dosage adjustment of Carmustine in renal failure




Carmustine.JPG

Carmustine

CLINICAL USE

Alkylating agent:
  • Myeloma, lymphoma and brain tumours

    DOSE IN NORMAL RENAL FUNCTION

    150–200 mg/m2 as a single dose or 75–100 mg/m2 on 2 consecutive days every 6 weeks Implants: 7.7mg, maximum 8 implants

    PHARMACOKINETICS

  • Molecular weight                           :214.1
  • %Protein binding                           :77
  • %Excreted unchanged in urine     : 60–70
  • Volume of distribution (L/kg)       :3.25
  • half-life – normal/ESRD (hrs)      :22 minutes/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in normal renal function
  • HD                     :Not dialysed. Dose as in normal renal function
  • HDF/high flux   :Unknown dialysability. Dose as in normal renal function
  • CAV/VVHD      :Not dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsNone known

    ADMINISTRATION

    Reconstition

  • 3 mL of the supplied diluent (absolute ethanol) then add 27 mL of sterile water for injection
  • This solution may be further diluted with sodium chloride 0.9% or glucose 5% for injection

    Route

    IV

    Rate of Administration

  • Administer by IV drip over a period of 1–2 hours

    Comments

  • Therapy should not be repeated before 6 weeks
  • Can further dilute the reconstituted solution with 500 mL of sodium chloride 0.9% or glucose 5%

    OTHER INFORMATION

  • Renal abnormalities, e.g. a decrease in kidney size: progressive azotaemia and renal failure have been reported in patients receiving large cumulative doses after prolonged therapy
  • Partially metabolised to active species by liver microsomal enzymes, which have a long T½. It is thought that the antineoplastic activity may be due to metabolites. Approximately 30% of a dose is excreted in the urine after 24 hours, and 60–70% of the total dose after 96 hours. About 10% is excreted as respiratory CO2. Terminal half-life of the metabolites are about 1 hour.