Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada.
The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Clin J Am Soc Nephrol. 2023 Jul 1;18(7):913-919. doi: 10.2215/CJN.0000000000000186. Epub 2023 Apr 26.
Nirmatrelvir/ritonavir has been shown to reduce the risk of coronavirus disease 2019 (COVID-19)-related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program.
Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up to 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on day 8) on the basis of the drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor-level monitoring was implemented. Outcomes, including tacrolimus-level changes, serum creatinine and AKI (defined as serum creatinine increase by 30%), and clinical outcomes were described globally and compared between algorithms.
Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first time point, 7 days after withholding of calcineurin inhibitor, and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44 (48%), and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 [4.0-6.2] µg/L versus 4.8 [4.3-5.7] µg/L, P = 0.70). There were no acute rejections or other complications.
Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_07_10_CJN0000000000000186.mp3.
奈玛特韦/利托那韦已被证明可降低 COVID-19 相关并发症风险，适用于高风险 COVID-19 重症患者。然而，由于与钙调神经磷酸酶抑制剂的药物相互作用复杂，移植受者人群中奈玛特韦/利托那韦的临床经验较为分散。我们描述了渥太华医院肾移植项目中奈玛特韦/利托那韦的临床经验。
纳入 2022 年 4 月至 6 月期间使用奈玛特韦/利托那韦的患者，并在治疗结束后 30 天内进行随访。他克莫司在停用 24 小时后，在最后一次服用奈玛特韦/利托那韦后 72 小时（第 8 天），根据前一天的药物水平恢复。根据药物水平，前 30 例患者在前 1 周内进行两次剂量调整，此后按需调整。随后，实施了一种简化的算法，减少钙调神经磷酸酶抑制剂水平监测的频率。总体描述了结果，包括他克莫司水平变化、血清肌酐和 AKI（定义为血清肌酐增加 30%），并比较了两种算法之间的结果。
51 例患者接受了奈玛特韦/利托那韦治疗。在首次检测、停用钙调神经磷酸酶抑制剂后 7 天和停止使用奈玛特韦/利托那韦后 2 天，44 例患者中有 17 例（39%）他克莫司水平处于治疗目标范围内，21 例（48%）低于治疗目标范围，6 例（14%）高于治疗目标范围。2 周后，55%的患者处于治疗范围内，23%的患者低于治疗范围，23%的患者高于治疗范围。标准和简化算法提供了相似的他克莫司水平（中位数分别为 5.2[4.0-6.2]µg/L和 4.8[4.3-5.7]µg/L，P=0.70）。没有发生急性排斥反应或其他并发症。
在开始使用奈玛特韦/利托那韦前一天开始停用他克莫司，并在治疗结束后 3 天恢复使用，结果导致许多患者出现低水平的超治疗范围，但治疗范围低的时间较短。AKI 发生率较低。该数据受到样本量小和随访时间短的限制。
本文包含一个播客，网址为：https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_07_10_CJN0000000000000186.mp3。
