CLINICAL USE

Prophylaxis of urothelial toxicity in patients treated with ifosfamide or cyclophosphamide

DOSE IN NORMAL RENAL FUNCTION

Dose and timing depends on cytotoxic agent and on route of administration of mesna

PHARMACOKINETICS

  • Molecular weight                           :164.2
  • %Protein binding                           :70
  • %Excreted unchanged in urine     : 32
  • Volume of distribution (L/kg)       :0.65
  • half-life – normal/ESRD (hrs)      :0.3/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : See ‘Other Information’
  • 10 to 20     : See ‘Other Information’
  • <10           : See ‘Other Information’

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unknown dialysability. Dose as in GFR <10 mL/min
  • HD                     :Probably dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   :Probably 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 drugs

  • None known

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral, IV bolus,

    IV infusion

    Rate of Administration

    IV bolus: over 15–30 minutes

    IV infusion

    : over 12–24 hours

    Comments

    Compatible with sodium chloride 0.9% and glucose 5%Mesna injection can be administered orally in orange juice or cola to improve palatability

    OTHER INFORMATION

    Urinary output should be maintained at 100 mL/hr (as required for oxazaphosphorine treatment)The dose of mesna is dependent on the dose of oxazaphosphorine, e.g. reduce dose of cyclophosphamide to 50% of normal if GFR

  • <10           : mL/min; hence, dose of mesna will consequently be reducedFrom what is known about the pharmacokinetics and mechanism of action of mesna, its availability in the urinary tract depends on renal functionIn the case of completely anuric patients (extremely rare) neither cyclophosphamide nor its metabolites should appear in the urinary tract: the use of mesna concomitantly may therefore be unnecessary in anuric patients. If there is any risk of cyclophosphamide or its metabolites entering the urinary tract, mesna should probably be given to prevent urothelial toxicityLimited kinetic information would suggest mesna would be eliminated by haemodialysis.
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