Cyclosporin is an immunosuppressive agent in allogeneic hematopoietic stem cell transplantation and its metabolism is strongly affected by concomitant drugs, including posaconazole which is now extensively used as anti-fungal prophylaxis post-allograft. We undertook a retrospective audit of 29 patients undergoing their first allograft who were receiving posaconazole at the time of transition from intravenous to oral cyclosporin. This group had a median initial oral cyclosporin dose of 2.58 mg/kg bd (range 1.75-3.95) and high incidence of cyclosporin-related toxicity was noted, requiring significant dose reductions such that by day 60 the media dose was 1.60 mg/kg bd (range 0.86-3.33). We subsequently amended our dosing protocol and analyzed a further 20 patients specifying an initial oral cyclosporin dose of 2.25 mg/kg bd and found this had little impact on toxicity or requirement for dose reductions. Starting doses of no greater than 2 mg/kg bd appear optimal to prevent toxicity in allograft recipients receiving concomitant posaconazole.
Keywords: Transplantation; cyclosporin; drug toxicity; posaconazole.