dosage adjustment of Capecitabine in renal failure




Capecitabine.JPG

Capecitabine

CLINICAL USE

Antineoplastic agent (antimetabolite):
  • Colorectal, colon and breast cancer

    DOSE IN NORMAL RENAL FUNCTION

    1.25 g/m2 twice daily for 14 days, repeated after 7 days

    PHARMACOKINETICS

  • Molecular weight                           :359.4
  • %Protein binding                           :54
  • %Excreted unchanged in urine     : 3
  • Volume of distribution (L/kg)       :No data
  • half-life – normal/ESRD (hrs)      :0.85/Increased

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    30–50 75% of dose (950 mg/m2 twice daily) use with care10–30 Avoid
  • <10           : Avoid

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unknown dialysability. Dose as in GFR <10 mL/min
  • HD                     :Unlikely to be dialysed. 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
  • Allopurinol: avoid concomitant use
  • Anticoagulants: possibly enhances effect of coumarins
  • Anti-epileptics: reported toxicity with phenytoin, due to increased phenytoin levels
  • Antipsychotics: avoid concomitant use with clozapine – increased risk of agranulocytosis

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    Give after food

    OTHER INFORMATION

  • Capecitabine is a prodrug that is metabolised to fluorouracil
  • Contraindicated in severe renal impairment due to increased incidence of grade 3 or 4 adverse reactions in patients with GFR of 30–50 mL/min
  • Extensive absorption (~70%) after food intake.
  • First metabolised in the liver and then in the tumour. Up to 96% dose is recovered in the urine. Terminal T½ = 0.85 hours