Drug Interactions between busulfan and deferoxamine

GENERALLY AVOID: Coadministration with iron chelating agents may result in an increase in the plasma concentrations and the risk of toxicity of busulfan. A reduction in the clearance of busulfan is suspected, although the mechanism is unknown. The interaction has been reported with the iron chelator deferasirox. A single-center, prospective, observational study examined 25 patients started on busulfan (3.2 mg/kg once daily with plans to adjust the dose based on therapeutic drug monitoring for a goal area under the curve (AUC) of 80 mg.h/L) as a myeloablative conditioning agent in preparation for allogenic hematopoietic stem cell transplant. Deferasirox (14 mg/kg/day) was started on day 1 of conditioning for transfusional iron overload until day 3 after the transplant. The use of deferasirox led to an increase in AUC of 35 to 40%, thought to result from a reduction in busulfan clearance by approximately one-third. There are also case reports documenting an increase in busulfan exposure and a reduction in busulfan clearance during coadministration with deferasirox. However, data are not available for deferoxamine.

MANAGEMENT: Until further information is available, it may be advisable to avoid concomitant use of busulfan with deferoxamine. Some manufacturers of busulfan recommend iron chelator therapy be discontinued well in advance of busulfan to avoid increased exposure to busulfan. The manufacturers of certain gene therapy agents also suggest the discontinuation of iron chelators (often approximately 7 days) before receipt of myeloablative therapy with busulfan. Consultation with product labeling and local or institutional guidelines may be appropriate for further recommendations.