Effect of Posaconazole on Cyclosporine Blood Levels and Dose Adjustment in Allogeneic Blood and Marrow Transplant Recipients

The posaconazole prescribing information recommends an upfront cyclosporine dose reduction upon initiation of posaconazole prophylaxis. We examined this recommendation in the early phase of allogeneic transplantation, where cyclosporine levels po-tentially becoming subtherapeutic following upfront dose reduction would be deleterious to transplant outcome. Our data show that while posaconazole leads to an increase in cyclosporine levels, subsequent cyclosporine dose reduction can be safely guided by therapeutic drug monitoring and is not required upfront. Therefore, the current recommendationmay be modified. Posaconazole is a novel triazole with broad-spectrum antifun-gal activity and a favorable toxicity profile (4, 7) that is cur-rently approved for primary antifungal prophylaxis in allogeneic blood and marrow transplantation (allo-BMT) recipients with graft-versus-host disease (GVHD) (18). Posaconazole prophy-laxis in allo-BMT recipients is normally administered in combi-nation with immunosuppressive drugs for GVHD prophylaxis and/or treatment, most commonly cyclosporine (CsA). On the basis of its CYP3A4-inhibitory activity, posaconazole increases the exposure to CsA, warranting a recommendation for close moni-toring of blood CsA levels and subsequent CsA dose adjustment