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
Issued Date
2023-01-01
Resource Type
ISSN
00015792
eISSN
14219662
Scopus ID
2-s2.0-85179112618
Pubmed ID
38059378
Journal Title
Acta Haematologica
Rights Holder(s)
SCOPUS
Bibliographic Citation
Acta Haematologica (2023)
Suggested Citation
Griffin S.P., Lee B., Doh J., Paradyse A.R., Jeyakumar D., Arter Z., Nam H., Blodget E., Smith J., Valek A., Vittayawacharin P., Kongtim P., Ciurea S.O. 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 Haematologica (2023). doi:10.1159/000534445 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91543
Title
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
Author's Affiliation
Other Contributor(s)
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.