Cytarabine.JPG

Cytarabine

CLINICAL USE

Antineoplastic agent:Acute leukaemias Lymphomatous meningitis

DOSE IN NORMAL RENAL FUNCTION

High-dose (infusional) therapy: 1–3 g/m 2 every 12 hoursLow dose (conventional) therapy: 100 mg/ m2Lymphomatous meningitis: 50 mg (intrathecal) every 14–28 days. See SPC for more information, depends on formulationOr according to local policy

PHARMACOKINETICS

  • Molecular weight                           :243.2
  • %Protein binding                           :13
  • %Excreted unchanged in urine     : 5.8–10
  • Volume of distribution (L/kg)       :2.6
  • half-life – normal/ESRD (hrs)      :1–3 (Intrathecal liposomal: 100–263)/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : 100% of conventional low dose regime. For high dose, see ‘Other Information’
  • 10 to 20     : 100% of conventional low dose regime. For high dose, see ‘Other Information’
  • <10           : 100% of conventional low dose regime. For high dose, see ‘Other Information’

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR <10 mL/min
  • HD                     :Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min
  • CAV/VVHD      :Unknown dialysability. Dose as in GFR 10 to 20 mL/min

    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.