Optimizing immunosuppressant regimens and therapeutic drug monitoring in solid organ transplant recipients with COVID-19: A multicenter retrospective study

doi:10.5246/jcps.2025.12.083

Journal of Chinese Pharmaceutical Sciences ›› 2025, Vol. 34 ›› Issue (12): 1101-1113.DOI: 10.5246/jcps.2025.12.083

• Original articles • Previous Articles

Optimizing immunosuppressant regimens and therapeutic drug monitoring in solid organ transplant recipients with COVID-19: A multicenter retrospective study

Hui Yang¹^,⁸^,^#, Ying Zhang⁷^,^#, Kuifen Ma²^,⁸^,^#, Xiangduan Liu⁴^,⁸^,^#, Jiaojiao Chen⁵^,^#, Ying Wang⁴, Ying Zhu¹, Qing Qian⁶^,⁸^,^*(), Wenjing Hou³^,⁸^,^*(), Zhuoling An¹^,^*()

¹ Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
² Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 311500, Zhejiang, China
³ Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
⁴ Department of Pharmacy, Fifth Clinical College of Henan University of Traditional Chinese Medicine (Zhengzhou People’s Hospital), Zhengzhou 450000, Henan, China
⁵ Yantai Yuhuangding Hospital, Yantai 264001, Shandong, China
⁶ The First People’s Hospital of Changzhou, Changzhou 213003, Jiangsu, China
⁷ Department of Pharmacy, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China
⁸ National Alliance of Transplant Pharmacists, Hangzhou 311500, Zhejiang, China

Received:2025-08-07 Revised:2025-08-14 Accepted:2025-09-27 Online:2025-12-31 Published:2025-12-31
Contact: Qing Qian, Wenjing Hou, Zhuoling An
About author:
^# They contributed equally to this manuscript.

Abstract

Abstract:

Nirmatrelvir-ritonavir, while effective against COVID-19 in solid organ transplant recipients, poses significant interactions with immunosuppressive agents. This study aimed to establish clinical recommendations for immunosuppressive drug adjustment strategies during nirmatrelvir-ritonavir therapy. We enrolled solid organ transplant recipients receiving long-term immunosuppressive therapy who underwent short-term nirmatrelvir-ritonavir treatment for SARS-CoV-2 infection across five hospitals between December 2022 and June 2023. Continuous variables were reported as medians with interquartile ranges, and categorical variables as counts with percentages. All analyses were conducted using Python 3.12. A total of 103 recipients were included. Among 86 patients on tacrolimus, drug concentrations remained most stable when tacrolimus was discontinued within 24 h prior to nirmatrelvir-ritonavir initiation. Co-administration led to marked increases in tacrolimus levels, with 62.5% of patients experiencing > 50% elevations. Delaying discontinuation beyond 24 h increased the proportion of patients with > 50% declines in concentration (26.67%). Gradual reintroduction at 30%–60% of the original dose within 3–4 d post-therapy consistently stabilized tacrolimus levels, emphasizing the need for close blood concentration monitoring. In 11 cyclosporine-treated patients, one who reduced the dose to < 20% experienced a > 50% increase in concentration, while others who discontinued cyclosporine saw > 50% decreases. Resumption of cyclosporine at reduced or original doses between days 2 and 5 generally restored stable concentrations. For nine patients receiving sirolimus, no extreme fluctuations in drug levels were observed. Based on these findings, we recommend discontinuing tacrolimus 24 h before initiating nirmatrelvir-ritonavir, followed by reintroduction at 30%–60% of the baseline dose within 3–4 d, alongside routine blood level monitoring. For patients on cyclosporine or sirolimus, temporary discontinuation prior to antiviral therapy and dose adjustments guided by post-therapy drug levels appear to be safe and effective strategies.

Key words: Nirmatrelvir/Ritonavir, Solid organ transplant recipients, COVID-19, Immunosuppressive drugs

Supporting:

Hui Yang, Ying Zhang, Kuifen Ma, Xiangduan Liu, Jiaojiao Chen, Ying Wang, Ying Zhu, Qing Qian, Wenjing Hou, Zhuoling An. Optimizing immunosuppressant regimens and therapeutic drug monitoring in solid organ transplant recipients with COVID-19: A multicenter retrospective study[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(12): 1101-1113.

Figures/Tables 6

Table 1. Baseline characteristics of solid organ transplant recipients using nirmatrelvir/ritonavir.

Table 2. The regimen and concentration of immunosuppressants used by patients during COVID-19 infection.

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Optimizing immunosuppressant regimens and therapeutic drug monitoring in solid organ transplant recipients with COVID-19: A multicenter retrospective study

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