Carbamazepine-1 0,11-epoxide Vomiting and ataxia

18 months after beginning therapy for adult onset epilepsy with phenytoin and phenobarbitone, a 55-year-old woman was admitted with confusion, unsteadiness and focal motor seizures_ Carbamazepine 600mg was added to the drug regimen and phenobarbitone withdrawn, and at the end of 3 months she was receiving phenytoin 350 mg/day and carbamazepine 1200 mg/day. Phenobarbitone was then reintroduced al 60 mg/day. Although her fits stopped and she regained consciousness, she was confused, dysphasic and increasingly ataxic, with associated vomiting. The serum carbamazepine concentrations were within the therapeutic range (33 lImol/L) but fluctuated considerably throughout the day. The serum carbamazepine-l0.11 -epoxide metabolite concentrations (13.5 /lmol/L) also fluctuated throughout the day and were higher in the mornings when symptoms were most severe.

When the carbamazepine dosage was reduced to 600 mg/day. serum carbamazep;ne-l D. l1-epoxide concentrations fell by 57-60% and the vomiting and ataxia resolved. However. serum carbamazepine levels remained constant. The authors conclude that the . - - . data clearly show a direct correlation between acute toxic side­effects and high total and free CBZ-E [carbamazepine-1 0, 11-epOxide] serum levels _ . -' and that ' ___ the routine monitoring of serum CBZ [carbamazepine] may not be a totally reliable indicator of Clinical toxicity in some patients, and that the routine monitoring of CBZ-E may also be necessary' . Pat.~alos. P.N. ; Stephenson T J : Krishna. S.: Elyas. A.A., Lascelles, P. T et al .. Lancet 2: 496 (31 Aug 1985)