• Bram C Agema, Kim Vrielink, Esther Oomen-de Hoop, Frank van Tienen, GeijtemanEric C TECTDepartment of Medical Oncology (B.C.A., K.V., E.O.D.H., F.V.T., E.G., C.C.D.V.D.R., S.L.W.K., A.W.O., R.H.J.M.), Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Carin C D Van der Rijt, KochBirgit C PBCPDepartment of Clinical Pharmacy (B.C.P.K., S.L.W.K.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group (B.C.P.K.), Erasmus University Medical Center, Rotterdam, The Netherlands., Stijn L W Koolen, Astrid W Oosten, and MathijssenRon H JRHJDepartment of Medical Oncology (B.C.A., K.V., E.O.D.H., F.V.T., E.G., C.C.D.V.D.R., S.L.W.K., A.W.O., R.H.J.M.), Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands..
• Department of Medical Oncology (B.C.A., K.V., E.O.D.H., F.V.T., E.G., C.C.D.V.D.R., S.L.W.K., A.W.O., R.H.J.M.), Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Clinical Pharmacy (B.C.P.K., S.L.W.K.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Rotterdam Clinical Pharmacometrics Group (B.C.P.K.), Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: b.agema@erasmusmc.nl.
• J Pain Symptom Manage. 2024 Dec 1; 68 (6): e491e499e491-e499.

ContextSubcutaneous (SC) administration of fentanyl allows for rapid dose titration to treat urgent cancer-related pain. After establishing the optimal fentanyl dose, patients typically rotate towards transdermal (TD) fentanyl patches. Continuing the SC fentanyl up to 12h after application of the patch led to elevated fentanyl concentrations and fentanyl-related toxicities. Based on these findings, and simulations using a pharmacokinetic (PK) model, SC fentanyl administration was discontinued immediately following the application of the patch.ObjectivesTo validate the fentanyl rotation schedule by assessing the PK equivalence in fentanyl exposure before and after rotation.MethodsPK samples and clinical data were prospectively collected from 12 hours prior to rotation until 12 hours after rotation in patients with cancer-related pain undergoing fentanyl rotation.ResultsBetween December 2021 and September 2023, 29 evaluable patients were enrolled in the study. The 90% confidence interval (CI) of the geometric mean ratio between the post- over pre-rotation area under the curve (AUC) fell within the prespecified 0.8-1.25 equivalence interval (90% CI 1.05-1.16). Patient-reported intensity of both nausea (P = 0.047) and transpiration (P = 0.034) decreased post-rotation. Pain intensity and other adverse events did not differ significantly pre and post-rotation. One patient needed adjustment of opioid therapy 40 hours after rotation due to fentanyl-related toxicities.ConclusionThe updated rotation scheme, implying a 1:1 dose conversion and discontinuation of SC fentanyl directly after rotation, resulted in equivalent fentanyl exposure pre and post-rotation. Moreover, the dosing regimen showed to be safe and efficacious during rotation. The new dosing regimen when rotating from SC to TD fentanyl can be effectively and safely implemented in routine palliative care.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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