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P.041 Switching from Ciclosporin to Tacrolimus as De Novo Calcineurin Inhibitor in Lung Transplantation: First Results of a Multidisciplinary Quality Assurance Project

Mace Matthew Schuurmans, Switzerland

Medical Director
Lung Transplant Program
University Hospital Zurich

Abstract

Switching from ciclosporin to tacrolimus as de novo calcineurin inhibitor in lung transplantation: first results of a multidisciplinary quality assurance project

Mace Schuurmans1, Eirini Chatzidaki1, Jerome Bonzon2, Lucas Hoyos Mejia3, Florian Fehlmann 3, Dominik W Damm1, Isabelle Opitz3, György Lang 3, René Hage1.

1Pulmonology, University Hospital Zurich, Zurich, Switzerland; 2Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland; 3Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland

Introduction: For three decades, the first choice calcineurin inhibitor (CNI) in our transplant center has been Ciclosporin. Most transplant centers worldwide use Tacrolimus (Tac) as the first choice CNI and favorable results from the ScanCLAD study (Dellgren 2024 Lancet Resp Med) support this practice. Starting January 2023 we changed our first choice CNI to Tac and made a special effort to address all issues arising in the first months after this change by a multidisciplinary team approach. Our audit aims to analyze our experience with Tac in the first year and document the implications on our daily management of lung transplant recipients by including the insights in our standard operating procedure documents (SOPs). 
Methods: We retrospectively performed an interim audit analysis of our experience with Tac in the first year, assessing adaptation of co-medication, dosing regimens, and complications (tacrolimus drug level deviations: overdosed levels defined as ≥20 ng/mL and intoxication as ≥25 ng/mL). Our immunosuppressive strategy has been published previously (Schuurmans 2023 Medicina). 
Results: In the first year, 37 lung transplantations were performed, all receiving Tac as first choice CNI. Forteen patients had Tac levels ≥20 ng/mL of which 7 patients had a level ≥ 25. 13/14 overdosed patients were documented in the first 3 months posttransplant; one patient was overdosed five months posttransplant. 9/14 patients experience an acute kidney injury, none requiring extended duration dialysis. 3/14 patients experienced transient neurological symptoms. No patient experienced a posterior reversible encephalopathy. All episodes were resolved without severe sequelae. The frequency of infections and allograft dysfunctions including acute rejections are still being evaluated. Bronchoscopic evaluations included transbronchial biopsies and cryobiopsies. Two SOPs were created to improve drug dosing and co-medication choice and timing. The change from immediate-release Tac to extended-release Tac was delayed by 1 month based on our analysis in weekly interdisciplinary case discussions with the pharmacology team.
Conclusion: Despite elevated Tac drug levels in a relevant proportion of our recent lung transplant recipients the multidisciplinary approach resulted in a rapid learning experience for the entire team generating two SOPs which led to improved Tac dosing regimens, co-medication, and awareness of adverse outcomes of Tac overdosing. Severe sequelae were avoided by this approach. The analysis is still ongoing.

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