Introduction 

Tacrolimus toxicity is a known complication in pediatric organ transplantation, though acute overdose is rare. Severe toxicity can cause seizures, encephalopathy, or posterior reversible encephalopathy syndrome (PRES). Management is supportive, as tacrolimus is protein-bound and not dialyzable. Phenytoin and fosphenytoin are CYP3A4 enzyme inducers, used in isolated cases to accelerate tacrolimus clearance. This case describes management of tacrolimus overdose using supportive care and fosphenytoin-induced enzyme induction. 

Method 

We present a case of a 2-year-old male, 17 months post-living donor liver transplant for biliary atresia, who ingested 30 mg of tacrolimus syrup (50-fold overdose from the prescribed 0.6 mg twice daily). Clinical presentation, laboratory findings, management, and outcomes were reviewed. 

Results 

The patient presented neurologically intact without tremor, seizures, or altered mental status. Initial evaluation revealed hyperkalemia (8.2 mEq/L) and peak tacrolimus level of 54.9 ng/mL at 12 hours post-ingestion. Hyperkalemia was corrected with calcium gluconate, insulin, and dextrose. Tacrolimus was held, and prophylactic levetiracetam was initiated. Intravenous fluid resuscitation resulted in a tacrolimus level decline from 54.9 to 17.1 ng/mL within 24 hours. Fosphenytoin was administered to induce CYP3A4 metabolism. After administration of fosphenytoin, tacrolimus levels declined from 17.2 ng/mL to 9.2 ng/mL. Renal function remained stable. He was discharged after 48 hours and maintained graft function. There was no evidence of acute kidney injury or graft rejection at follow-up. 

Conclusion 

This case demonstrates effective management of severe tacrolimus overdose using supportive care and fosphenytoin-induced enzyme induction, highlighting the importance of individualized, multidisciplinary collaboration when established protocols are lacking.