Q: Which of the following may be use as an antidote in Tacrolimus toxicity?

A)  Eslicarbazepine acetate (Aptiom)
B)  Gabapentin (Neurontin)
C)  Phenytoin (Dilantin)
D)  Levetiracetam (Keppra)
E) Divalproex (Depakote) 


Answer: C

 Tacrolimus is metabolized by the CYP3A enzymes, which are found in the liver and intestinal wall. Unfortunately, hemodialysis or plasma exchange are ineffective in Tacrolimus toxicity. It has been suggested that CYP3A4 inducers phenytoin and phenobarbital can used to increase the clearance and of the tacrolimus. They also have the additional benefit of seizure prevention, another well documented effect of tacrolimus overdose. 


References:

1. Z. Karasu, A. Gurakar, J. Carlson et al., “Acute tacrolimus overdose and treatment with phenytoin in liver transplant recipients,” Journal of Oklahoma State Medical Association, vol. 94, no. 4, pp. 121–123, 2001.

2. Wada, M. Takada, T. Ueda et al., “Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 case reports,” International Journal of Clinical Pharmacology and Therapeutics, vol. 45, no. 9, pp. 524–528, 2007