Microwave freeze-thaw treatment of dose-banded cytotoxics injectable drugs: a review of the literature from 1980 to 2011.

INTRODUCTION: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of this review is to collect information about the stability of cytotoxic and hazardous drugs after this treatment.

METHODS: The scientific literature about drug stability studies was reviewed. The data describe the name of the drug, the manufacturer, the final concentration, the temperature and time of freezing storage, type of microwave oven, the thawing power, the measurement, the method and the results after treatment and final long-term storage at 5±3°C.

RESULTS: From 1980 to 2011, nine drugs (cyclophosphamide, cytarabine, daunorubicine, doxorubicine, epirubicine, fluorouracile, ganciclovir, methotrexate sodium, mitomycine C) were studied after MFTT and the results were presented in 10 publications. The storage freezing temperature ranged from -15°C to -30°C, the time storage from 14 to 364 days, the thaw from moderate to full power. High performance liquid chromatography is mainly used to measure drug concentrations. All drugs are stable during and after the treatment. However, mitomycine needs to be stored at -30°C. The long-term stability after MFTT was evaluated only for the ganciclovir after 7 days, and for fluorouracile after 28 days. The concentration of the seven drugs was measured after one to 11 freezing-thawing cycles with a loss below 5%.

CONCLUSIONS: This review can help the hospital pharmacist to take in charge the productions of nine dose-banded ready-to-use injectable cytotoxic and hazardous drugs. Freezing enhances their long-term stability without altering their chemical stability. Validated microwave thawing reduces the time of defrosting of these drugs at the studied concentrations.