AED(% protein-bound) Kidney Liver Bone marrow Heart Comment
Hyponatremia   Leukopenia Anemia   Monitor cyclosporine level
300 mg q.o.d. for severe renal failure300 mg after ~4 hrs hemodialysis   Useful during engraftment    
T1/2 ~48 hrs during severe renal failureT1/2 ~12 hrs during hemodialysis T1/2 ~110 hrs during severe hepatic failure     Serious rashes:~3/1000 adults~1/100 children
Reduce dose during renal failure
Supplemental dose after hemodialysis
  Useful during engraftment    
(MHD is ~40%)
Hyponatremia Liver converts to active MHD
Not studied in severe failure
Avoid during engraftment   Both an inhibitor and inducer of CYP450
Monitor cyclosporine level
Sedating Sedating Useful during engraftment   Monitor cyclosporine level
Steroid metabolism altered
Use free phenytoin levels Use free phenytoin levels Avoid during engraftment Use free phenytoin levels Monitor cyclosporine level
Steroid metabolism altered
Clearance reduced ~50% in renal failure
Need to adjust dose during hemodialysis
      Kidney stone: ~1% incidence
Valproic acid
Useful during hemodialysis because little is removed Avoid during hepatic failure Avoid during engraftment
Thrombocytopenia at high concentrations
  Severe hepatotoxicity or pancreatitis are rare
Avoid in patients
Avoid in renal failure Not studied in hepatic failure Avoid during engraftment   A sulfonamide
Kidney stone: ~4% incidence

MHD = monohydroxy derivative (active metabolite); T1/2 = terminal half-life.

Adapted from: Cruz-Martinez E and Gilmore RL. Transplantation and seizures. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;75-82.
With permission from Elsevier (

Authored By: 
E Cruz-Martinez and RL Gilmore
Reviewed By: 
Steven C. Schachter MD
Monday, March 1, 2004