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Abstract: PO2226

Psychosis as a Neurotoxic Manifestation of Extended-Release Tacrolimus

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical


  • Lyons, Shannon, Parkview Medical Center, Pueblo, Colorado, United States
  • Harberts, Scott W., Parkview Medical Center, Pueblo, Colorado, United States
  • Wiseman, Alexander C., University of Colorado, Denver, Colorado, United States
  • Sicher, Stanley Carlos, Parkview Medical Center, Pueblo, Colorado, United States

Tacrolimus is a calcineurin inhibitor used in renal transplant to reduce the risk of rejection. Common side effects include infection, nephrotoxicity, and neurotoxicity (7). The neurotoxic effects can manifest as psychosis, paranoia, and bi-polar mania (4, 2). The unpredictable nature of tacrolimus pharmacokinetics has led to the development of extended-release tacrolimus such as Envarsus XR (8, 9, 12). While data is lacking, Envarsus XR is thought to have a lower incidence of neurotoxic side-effects (10, 1, 11). To our knowledge, there are no recorded cases in the literature of psychosis related to Envarsus XR (3,6). We present a case of acute paranoia secondary to Envarsus XR.

Case Description

Ms. H is a 62 year old woman who underwent allogenic renal transplant and was placed on immediate-release tacrolimus 0.5 mg twice daily. Due to high tacrolimus levels (average 9.6 ng/dl) she was switched to Envarsus XR 0.75 mg daily and subsequently reported new onset emotional disturbance. She was initially treated with fluoxetine then switched to citalopram without relief. She then developed paranoid ideation and refused to sleep. The patient and family felt this behavior correlated with starting Envarsus XR. This was discussed with her transplant team and Envarsus XR was continued as her tacrolimus levels were within goal (average 5.3 ng/dl). Her paranoia worsened and she was seen by psychiatry and placed on risperidone 2 mg daily. She continued to experience paranoid delusions and behavioral disturbance. She was then switched from Envarsus XR back to immediate-release tacrolimus and had complete resolution of symptoms. Her current average tacrolimus level is 5.05 ng/dl.


This case presents a unique instance of extended-release tacrolimus induced psychosis. While immediate-release tacrolimus is well known to cause neurotoxicity (5, 13), extended release is generally felt to be safer (12, 9). This case illustrates that while extended-release Tacrolimus formulations may have a reduced incidence of neurological side effects, they are not devoid of them. The SIMPLE trial is currently ongoing and its data may shed more light on tacrolimus induced neurotoxicity (10). Regardless of the outcome of this research, the treatment for tacrolimus induced neurotoxicity should always be to decrease the dose or withdraw the medication (14).