Drug Interactions between busulfan and Exjade

GENERALLY AVOID: Coadministration with iron chelating agents, such as deferasirox, 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. 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 lead 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.

MANAGEMENT: Some manufacturers of busulfan recommend deferasirox 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 like deferasirox (often approximately 7 days) before receipt of myeloablative therapy with busulfan. However, other busulfan product labeling recommends close monitoring of busulfan's plasma concentration with dose adjustments, if needed, in patients who are or have recently been treated with deferasirox. Consultation with product labeling and local or institutional guidelines may be appropriate for further recommendations.