Major
Established
Mô tả
Valproic acid doubles lamotrigine plasma concentrations by inhibiting its glucuronidation; the combination is associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.
Cơ chế
Valproic acid inhibits UGT1A4 and UGT2B7, the primary enzymes for lamotrigine glucuronidation, substantially reducing lamotrigine clearance and elevating systemic exposure.
Ý nghĩa lâm sàng
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.
Xử trí
Use the specific lamotrigine titration schedule for valproate co-therapy (half the usual starting dose and titration rate); monitor skin closely.