Division of Nephrology and Transplantation, Department of Medicine, University of Vermont Medical Center, Burlington, Vermont, USA.
Division of Nephrology and Transplantation, Department of Medicine, University of Vermont Medical Center, Burlington, Vermont, USA.
Transplant Proc. 2022 Jul-Aug;54(6):1557-1560. doi: 10.1016/j.transproceed.2022.04.015. Epub 2022 May 20.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a significant impact on communities and health systems. New antiviral medications against this disease have not been properly tested yet, and their efficiency, side effects, and drug-drug interactions are not entirely known. Organ transplant recipients receive immunosuppressive medications such as tacrolimus to prevent graft rejection. Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Many medications can either induce or inhibit this enzyme and affect the level. Awareness of possible drug-drug interactions is vital because tacrolimus levels should be kept within a specific narrow range determined by the recipient's immunologic risk. Underexposure increases the risk of graft rejection, whereas overexposure may lead to adverse effects. Paxlovid, a novel antiviral medication approved for emergency use to treat SARS-CoV-2, is a combination of nirmatrelvir and ritonavir, a cytochrome P450 34A inhibitor. In this case report, we present a case of a kidney transplant patient receiving tacrolimus treated with Paxlovid, leading to an abruptly high tacrolimus level, significant symptoms, treatment interruption, and acute kidney injury. We conclude that the drug-drug interaction between Paxlovid and tacrolimus is indeed robust and noteworthy and leads to high tacrolimus levels and its metabolites, adverse effects, and acute kidney injury. Physicians managing immunocompromised patients receiving tacrolimus should be aware of this significant drug-drug interaction and consider other options or reduction of daily tacrolimus dose during treatment in addition to timely monitoring of both tacrolimus levels and serum creatinine. Consulting with the transplant pharmacist is foremost in alerting for these interactions.
新型严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）大流行对社区和卫生系统产生了重大影响。针对这种疾病的新型抗病毒药物尚未经过适当的测试，其效率、副作用和药物相互作用尚不完全清楚。器官移植受者接受他克莫司等免疫抑制剂药物，以防止移植物排斥。他克莫司由细胞色素 P450 3A4 酶系统代谢。许多药物可以诱导或抑制这种酶，从而影响其水平。了解潜在的药物相互作用至关重要，因为他克莫司水平应保持在特定的窄范围内，该范围由受者的免疫风险决定。暴露不足会增加移植物排斥的风险，而暴露过度可能导致不良反应。Paxlovid 是一种新型的抗病毒药物，已获准紧急用于治疗 SARS-CoV-2，它是尼马曲韦和利托那韦的组合，利托那韦是细胞色素 P450 3A4 抑制剂。在本病例报告中，我们介绍了一名接受他克莫司治疗的肾移植患者使用 Paxlovid 的病例，导致他克莫司水平突然升高、出现明显症状、治疗中断和急性肾损伤。我们得出结论，Paxlovid 和他克莫司之间的药物相互作用确实显著且值得关注，会导致他克莫司水平及其代谢物升高、出现不良反应和急性肾损伤。管理接受他克莫司治疗的免疫功能低下患者的医生应意识到这种显著的药物相互作用，并考虑在治疗期间选择其他方案或减少他克莫司的日剂量，同时及时监测他克莫司水平和血清肌酐。与移植药剂师咨询是发现这些相互作用的首要方法。
