Can Trisenox® be prepared in the same way as other anti-cancer drugs?
Trisenox® (arsenic trioxide) is an anti-cancer drug used in the treatment of acute promyelocytic leukaemia in relapse or resistant to other treatments.
We conducted a feasibility study on the preparation of this product, using bibliographical research and data supplied by the INRS (National Institute for Research and Safety) and by working doctors.
We were able to identify certain critical points: toxic redox reactions and unsuitable product packaging.
The rate of evaporation for arsenic trioxide (As2O3) is negligible at 20°C, the working temperature in controlled environments, but a dangerous concentration of these particles in suspension in the air can nonetheless be reached rapidly.
Moreover in the presence of reducing agents, such as certain other cytotoxic compounds, this gas can be reduced to arsenic, and may even produce arsine (AsH3), a highly toxic gas which can cause digestive problems, confusion and vertigo. Quartz filters can be impregnated with doses of gaseous arsenic trioxide and arsine, but these are not available commercially. The oxidation reaction of arsenic trioxide can be explosive. Is there a risk of explosion with the peracetic acid? Should we establish a latency period between the time the product leaves the sterilising air lock and the moment the technician handles it?
In seeking to avoid cross-contamination, is it sufficient to prepare these products at the end of a working session and following forced ventilation and cleaning of the work station? In this respect preparation in a closed system may be useful, but the packaging of Tirsenox in glass phials makes this impossible.
Taking these critical issues and constraints into account, it would seem arsenic trioxide cannot be prepared like any other cytotoxic product. As use of Trisenox ® is becoming more and more common, we feel it is now necessary to establish specific preparation protocols and properly adapted packaging solutions in order to ensure the safety of technicians handling the product and prevent any impact on the controlled environment.