Tacrolimus Induced Organ Failure: Reversal by Activation of the Cytochrome P450-3a System

Abstract

Tacrolimus is the cornerstone component of all immunosuppressive regimens. Despite its long record of use, very little is known about its acute toxicity syndrome. We describe five patients with acute organ failure, involving both native and transplanted organs, which was reversed by inducing the cytochrome P450-3A system. In all patients, the causative drug was stopped and phenytoin was given intravenously to accelerate tacrolimus metabolism. Within 24 h, tacrolimus trough levels fell daily at a significant level (p < 0.05) and all failed organs recovered their normal function within 48–72 h. Therefore, phenytoin metabolic induction appears to be a safe therapeutic option for patients with acute tacrolimus toxicity.

Keywords

• tacrolimus toxicity
• organ failure
• pharmacologic therapy
• cytochrome P450-3A
• phenytoin
• metabolic enhancement