Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series

Shawn P Griffin; Benjamin Lee; Jean Doh; Alexander R Paradyse; Deepa Jeyakumar; Zhaohui Arter; Hannah Nam; Emily Blodget; Julie Smith; Anitram Valek; Pongthep Vittayawacharin; Piyanuch Kongtim; Stefan O Ciurea

doi:10.1159/000534445

Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series

Acta Haematol. 2023 Oct 9:1-7. doi: 10.1159/000534445. Online ahead of print.

Authors

Shawn P Griffin^{1

2}, Benjamin Lee^{1

2}, Jean Doh², Alexander R Paradyse², Deepa Jeyakumar³, Zhaohui Arter³, Hannah Nam⁴, Emily Blodget⁴, Julie Smith³, Anitram Valek⁵, Pongthep Vittayawacharin^{3

6}, Piyanuch Kongtim³, Stefan O Ciurea³

Affiliations

¹ Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, California, USA.
² Department of Pharmacy, University of California Irvine Health, Orange, California, USA.
³ Division of Hematology Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine Health, Orange, California, USA.
⁴ Division of Infectious Diseases, Department of Medicine, University of California Irvine Health, Orange, California, USA.
⁵ Department of Nursing, Chao Family Comprehensive Cancer Center, University of California Irvine Health, Orange, California, USA.
⁶ Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

PMID: 38059378
DOI: 10.1159/000534445

Abstract

Introduction: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals.

Case presentations: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations.

Conclusion: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.

Keywords: Allogeneic hematopoietic stem cell transplantation; COVID-19; Case report; Drug-drug interaction; Nirmatrelvir/ritonavir; Tacrolimus.

Publication types

Case Reports