Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review

Abstract

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.