Impact of Paxlovid on Tacrolimus Concentration in Kidney Transplant Patients: A Retrospective Observational Study

Abstract

Kidney transplant recipients, reliant on lifelong immunosuppressive therapy, face potential drug interactions with emerging treatments such as paxlovid. This study aims to provide guidance for safe administration by examining the impact of paxlovid on tacrolimus levels in kidney transplant recipients. Seven kidney transplant patients who received paxlovid between December 2022 and August 2023 were included for retrospective analysis. Tacrolimus concentration changes were investigated both during and after the administration of paxlovid. Genetic testing for CYP3A5 polymorphisms assessed individual responses. The patient's treatment process was divided into four phases according to the paxlovid administration and the Tacrolimus trough level. The variation of tacrolimus valley concentration, concentration-to-dose ratios (C/D), and creatinine values in different periods were subsequently described and analyzed. The results indicate that tacrolimus levels increased significantly after receiving paxlovid, peaking on day two with a median trough level of 21.8 ng/mL. Prior to the administration of paxlovid, the median C/D value was 6.8 times higher (903.1 to 132.5). Once the paxlovid was stopped, the C/D value and trough level progressively returned to their preadministration levels. Importantly, no graft rejections, adverse events, or neurotoxicity were noted. The levels of creatinine remained stable. During paxlovid treatment, patients adhered to a modified tacrolimus regimen and progressively resumed baseline dosage. In summary, this is the first study to indicate a significant influence of paxlovid on tacrolimus levels in Chinese patients undergoing kidney transplantation. During paxlovid treatment, careful observation and tailored tacrolimus management are crucial to guarantee safe administration and circumvent negative consequences.