Abstract: FR-PO1021
Phenytoin to the Rescue! A Novel Approach to Tacrolimus Toxicity
Session Information
- Transplantation: Clinical - Pharmacology and Nonkidney Solid Organ Transplants
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Lynch, Kara, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Nguyen, Julia, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Watson, Maura A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Joshi, Megha Raj, Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction
Tacrolimus, a calcineurin inhibitor used for immunosuppression in organ transplant recipients, is metabolized via the cytochrome P-450 3A4 (CYP3A4) enzyme system with resultant increased risk for drug-drug interactions. Nirmatrelvir/ritonavir, a potent CYP3A4 inhibitor, can precipitate severe tacrolimus toxicity. We present a unique case where phenytoin, a known CYP3A4 inducer, was used in a novel way to reverse acute severe tacrolimus toxicity in a renal transplant patient.
Case Description
A 75-year-old male with deceased donor kidney transplant, was admitted to the medical intensive care unit for altered mental status, hyponatremia, hyperglycemia, acidosis and acute kidney injury (AKI). He presented with a supratherapeutic tacrolimus level >90 ng/mL, attributed to a drug-drug interaction following a course of nirmatrelvir/ritonavir for a COVID-19 infection. Despite stopping tacrolimus and nirmatrelvir/ritonavir and supportive care, his tacrolimus level remained undetectably high, causing a prolonged ICU course and a need for an alternate treatment approach. After initiation of phenytoin 200mg every 12 hours for 2 days, his tacrolimus levels decreased 40-60% with reversal of his encephalopathy and recovery of renal function.
Discussion
Ritonavir, a component of nirmatrelvir/ritonavir, strongly inhibits CYP3A4, causing reduced metabolism and accumulation of tacrolimus. Elevated tacrolimus levels can cause neurotoxicity, nephrotoxicity, and diabetic ketoacidosis, all of which occurred in our patient and resolved after a novel 2-day, low-dose phenytoin regimen. Phenytoin accelerates tacrolimus metabolism and case reports have reported efficacy in resolving symptomatic toxicity, but no standardized therapeutic protocol exists and evidence regarding effective dosing strategies are lacking. Our patient responded well to the shortest course and lowest dose phenytoin regimen thus far reported. This case adds needed evidence regarding best use practices for phenytoin in the treatment of tacrolimus toxicity.
The views expressed in this abstract are those of the author(s) and do not necessarily reflect the official policy of the Department of Defense or the United States Government.