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

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.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.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.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.