD (hrs) :20/24

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

30–70 50–75% of normal dose10–30 50–75% of normal dose. Use with care

<10 : 50% of normal dose. Use with care

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unknown dialysability. Dose as in GFR <10 mL/min

HD :Unknown dialysability. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in GFR=10–30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosisCytotoxics: increased pulmonary toxicity with pentostatin (unacceptably high incidence of fatalities); increases intracellular concentration of cytarabine

ADMINISTRATION

Reconstition

Reconstitute each vial with 2 mL of water to give a concentration of 25 mg/mL

Route

IV, oral

Rate of Administration

Infusion should be administered over 30 minutes

Comments

IV bolus in 10 mL of sodium chloride 0.9%

IV infusion

in 100 mL of sodium chloride 0.9%

OTHER INFORMATION

Rapidly dephosphorylated in plasma to (2-F-9-ß-D-arabinofuranosyladenine) 2-F-ara-ATP, which is necessary for cellular uptakeApproximately 60% of an administered dose is excreted in the urine within 24 hrsAdminister up to achievement of clinical response (usually 6 cycles) then discontinuePatients with renal failure (GFR=17– 41 mL/min/m2) receiving 20% of dose had a similar AUC as patients with normal renal function receiving the full doseFludarabine phosphate.

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