Dactinomycin is available in vials containing 0.5 mg of drug with mannitol 20 mg.2945 Reconstitute with 1.1 mL of sterile water for injection without preservatives to yield a gold-colored solution containing approximately 0.5 mg/mL of dactinomycin.2945 The use of water for injection containing preservatives (e.g., benzyl alcohol, parabens) causes precipitation.2945
pH
The pH of the reconstituted solution is 5.5 to 7.1369
Trade Name(s)
Cosmegen
Dactinomycin is administered intravenously or by regional perfusion techniques.2945 The manufacturer states that only products diluted to concentrations greater than 10 mcg/mL are recommended for administration.2945 Extravasation should be avoided because of possible corrosion of soft tissue.377; 2945 An inline cellulose ester membrane filter should not be used for administration of dactinomycin.2945 (See Filtration.)
In the event of spills or leaks, the manufacturer recommends the use of trisodium phosphate 5% to inactivate dactinomycin.1200
Intact vials of dactinomycin should be stored at controlled room temperature and protected from light and humidity.2945 The clear, gold-colored, reconstituted solution is stable at room temperature; however, this solution contains no preservative so it has been suggested that unused portions of the injection be discarded.2945
Solutions of dactinomycin diluted to concentrations of 10 mcg/mL or greater in water for injection, sodium chloride 0.9%, or dextrose 5% demonstrated chemical stability for up to 10 hours at room temperature in both glass and PVC containers.2945 Solutions diluted to concentrations less than 10 mcg/mL, however, demonstrated significant losses.2945 The manufacturer recommends that the reconstituted and diluted product be used within 4 hours of reconstitution when stored at room temperature.2945
The drug is reported to be most stable at pH 5 to 7.1369 A 30-mcg/mL concentration at this pH range exhibits about a 2 to 3% loss in 6 hours at 25°C; at pH 9, an 80% loss occurs under these conditions.51
Dactinomycin, reconstituted according to the manufacturer’s instructions, was cultured with human lymphoblasts to determine whether its cytotoxic activity was retained. The solution retained cytotoxicity for 24 hours at 4°C and room temperature.1575
Filtration
Dactinomycin may exhibit considerable binding to cellulose acetate/nitrate (Millex OR) and polytetrafluoroethylene (Millex GV) filters.1249
Dactinomycin (MSD) 0.5 mg/L in dextrose 5%, sodium chloride 0.9%, and Ringer’s injection, lactated, was filtered over 12 hours through a 5-µm stainless steel depth filter (Argyle Filter Connector), a 0.22-µm cellulose ester membrane filter (Ivex-2 Filter Set), and a 0.22-µm polycarbonate membrane filter (In-Sure Filter Set). No significant reduction in potency due to binding was observed with the stainless steel filter. Approximately 25% of the drug delivered through the polycarbonate filter in the first 10 mL of solution was bound, but binding decreased rapidly thereafter, resulting in only 0.3% of the total delivered dose in 12 hours being bound.320
In contrast, filtration through the cellulose ester filter resulted in the binding of about 95 to 99% of the drug in the first 10 mL, with the total cumulative amount of drug bound in 12 hours being 13%. Approximately 50% of the bound drug was released by rinsing 3 times with 100 mL of the same intravenous solutions used in the admixtures.320
In another study, dactinomycin 0.5 mg/mL was injected as a bolus through a 0.2-µm nylon, air-eliminating filter (Ultipor, Pall) to evaluate the effect of filtration on simulated intravenous push delivery. Spectrophotometric evaluation showed that about 87% of the drug was delivered through the filter after flushing with 10 mL of sodium chloride 0.9%.809
Dactinomycin 4 to 50 mcg/mL exhibited a greater than 95% loss due to sorption to cellulose nitrate/cellulose acetate ester filters (Millex OR) and a 50 to 60% loss with polytetrafluoroethylene filters (Millex FG).1415; 1416
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