Impact of voriconazole/posaconazole on CsA in paediatric allogeneic haematopoietic stem cell transplantation recipients: A real‐world study

Abstract Aims The aim of this study is to investigate the key factors influencing the extent of DDI between cyclosporine A (CsA, GtoPdb Ligand ID: 2162) and voriconazole (VCZ, GtoPdb Ligand ID: 6424)/posaconazole (PCZ, GtoPdb Ligand ID: 6426) in Chinese paediatric allo‐HSCT recipients and to establish evidence‐based dose adjustment strategies. Methods One‐hundred‐four children were enrolled and already taking stable doses of oral CsA when voriconazole or posaconazole was initiated. Evaluate the CsA dose and body weight‐adjusted dose‐normalized concentration (C/D) required to achieve therapeutic trough concentration (Cmin) before and after initiation of voriconazole or posaconazole. Results CsA C/D increased by 173.37% during VCZ co‐therapy and 132.90% during PCZ co‐therapy. The magnitude of change in CsA C/D was significantly associated with CYP2C19 (GtoPdb Enzyme ID: 1043) genotype and PCZ Cmin. For maintaining therapeutic CsA exposure, the required percentage reduction in CsA dose varied according to CYP3A5 (GtoPdb Enzyme ID: 1040) genotype and age. In the VCZ group, dose reductions ranged from 22.22% to 43.47% across age and CYP3A5 genotype subgroups. In the PCZ group, dose reductions ranged from 12.77% to 33.34% across corresponding subgroups. Conclusion CYP2C19 genotype and PCZ Cmin independently affect the magnitude of the DDI between CsA and VCZ/PCZ in paediatric allo‐HSCT patients, and CYP3A5 genotype and age of children should be integrated to guide individualized CsA dose reduction when co‐administered with VCZ or PCZ.