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
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
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.