Nirmatrelvir/利托那韦是一种治疗COVID-19的药物,具有抗SARS-CoV-2活性,还有利托那韦,维持血液水平的助推器。已知利托那韦是细胞色素P4503A(CYP3A)的有效抑制剂,以及与CYP3A代谢药物的相互作用,如免疫抑制剂他克莫司,可能会有问题。利托那韦的CYP3A的抑制是不可逆的,由于共价结合,其抑制作用有望持续到被新的CYP3A取代。这里,我们报告了一个病例,尼马特雷韦/利托那韦和他克莫司的组合导致毒性他克莫司血水平。一名他克莫司治疗系统性红斑狼疮(SLE)的患者患上了COVID-19,并接受了尼马特雷韦/利托那韦的处方。开始尼马特雷韦/利托那韦和他克莫司的组合后,患者的他克莫司血液水平变得异常高,导致这些药物因他克莫司毒性症状而停药。即使在利托那韦血液水平低于检测限之后,他克莫司血液水平的下降被延迟.利托那韦的CYP3A抑制持续存在,即使其血液浓度降低,强调在开始尼马特雷韦/利托那韦治疗之前需要仔细考虑合并用药。调整或停止可能是必要的。
Nirmatrelvir/
ritonavir is a treatment for COVID-19 consisting of nirmatrelvir, which has anti-SARS-CoV-2 activity, and
ritonavir, a booster to maintain blood levels. Ritonavir is known to be a potent inhibitor of cytochrome P450 3A (CYP3A), and interactions with CYP3A-metabolized drugs, such as the immunosuppressant tacrolimus, can be problematic.
Ritonavir\'s inhibition of CYP3A is irreversible due to covalent binding, and its inhibitory effects are expected to persist until replaced by new CYP3A. Here, we report a
case where the combination of nirmatrelvir/
ritonavir and tacrolimus resulted in toxic tacrolimus blood levels. A patient on tacrolimus for systemic lupus erythematosus (SLE) developed COVID-19 and was prescribed nirmatrelvir/ritonavir. After starting the combination of nirmatrelvir/ritonavir and tacrolimus, the patient\'s tacrolimus blood levels became abnormally high, leading to the discontinuation of these drugs due to symptoms of tacrolimus toxicity. Even after
ritonavir blood levels had fallen below the detection limit, the decline in tacrolimus blood levels was delayed. The CYP3A inhibition of ritonavir persists even when its blood concentration decreases, emphasizing the need for careful consideration of concomitant medications before starting nirmatrelvir/ritonavir therapy. Adjustments or discontinuation may be necessary.