NO INCREASE IN CARBAMAZEPINE-10,11-EPOXIDE DURING ADDITION OF LAMOTRIGINE TREATMENT IN CHILDREN

It has been suggested that lamotrigine (LTG) may enhance the toxicity of carbamazepine (CBZ) by increasing the concentration of the active m etabolite carbamazepine-10,11-epoxide (CBZ-E) in adult patients. The a uthors investigated this hypothesis in an add-on study in 11 children and 3 adolescents, aged 6-22 years, who had been treated for more than 1 year with CBZ in monotherapy or with CBZ in combination with one or two other antiepileptic drugs. The LTG dosage was increased step by s tep until clinical response or side effects were observed. The plasma concentrations of LTG, CBZ, and CBZ-E were monitored during steady sta te conditions before and after the addition of LTG. It was found that LTG had no effect on mean CBZ concentrations and that it decreased rat her than increased the mean plasma concentration of CBZ-E from 6.4 +/- 2.6 to 4.9 +/- 2.4 mu mol/l (mean +/- SD, n = 14, P = 0.019). Observe d side effects were diplopia in two children, agitation in two, and in creased number of seizures in one. None of these five patients had unu sually high CBZ-E levels when the side effect developed. It is conclud ed that addition of lamotrigine in children treated with carbamazepine children does not result in a pharmacokinetic interaction with a toxi c accumulation of carbamazepine-10,11-epoxide.