DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAntipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis

ADMINISTRATION

Reconstition

–

Route

IV infusion

, IV injection, SC, intrathecal

Rate of Administration

IV injection: rapid

IV infusion

: 1–24 hours

Comments

Patients generally tolerate higher doses when medication given by rapid IV injection (compared with slow infusion), due to the rapid metabolism of cytarabine and the consequent short duration of action of the high dose

OTHER INFORMATION

Cytarabine is concentrated in the liver. A major fraction of dose is inactivated by cytidine deaminase in the liver and other body tissues. After 24 hrs, 80% of dose has been eliminated either as the inactive metabolite or as unchanged cytarabine, mostly in the urine, but some in the bileElevated baseline serum creatinine (>1.2 mg/dl) is an independent risk factor for the development of neurotoxicity during treatment with high-dose cytarabine. Retrospective analysis implicates impaired renal function as an independent risk factor for high-dose cytarabine-induced cerebral and cerebellar toxicity. The incidence of neurotoxicity was 86–100% following administration of high-dose cytarabine to patients with CrCl <40 mL/min and 60–76% following administration to patients with CrCl <60 mL/min. In contrast, when patients with CrCl >60 mL/min received high-dose cytarabine, the incidence of neurotoxicity was found to be 8%, which correlates with the overall incidence of this adverse effect. Accordingly, it has been suggested that high-dose cytarabine should be used with .198 CYtARAbINecaution in patients with impaired renal function: GFR (mL/min) Dose45–60 60%30–45 50%<30 AvoidAnecdotally, an initial dose of 25% of the normal dose has been given to patients with a GFR<20 mL/min, with subsequent doses escalated according to tolerance.