Dacarbazine is available in single-dose vials containing 100 or 200 mg of drug as a powder along with anhydrous citric acid and mannitol.3720 Each 100- or 200-mg vial of dacarbazine should be reconstituted with 9.9 or 19.7 mL, respectively, of sterile water for injection to yield a solution containing 10 mg/mL of dacarbazine.3720
pH
From 3 to 4.3720
Dacarbazine is administered as a direct intravenous injection or as an intravenous infusion after dilution in dextrose 5% or sodium chloride 0.9%.3720 Extravasation may result in severe pain and tissue damage.377; 3720
In the event of spills or leaks, the use of sulfuric acid 10% in contact for 24 hours to inactivate dacarbazine has been recommended.1200
Dacarbazine is a white to pale yellow powder.3720 Intact vials of dacarbazine should be stored under refrigeration at 2 to 8°C and protected from light.3720 However, dacarbazine in intact vials stored at controlled room temperature has been stated to be stable for periods of 4 weeks1239; 1433 to 3 months.1433; 2745 Reconstituted solutions may be stored for up to 8 hours at normal room temperature and light or up to 72 hours at 4°C.3720 However, it has been reported that solutions are stable for at least 24 hours at room temperature (1% decomposition) and at least 96 hours under refrigeration (less than 1% decomposition) when protected from light.285 A change in color from pale yellow to pink or red is a sign of decomposition.285; 1093
Diluted solutions of dacarbazine may be stored for up to 8 hours at normal room temperature and light or up to 24 hours at 4°C.3720
Solutions should be visually inspected for particulate matter and discoloration prior to administration.3720
Immersion of a needle with an aluminum component in dacarbazine (Miles) 10 mg/mL resulted in no visually apparent unexpected reaction after seven days at 24°C.988
Light Effects
Administration of dacarbazine in a room illuminated only with a red photographic light apparently reduced the incidence of disagreeable side effects. The authors attributed this result to a reduced amount of photodegradation of dacarbazine.469
Multiple photodegradation products of dacarbazine have been identified and specific concentrations of each are crucially dependent on the pH of the solution.496
The effects of daylight and fluorescent light on dacarbazine (Bayer) 4 mg/mL in sodium chloride 0.9% were reported. Exposure to direct sunlight resulted in up to a 12% loss in 30 minutes, and a pink color formed in 35 to 40 minutes. Exposure to indirect daylight resulted in less than a 2% loss in 30 minutes. Solutions protected from light or exposed to fluorescent light lost about 4% of their dacarbazine in 24 hours.1248
The photostability of dacarbazine has been shown to increase with the addition of reduced glutathione at about 5 mg/100 mL.1829
Dacarbazine (Aventis) 11 mg/mL reconstituted with sterile water for injection in original amber glass vials stored at room temperature exposed to fluorescent light formed a visible precipitate and became yellow in 24 hours and turned pink after 96 hours. About 4% dacarbazine loss occurred in 96 hours, but precipitation limited the utility period to 24 hours. Formation of 2-azahypoxanthine, a potentially toxic decomposition product, was also noted. Under refrigeration protected from light, no precipitation was seen, but red discoloration appeared after 96 hours; little or no loss of dacarbazine occurred in seven days. Reconstituted dacarbazine was stated to be stable for 24 hours at room temperature under fluorescent light and 96 hours refrigerated in the dark.2386
Dacarbazine (Aventis) 1.4 mg/mL in dextrose 5% in PVC bags (Fresenius) was stored under a variety of temperature and light conditions. In PVC bags exposed to natural sunlight, the solution turned pink in six hours and red in 48 hours; it developed a precipitate in 96 hours. About 11% dacarbazine loss in three hours and 35% loss in 24 hours. Exposed to or protected from fluorescent light at room temperature and refrigerated, no visible changes occurred in seven days. At room temperature, dacarbazine losses were about 6% in 24 hours exposed to fluorescent light and 7% in 48 hours protected from light. Refrigerated samples protected from light exhibited little or no loss in seven days.2386
Simulated infusion of the dacarbazine 1.4-mg/mL solution through transparent (Baxter) and opaque (Codan) infusion tubing over about 110 minutes exposed to light resulted in the delivery of 94% (transparent tubing) and 98% (opaque tubing) of the dacarbazine.2386
Sorption
Dacarbazine (Medac) 0.64 mg/mL in sodium chloride 0.9% exhibited no loss due to sorption in polyethylene and PVC containers compared to glass containers over 48 hours at refrigeration temperature.2420; 2430
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