Major
Established
Descrição
Valproic acid doubles lamotrigine plasma concentrations by inhibiting its glucuronidation; the combination is associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.
Mecanismo
Valproic acid inhibits UGT1A4 and UGT2B7, the primary enzymes for lamotrigine glucuronidation, substantially reducing lamotrigine clearance and elevating systemic exposure.
Significância Clínica
The risk of life-threatening skin reactions (SJS/TEN) is significantly increased; the FDA mandates a slower lamotrigine titration schedule when co-prescribed with valproate.
Conduta
Use the specific lamotrigine titration schedule for valproate co-therapy (half the usual starting dose and titration rate); monitor skin closely.