Optimized tacrolimus dosing strategy in kidney transplant recipients
receiving nirmatrelvir-ritonavir for COVID-19
Abstract
Kidney transplantation recipients (KTRs) represent a vulnerable
population for COVID-19 infection and severe disease.
Nirmatrelvir-ritonavir has demonstrated efficacy in treating COVID-19
among KTRs, which interacts with tacrolimus leading to a precipitous
increase in tacrolimus blood levels when co-administered, potentially
resulting in toxicity. This study conducted a Real-world analysis of
KTRs treated with nirmatrelvir-ritonavir for COVID-19 to investigate the
relationship between tacrolimus levels and dosing during and within 10
days post-discontinuation of nirmatrelvir-ritonavir. In the experimental
group, patients initiated tacrolimus at 20-25% of the baseline dose 48
hours after discontinuing nirmatrelvir-ritonavir, with daily increments
of 20-25% until the baseline dose was restored. Patients who did not
adhere to the experimental protocol were included in the control group.
Findings indicated that withholding tacrolimus 12 hours prior to
commencing nirmatrelvir-ritonavir maintained tacrolimus blood levels
above 83% of the baseline throughout the nirmatrelvir-ritonavir
treatment period. Compared to the control group, The experimental group
achieved target trough concentrations of tacrolimus more rapidly and
maintained a higher proportion within the therapeutic range (
p=0.029), and exhibited significantly lower rates of adverse
events ( p<0.001). This investigation provides a safe and
effective pharmacological strategy for KTRs infected with COVID-19,
enabling the safe co-administration of nirmatrelvir-ritonavir and
tacrolimus.