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.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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