CLINICAL USE

Alkylating antineoplastic agent

DOSE IN NORMAL RENAL FUNCTION

IM, bladder and intracavitary instillations: 60 mg in single or divided doses Intrathecal: maximum 10 mg Other doses depend on indication or local protocol

PHARMACOKINETICS

  • Molecular weight                           : 189.2
  • %Protein binding                           : 10–40
  • %Excreted unchanged in urine     : <2
  • Volume of distribution (L/kg)       : 0.3–1.6
  • half-life – normal/ESRD (hrs)      : 2.4

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : IM: Use a reduced dose with caution
  • 10 to 20     : IM: Use a reduced dose with caution
  • <10           : IM: Use a reduced dose with caution

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                : Unknown dialysability. Dose as in GFR <10 mL/min
  • HD                     : Dialysed. Dose as in GFR
  • <10           : mL/ min
  • HDF/high flux   : Dialysed. Dose as in GFR
  • <10           : mL/ min
  • CAV/VVHD      : Dialysed. Dose as in GFR=10– 20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Antipsychotics: avoid concomitant use with clozapine Avoid concomitant use with other myelosuppressive agents

    ADMINISTRATION

    Reconstition

    1.5 mL water for injection

    Route

    IV, IM, intrathecal (can be administered directly into pleural, pericardial or peritoneal cavities and as a bladder instillation)

    Rate of Administration

    Comments

    OTHER INFORMATION

    Haemorrhagic cystitis has occurred Metabolised in liver to triethylene phosphoramide (TEPA). Only traces of unchanged thiotepa and (TEPA) are excreted in the urine, together with a large proportion of metabolites (60% within 72 hours) .

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