Rapid resolution of tacrolimus intoxication-induced AKI with a corticosteroid and phenytoin

Ann Pharmacother. 2014 Nov;48(11):1525-8. doi: 10.1177/1060028014546184. Epub 2014 Aug 7.

Abstract

Objective: To report a novel approach to the management of tacrolimus intoxication that leads to rapid normalization of serum tacrolimus concentrations.

Case summary: 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.

Discussion: 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.

Keywords: clinical research; corticosteroids; drug interactions; immunosuppressants; poisoning.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Kidney Transplantation
  • Methylprednisolone / therapeutic use*
  • Phenytoin / therapeutic use*
  • Tacrolimus / adverse effects*

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Phenytoin
  • Tacrolimus
  • Methylprednisolone