Drug–drug interaction of Nirmatrelvir/ritonavir and tacrolimus: A potential risk disproportionality analysis of nephrotoxicity from COVID-19 reports in FAERS

Abstract

ABSTRACT Background Nirmatrelvir/ritonavir is a new oral antiviral agent for COVID-19, and tacrolimus is a widely used immunosuppressant. Drug–drug interaction between Nirmatrelvir/ritonavir and tacrolimus is expected. However, information regarding the drug–drug interaction in a real-world setting is limited. We aim to evaluate drug–drug interaction between tacrolimus and Nirmatrelvir/ritonavir and perform a disproportionality analysis to assess the potential risk of nephrotoxicity due to their combination for COVID-19 treatment based on the FAERS database. Research design and methods Disproportionality analysis was performed using the reporting odds ratio (ROR) method, and subset analysis was conducted based on the background of COVID-19 drugs combined with tacrolimus more than 10 times. Results In disproportionality analysis, combination of Nirmatrelvir/ritonavir and tacrolimus was significantly associated with acute kidney injury (41.13%), serum creatinine increased (14.18%), renal failure (2.84%), and renal impairment (2.84%). These positive signals of acute kidney injury and serum creatinine increased still strongly retained in subset analysis. No similar positive signals were detected in Nirmatrelvir/ritonavir-single group. Only in Cilgavimab/Tixagevimab-tacrolimus group and Remdesivir-tacrolimus group, acute kidney injury was recognized as weakly positive signals and disappeared in subset analysis. Conclusions The study results show significant drug–drug interaction between Nirmatrelvir/ritonavir and tacrolimus and confirm that their combination for COVID-19 treatment greatly increases risk of acute kidney injury.