Dacarbazine.JPG

Dacarbazine

CLINICAL USE

Antineoplastic agent:Metastatic melanoma Hodgkin’s disease Soft tissue sarcomas

DOSE IN NORMAL RENAL FUNCTION

Single agent: 2–4.5 mg/kg daily for 10 days, repeated every 4 weeks or 200–250 mg/m2 daily for 5 days, repeated every 3 weeks or 850 mg/m2 on day 1 then once every 3 weeksHodgkin’s disease: 150 mg/m 2 daily for 5 days, repeated every 4 weeks (or 375 mg/m2 every 15 days in combination)

PHARMACOKINETICS

  • Molecular weight                           :182.2
  • %Protein binding                           :0–5
  • %Excreted unchanged in urine     :
  • 20 to 50     :
  • Volume of distribution (L/kg)       :1.49
  • half-life – normal/ESRD (hrs)      :0.5–5/Increased

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    45–60 80% of dose30–45 75% of dose<30 70% of dose, use with caution

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Likely dialysability. Dose as in GFR<30 mL/min
  • HD                     :Likely dialysability. Dose as in GFR<30 mL/min
  • HDF/high flux   :Likely dialysability. Dose as in GFR<30 mL/min
  • CAV/VVHD      :Likely dialysability. Dose as in GFR<30 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsNone known

    ADMINISTRATION

    Reconstition

    10 mL water for injection per 100 mg vial (50 mL for 1 g vial)

    Route

    IV

    Rate of Administration

    Bolus: 1–2 minutes Infusion: 15–30 minutes

    Comments

    For infusion can be diluted with up to 125–300 mL glucose 5% or sodium chloride 0.9%Avoid contact with skin and mucous membranesProtect from light Doses above 200 mg/m 2 should be given as infusions

    OTHER INFORMATION

    Nadir for white cell count usually occurs 21–25 days after a doseDacarbazine (DTIC) is assumed to be inactive. Microsomal metabolism in the liver produces main metabolite; 5-aminoimidazole-4-carboxamide (AIC). Approximately 50% DTIC is renally cleared. Half of this is unchanged DTIC and approximately 50% is AIC. DTIC is secreted via the renal tubules, rather than filtered at the glomerulus Doses from Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function.