Purpose: Cyclosporine A (CsA) is the most widely used immunosuppressive agent after a hematopoietic stem cell transplantation (HSCT). Although recommendations for CsA dose conversion from intravenous to oral administration differ from 1:1 to 1:3, most studies did not consider the role of azole antifungals as an important confounder. Therefore, we assess the optimal conversion rate of CsA from intravenous to oral administration in HSCT recipients, taking into account the concomitant use of azole antifungals. Methods: We retrospectively included patients from a large database of 483 patients who underwent a HSCT and received intravenous CsA as part of the conditioning regimen and peritransplant immunosuppression. All patients were converted from intravenous to oral administration in a 1:1 conversion rate. We collected for each patient three CsA trough concentrations during intravenous and oral administration, directly before and after conversion to oral administration. Results: We included 71 patients; 50 patients co-treated with fluconazole, 10 with voriconazole, and 11 without azole co-medication. In patients with voriconazole, the dose-corrected CsA concentration (CsA concentration divided by CsA dosage) was not different between intravenous and oral administration (2.6% difference, p = 0.754), suggesting a CsA oral bioavailability of nearly 100%. In patients with fluconazole and without azole co-medication, the dose-corrected CsA concentration was respectively 21.5% (p < 0.001) and 25.2% (p = 0.069) lower during oral administration. Conclusions: In patients with voriconazole, CsA should be converted 1:1 from intravenous to oral administration. In patients with fluconazole and without azole co-medication, a 1:1.3 substitution is advised to prevent subtherapeutic CsA concentrations.

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Keywords Cyclosporine A, Dose conversion, Ferdows Atiq and Edon Hameli contributed equally to this work., Hematopoietic stem cell transplantation, Immunosuppression
Persistent URL dx.doi.org/10.1007/s00228-018-2434-4, hdl.handle.net/1765/105710
Journal European Journal of Clinical Pharmacology
Atiq, F, Hameli, E. (Edon), Broers, A.E.C, Doorduijn, J.K, van Gelder, T, Andrews, L.M, … de Winter, B.C.M. (2018). Converting cyclosporine A from intravenous to oral administration in hematopoietic stem cell transplant recipients and the role of azole antifungals. European Journal of Clinical Pharmacology, 1–7. doi:10.1007/s00228-018-2434-4