Purpose: Cyclosporine A (CsA) and imatinib are both CYP3A4 and P-glycoprotein substrates. Concomitant use after hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (ALL) may therefore result in a pharmacokinetic interaction. Although case reports and a recent small study in children indeed suggested there is a relevant pharmacokinetic interaction, a larger study in adults is lacking. In this study, we assessed the presence and extent of this interaction in patients with CML or Ph+ ALL undergoing HSCT. Methods: From a large database containing data of all patients receiving HSCT in our center between 2005 and 2015, we selected 16 patients using this drug combination. The average dose-corrected CsA concentration was calculated before and after initiation of imatinib. Results: The average dose-corrected CsA concentration increased during imatinib use in all patients, on average by 94 % (p < 0.001). Based on measured drug concentrations, the CsA dosage needed to be reduced, on average, by 27 % after initiation of imatinib (p = 0.004). Conclusions: Imatinib significantly increases CsA concentrations in HSCT patients, putting these patients at increased risk of CsA toxicity. We recommend intensive monitoring of CsA concentrations after initiation of imatinib; a pre-emptive CsA dose reduction of 25 % might be considered.

Cyclosporine, Graft-versus-host disease, Hematopoietic stem cell transplantation, Imatinib
dx.doi.org/10.1007/s00228-016-2038-9, hdl.handle.net/1765/84605
European Journal of Clinical Pharmacology
Department of Internal Medicine

Atiq, F, Broers, A.E.C, Andrews, L.M, Doorduijn, J.K, Koch, B.C.P, van Gelder, T, & Versmissen, J. (2016). A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib. European Journal of Clinical Pharmacology, 72(6), 719–723. doi:10.1007/s00228-016-2038-9