Q: Which anti-epilectic drug can be use as an antidote in Tacrolimus Toxicity?

A) Phenytoin

B) Levetiracetam,

C) Carbamazepine

D) diazepam

E) Toprimate

Answer: A

Tacrolimus is metabolized by the CYP3A4 isoenzyme. Tacrolimus is subject to numerous drug-drug interactions. CYP3A4/PGP inhibitors may increase tacrolimus concentrations, whereas inducers may decrease tacrolimus concentrations. Phenytoin and Phenobarbital are commonly used antiepileptics and potent enzyme inducers. Another well known inducer is Rifampin.

No treatment recommendations exist for tacrolimus toxicity, as hemodialysis, plasma exchange, gastric lavage or activated charcoal are only minimally effective. Phenytoin and phenobarbital also have the additional benefit of seizure prevention as neurologic toxicities, including seizure and coma, are well documented with tacrolimus. 




References:

1. Arin S. Jantz, Samir J. Patel, Wadi N. Suki, Richard J. Knight, Arvind Bhimaraj, and A. Osama Gaber - Case Reports in Transplantation, Volume 2013 (2013)

2. R. E. Quirós-Tejeira, I. F. Chang, L. J. Bristow, S. J. Karpen, and J. A. Goss, “Treatment of acute tacrolimus whole-blood elevation with phenobarbital in the pediatric liver transplant recipient,” Pediatric Transplantation, vol. 9, no. 6, pp. 792–796, 2005.

3. G. E. McLaughlin, M. Rossique-Gonzalez, B. Gelman, and T. Kato, “Use of phenobarbital in the management of acute tacrolimus toxicity: a case report,” Transplantation Proceedings, vol. 32, no. 3, pp. 665–668, 2000.

4. 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.

5. K. 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.