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Proceed With Caution: Drug Interaction Complicates Use of Nirmatrelvir/Ritonavir in Kidney Transplant Recipients With COVID-19 谨慎进行:药物相互作用使尼马特里韦/利托那韦在COVID-19肾移植受者中的使用复杂化
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.053
S. Shailly, C. Miles, S. Westphal, K. Borghoff, A. Ma’ayah
Introduction: Kidney transplant recipients are at increased risk of severe COVID-19 infection due to poor response to vaccination and immunosuppression. Antiviral therapies are thus important to mitigate risk of severe disease. Nirmaltrelvir/ritonavir, an oral antiviral, has increasingly been used in higher risk patients with COVID-19. Unique to transplant patients is the risk of calcineurin inhibitor (CNI) drug interaction and potential for severe drug toxicity. Case Description: A 57-year-old male received a kidney transplant 8 months ago. Immunosuppression includes tacrolimus, mycophenolate, and prednisone, and he was fully vaccinated and boosted against SARS-CoV-2. He presented with headache, fevers, and body aches and COVID antigen test was positive. His primary care provider prescribed nirmatrelvir/ritonavir, and immunosuppression was continued. Two days later he developed nausea, vomiting, diarrhea, and fatigue prompting emergency evaluation. It was unclear if symptoms were drug-related or due to COVID-19 infection. Given the high risk of severe COVID-19, nirmatrelvir/ritonavir was continued, and tacrolimus was held. Two days later, tacrolimus level was checked and resulted at 75.6 ng/mL, complicated by acute kidney injury. He was admitted, treated with intravenous fluids and phenytoin to enhance CNI metabolism. Symptoms and graft function improved, and tacrolimus level decreased but remained high 2 days later (54 ng/mL). Tacrolimus remained on hold at discharge and was restarted when level normalized. Discussion(s): Nirmatrelvir inhibits Mpro, a protease enzyme required for SARS-CoV-2 replication. As a potent inhibitor of CYP3A, nirmatrelvir/ritonavir may interact with drugs metabolized through this pathway, including CNIs. This patient's tacrolimus level was severely elevated even after 2 days of drug cessation leading to toxicity and hospitalization. Use of nirmatrelvir/ritonovir with CNIs requires extreme caution. The antiviral benefit may be opposed by risks incurred through drug interaction. If used, we recommend holding or reducing the CNI dose and close monitoring of levels. Providers and patients should be educated about this interaction, and alternative treatments may be preferable.
导言:肾移植受者由于对疫苗接种和免疫抑制反应不佳,发生COVID-19严重感染的风险增加。因此,抗病毒治疗对于减轻严重疾病的风险非常重要。口服抗病毒药物尼马尔特里韦/利托那韦越来越多地用于高风险的COVID-19患者。移植患者特有的风险是钙调磷酸酶抑制剂(CNI)药物相互作用和潜在的严重药物毒性。病例描述:一名57岁男性,8个月前接受肾脏移植手术。免疫抑制包括他克莫司、霉酚酸盐和强的松,他接种了全面疫苗,增强了对SARS-CoV-2的抵抗力。患者出现头痛、发热、身体疼痛等症状,新冠病毒抗原检测呈阳性。他的初级保健医生开了尼马特韦/利托那韦,并继续免疫抑制。两天后,他出现恶心、呕吐、腹泻和疲劳,需要进行紧急评估。目前尚不清楚这些症状是与药物有关还是与COVID-19感染有关。鉴于COVID-19严重风险高,继续使用尼马特韦/利托那韦,保留他克莫司。2 d后检查他克莫司水平,75.6 ng/mL,并发急性肾损伤。他入院接受静脉输液和苯妥英钠治疗,以增强CNI代谢。症状和移植物功能改善,他克莫司水平下降,但2天后仍保持在高位(54 ng/mL)。他克莫司在出院时保持搁置状态,当水平恢复正常时重新开始。讨论:Nirmatrelvir抑制Mpro,一种SARS-CoV-2复制所需的蛋白酶。作为CYP3A的有效抑制剂,nirmatrelvir/ritonavir可能与通过该途径代谢的药物相互作用,包括CNIs。该患者停药2天后他克莫司浓度仍严重升高,导致中毒和住院。使用尼马特利韦/利托诺韦与cni需要非常谨慎。抗病毒效果可能与药物相互作用产生的风险相反。如果使用,我们建议保持或减少CNI剂量并密切监测水平。提供者和患者应该了解这种相互作用,替代治疗可能更可取。
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引用次数: 0
Stellate Ganglion Block for refractory Raynaud’s Phenomenon- A Case Report 难治性雷诺现象的星状神经节阻滞1例报告
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.007
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引用次数: 0
A Case of Groove Pancreatitis Presenting with Intermittent Gastric Outlet Obstruction 以间歇性胃出口梗阻为表现的沟型胰腺炎1例
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.048
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引用次数: 0
Isomorphic Inframammary Erosive Lichen Planus After Radiation Treatment Progressing to Squamous Cell Carcinoma 放射治疗进展为鳞状细胞癌后同构乳下糜烂性扁平苔藓
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.060
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引用次数: 0
Up-Regulation of Tumor Suppressor MicroRNA LET-7 in Inflammatory Bowel Disease is a Novel Molecular Marker for Induction of Disease Remission 肿瘤抑制MicroRNA LET-7在炎症性肠病中的上调是诱导疾病缓解的新分子标志物
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.008
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引用次数: 0
Potential Prognostic Determinants for FET::CREB Fusion Positive Intracranial Mesenchymal Tumors FET::CREB融合阳性颅内间充质肿瘤的潜在预后决定因素
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.022
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引用次数: 0
Giant Cell Tumor of Soft Tissue in the Dermis 真皮软组织巨细胞瘤
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.063
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引用次数: 0
Improving Safety Through Accurate and Patient-centered Insulin Discharge Instructions 通过准确和以患者为中心的胰岛素出院指南提高安全性
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.026
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引用次数: 0
Invasive Gastrointestinal Mucormycosis in Inflammatory Bowel Disease 炎症性肠病的侵袭性胃肠道毛霉病
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.049
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引用次数: 0
Clinically Significant Hypotension in Patients Undergoing Thoracoscopic Lobectomy: A Single-center, Retrospective Analysis of Thoracic Epidural Analgesia Versus Liposomal Bupivacaine Intercostal Nerve Blockade 胸腔镜肺叶切除术患者的临床显著性低血压:单中心回顾性分析胸椎硬膜外镇痛与布比卡因脂质体肋间神经阻断
Pub Date : 2023-06-01 DOI: 10.32873/unmc.dc.gmerj.5.1.011
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引用次数: 0
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Graduate Medical Education Research Journal
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