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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :182.2

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :0–5

%Excreted unchanged in urine &nbsp &nbsp :

20 to 50 &nbsp &nbsp :

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :1.49

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Likely dialysability. Dose as in GFR<30 mL/min

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Likely dialysability. Dose as in GFR<30 mL/min

HDF/high flux &nbsp :Likely dialysability. Dose as in GFR<30 mL/min

CAV/VVHD &nbsp &nbsp &nbsp: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

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.

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