Abstracts

To determine the extent and clinically relevance of the pharmacokinetic interaction between oxcarbazepine (OXC) and lamotrigine (LTG). OXC and LTG are new antiepileptic drugs (AEDs) with increasing usage in clinical practice. It is a common belief that one of their advantages is the lack or at least minor degree of clinically relevant drug interactions caused by their application in combination therapies. However, in a small retrospective series the LTG level-to-dose-ratio (LDR) was 33% lower in combination with OXC (1) than with LTG alone. The most propable mechanism is an induction of LTG glucuronide conjugation enzymes which has already been described for an interaction between oral contraceptives and LTG (2)
Retrospective analysis of patients with combined use of OXC and LTG and OXC add-on or withdrawal to LTG treated at the Swiss Epilepsy Center since January 2002. Determination of serum levels (SLs) by high pressure liquid chromatography. Patients with single SLs as well as those with concomitant dosage changes of other AEDs like valproic acid (VPA) or enzyme inducers (AEDs and other drugs as well) with well-known effects on OXC and LTG SLs were excluded. Data from 18 patients (out of [gt] 100) remained for detailed analysis.
Add-on of OXC to LTG led to a significant fall of LTG SLs (mean: 34%, range 15[ndash]75%). OXC withdrawal was followed by rising OXC levels (up to more than 50%) leading to toxicity in some patients. On the other hand, a successful therapy with LTG and corresponding adequate SLs was possible in some other patients only after withdrawal of OXC. Illustrative case reports including the determination of glucuronidated LTG-metabolites in the urine in one patient will be presented.
OXC and LTG are new AEDs with a hitherto widely neglected new spectrum of possible pharmacokinetic interactions.
Clinicians have to be careful with a combined use of OXC and LTG especially when adding or withdrawing OXC in patients already treated with or remaining on LTG.
1) May TW, Rambeck B, Jürgens U. Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Therapeutic Drug Monitoring 1999; 21: 175-181
2) Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamtotrigine plasma levels reduced by oral contraceptives. Epilepsy Research 2001; 47: 151-154