Tacrolimus Toxicity Induced by Nirmatrelvir/Ritonavir in a Renal Transplant Recipient Managed With Phenytoin: A Case Report and Literature Review.

INTRODUCTION

The COVID-19 pandemic has led to widespread use of nirmatrelvir/ritonavir in high-risk populations. Ritonavir, a strong CYP3A4 inhibitor, can significantly increase tacrolimus levels, causing toxicity in transplant recipients. This report presents a case of nirmatrelvir/ritonavir -induced tacrolimus toxicity in a kidney transplant patient, successfully managed with phenytoin, a CYP3A4 inducer.

CASE REPORT: A 63-year-old male kidney transplant recipient experienced malaise and hand tremors after nirmatrelvir/ritonavir treatment for mild COVID-19. Lab tests revealed ac1ute kidney injury and supratherapeutic tacrolimus levels (>60 ng/mL). Tacrolimus was discontinued, and hydration was initiated. Persistent toxicity required phenytoin, leading to rapid improvement. A renal biopsy showed no toxicity, and the patient was discharged without complications.

DISCUSSION: Among 51 reported cases of nirmatrelvir/ritonavir -induced tacrolimus toxicity, 13 used CYP3A4 inducers. This case highlights phenytoin's efficacy in reducing toxicity and protecting renal function. Timely initiation with a loading dose is crucial for optimal outcomes.

CONCLUSION

Early recognition and prompt management with hydration and CYP3A4 inducers, such as phenytoin, are essential in mitigating nirmatrelvir/ritonavir -associated tacrolimus toxicity.