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

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.

KEYWORDS:

• Nirmatrelvir/ritonavir
• tacrolimus
• drug–drug interaction
• acute renal failure
• disproportionality analysis
• FAERS

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Liu W contributed to the conception and design of the study. Qin F contributed to the analysis, interpretation, and manuscript writing. Qin F, Wang H, Li M and Zhuo S contributed to the literature search and data acquisition. Liu W and Qin F revised the manuscript. All authors gave final approval and agreed to be responsible for all aspects of the work.

Data availability statement

FDA Adverse Event Reporting System data are available at https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard (accessed on 10 February 2023).

Additional information

Funding

This paper was not funded.