Mesuximide Valproate

Phenobarbital, phenytoin, and possibly felbamate increase the levels of the active metabolite of mesuximide, IV-desmethylmesux-imide. Mesuximide increases the serum levels of phenobarbital and phenytoin, and decreases the levels of lamotrigine, and to a lesser extent, valproate. 

A retrospective analysis of serum valproate levels was carried out in 17 patients who started and/or stopped taking mesuximide and whose concurrent medication remained unaltered. In the 14 patients starting mesuximide, a mean decrease in valproate levels of 32% was seen. In the 8... 

It has been suggested that phenobarbital, phenytoin and felbamate compete with mesuximide for the same metabolic mechanisms (hydroxyla-tion) in the liver. As a result each one is metabolised more slowly and therefore their levels increase. Mesuximide appears to increase the clearance of valproate, and lamotrigine (which is principally via glucuronida-tion). 

Information about these interactions is limited. Nevertheless, concurrent use should be monitored. Anticipate the need to reduce the dose of phenytoin, phenobarbital or primidone if mesuximide is given. The dose of lamotrigine may need to be increased if mesuximide is given. There is also some evidence that the dose of valproate may need to be increased. 

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