title: Rapid resolution of tacrolimus intoxication-induced AKI with a corticosteroid and phenytoin.
abstract: OBJECTIVE
  To report a novel approach to the management of tacrolimus intoxication that leads to rapid normalization of serum tacrolimus concentrations.
  
  
  METHODS
  A 9-year-old female renal transplant recipient developed a severe tacrolimus intoxication as a result of prolonged diarrhea, which resulted in acute kidney injury, severe dehydration, and neurological symptoms. We used a combination of intravenous steroids and intravenous phenytoin to normalize the tacrolimus level from 32 to 5 ng/mL in less than 24 hours, with complete resolution of symptoms and signs.
  
  
  CONCLUSIONS
  Tacrolimus intoxication is a rare event but may result in life-threatening complications. Treatment recommendations beyond holding the drug and enzyme induction with phenytoin or phenobarbital are elusive. This approach leads to a relatively slow normalization of the tacrolimus level over 72 hours. The authors hypothesized that additional induction of the p-glycoprotein through steroids was synergistic.
  
  
  CONCLUSIONS
  The combination of phenytoin and a corticosteroid may be an effective approach that leads to rapid normalization of severely elevated tacrolimus levels.
authors.affiliation: University of Western Ontario, Department of Paediatrics, London, ON, Canada Children's Hospital, London Health Sciences Centre, London, ON, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bax
authors.affiliation: University of Western Ontario, Department of Paediatrics, London, ON, Canada Children's Hospital, London Health Sciences Centre, London, ON, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Tijssen
authors.affiliation: University of Western Ontario, Department of Paediatrics, London, ON, Canada Children's Hospital, London Health Sciences Centre, London, ON, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rieder
authors.affiliation: University of Western Ontario, Department of Paediatrics, London, ON, Canada Children's Hospital, London Health Sciences Centre, London, ON, Canada guido.filler@lhsc.on.ca.
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
mesh_terms: D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D008775:Methylprednisolone / Q000627:therapeutic use*; D010672:Phenytoin / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects*
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D010672:Phenytoin; D016559:Tacrolimus; D008775:Methylprednisolone
keywords: clinical research; corticosteroids; drug interactions; immunosuppressants; poisoning