Divalproex (valproate) and Phenytoin interaction

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease.

In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, Depakote ER should only be used after other anticonvulsants have failed.

Co-administration of valproate (400 mg TID) with phenytoin (250 mg) in normal volunteers (n=7) was associated with a 60% increase in the free fraction of phenytoin.

Total plasma clearance and apparent volume of distribution of phenytoin increased 30% in the presence of valproate.

Both the clearance and apparent volume of distribution of free phenytoin were reduced by 25%.

Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin.

…defects), and abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy.