Phenytoin enzyme induction for management of supratherapeutic tacrolimus levels due to drug-drug interaction with nirmatrelvir/ritonavir: Case series and discussion.

This article focuses on the management of supratherapeutic tacrolimus levels caused by drug interactions between tacrolimus, an immunosuppressant used in solid organ transplant recipients, and nirmatrelvir/ritonavir, an antiviral combination approved for outpatient treatment of COVID-19. The case series describes five adult transplant patients who developed tacrolimus toxicity after receiving nirmatrelvir/ritonavir, and who were treated with oral phenytoin, a cytochrome P450 3A4 (CYP3A4) enzyme inducer, to accelerate tacrolimus metabolism and reduce toxic levels. The findings suggest that phenytoin may be a useful intervention for managing tacrolimus toxicity in this context, although careful monitoring and coordination with transplant teams are essential due to the complexity of drug interactions and risks of under- or over-immunosuppression. The report emphasizes the importance of proactive management and specialist consultation when prescribing nirmatrelvir/ritonavir to transplant recipients.