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“一次拯救一名移植患者的生命:尼马曲韦/利托那韦”。

"Saving lives with nirmatrelvir/ritonavir one transplant patient at a time".

机构信息

Division of Infectious Diseases, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.

Department of Transplant, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.

出版信息

Transpl Infect Dis. 2023 Apr;25(2):e14037. doi: 10.1111/tid.14037. Epub 2023 Feb 27.

Abstract

BACKGROUND

Solid organ transplant (SOT) recipients are at risk of complications from COVID-19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID-19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring.

METHODS

We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy.

RESULTS

Of 47 patients identified, 28 were receiving tacrolimus and had follow-up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS-CoV-2 mRNA vaccine. Patients had mild-moderate COVID-19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1-6.7), while median follow-up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7-11.5, p = 0.0017). Median baseline and follow-up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02-1.39) and 1.21 mg/dL (interquartile range 1.02-1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID-19 in the follow up period.

CONCLUSION

While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring.

摘要

背景

实体器官移植(SOT)受者有 COVID-19 并发症的风险。尼马曲韦/利托那韦(Paxlovid)可降低 COVID-19 的死亡率,但在接受钙调神经磷酸酶抑制剂(CI)的患者中禁用,后者依赖细胞色素 p4503A(CY3PA)。在这项研究中,我们旨在展示在协调药物管理和有限的他克莫司谷浓度监测的情况下,向接受 CI 的 SOT 受者给予尼马曲韦/利托那韦的可行性。

方法

我们回顾了 2022 年 4 月 14 日至 11 月 1 日期间接受尼马曲韦/利托那韦治疗的成年 SOT 受者,并评估了治疗后他克莫司谷浓度和血清肌酐的变化。

结果

在确定的 47 名患者中,有 28 名正在接受他克莫司治疗,并进行了随访实验室检查。患者的平均年龄为 55 岁,17 名(61%)接受了肾移植,23 名(82%)接受了三剂或更多剂 SARS-CoV-2 mRNA 疫苗。患者患有轻度至中度 COVID-19,在症状出现后 5 天内开始接受尼马曲韦/利托那韦治疗。中位基线他克莫司谷浓度为 5.6ng/mL(四分位距 5.1-6.7),而中位随访他克莫司谷浓度为 7.8ng/mL(四分位距 5.7-11.5,p=0.0017)。中位基线和随访血清肌酐水平分别为 1.21mg/dL(四分位距 1.02-1.39)和 1.21mg/dL(四分位距 1.02-1.44,p=0.3162)。一名肾移植受者的随访肌酐水平高于基线的 1.5 倍。在随访期间,没有患者因 COVID-19 住院或死亡。

结论

虽然尼马曲韦/利托那韦的给药导致他克莫司浓度显著增加,但这并没有导致明显的肾毒性。即使在有限的他克莫司谷浓度监测下,SOT 受者的早期口服抗病毒治疗也是可行的,通过药物管理。

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