The effects of nirmatrelvir/ritonavir on tacrolimus levels in lung transplant recipients: A single-center study

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics Pub Date : 2023-12-06 DOI:10.1016/j.pupt.2023.102280

Xiaoxing Wang , Wenwen Du , Dan Zhang , Wenhui Chen , Xianbo Zuo

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引用次数: 0

Abstract

Background

Lung transplant recipients (LTRs) have a higher risk of hospitalization and mortality due to COVID-19 compared with the immunocompetent population. The use of nirmatrelvir/ritonavir (NR), an effective oral treatment for COVID-19, is quite challenging due to its potent drug-drug interactions with immunosuppressants and azole antifungals. As there are few clinical reports of the use of NR in LTRs, we measured tacrolimus levels in patients receiving NR in our hospital to improve safety when prescribing NR.

Methods

In total, 48 adult LTRs who received NR between November 19, 2022, and January 19, 2023, at China-Japan Friendship Hospital were retrospectively included and followed for 20 days after initiating NR. Tacrolimus was held at least 12 h before initiating NR and re-administered based on the trough levels after completing NR treatment. All concomitant medications, drug concentrations, laboratory results, and genotypes were recorded and analyzed.

Results

Most patients showed stable tacrolimus trough levels despite high individual variability. Four patients exhibited supratherapeutic trough levels of tacrolimus (more than 15 ng/mL). Two patients who received 0.5 mg of tacrolimus during NR treatment had trough levels below 3.0 ng/mL. In addition, we found that in 13 patients, the trough levels were 130% of baseline after cessation of tacrolimus, and logistic regression revealed that increased trough level was significantly associated with age more than 60 years.

Conclusions

NR can be safely used in LTRs with close monitoring of tacrolimus levels and appropriate dose adjustments. However, more attention should be paid to elderly patients, as NR may more severely affect their drug metabolism. Due to the limited sample size, further studies are needed to guide the optimal use of tacrolimus following treatment with NR and explore the risk factors significantly affecting the interactions between NR and tacrolimus.

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尼马瑞韦/利托那韦对肺移植受者他克莫司水平的影响：单中心研究

背景肺移植受者（LTR）与免疫功能正常人群相比，因 COVID-19 而住院和死亡的风险较高。尼马瑞韦/利托那韦（NR）是治疗 COVID-19 的一种有效口服药物，但由于其与免疫抑制剂和唑类抗真菌药之间存在强烈的药物相互作用，因此使用该药物具有相当大的挑战性。方法回顾性纳入2022年11月19日至2023年1月19日期间在中日友好医院接受NR治疗的48例成人LTR患者，并在开始接受NR治疗后随访20天。在开始 NR 治疗前至少 12 小时停用他克莫司，并在完成 NR 治疗后根据谷值重新给药。结果尽管个体差异很大，但大多数患者的他克莫司谷值稳定。四名患者的他克莫司谷值超过治疗水平（超过 15 纳克/毫升）。两名在 NR 治疗期间接受了 0.5 毫克他克莫司治疗的患者的谷值水平低于 3.0 纳克/毫升。此外，我们还发现有 13 名患者在停用他克莫司后，谷值水平达到了基线的 130%，逻辑回归显示谷值水平的升高与 60 岁以上的年龄显著相关。然而，由于 NR 可能会对老年患者的药物代谢产生更严重的影响，因此应更加关注老年患者。由于样本量有限，还需要进一步的研究来指导使用 NR 治疗后他克莫司的最佳使用方法，并探索对 NR 和他克莫司之间相互作用有显著影响的风险因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pulmonary pharmacology & therapeutics 医学-呼吸系统

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

42 days

期刊介绍： Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.