Critical
Lamotrigine × Valproic acid
Antiepileptic with dual mechanism×Broad-spectrum antiepileptic, fatty acid derivative
Mechanism
Valproate inhibits UGT1A4 – the lamotrigine glucuronidation enzyme. Lamotrigine levels double. With rapid titration – fatal hypersensitivity with Stevens-Johnson syndrome and toxic epidermal necrolysis. Especially dangerous in children and adolescents.
Symptoms
Rash, fever, mucosal involvement within 2-8 weeks. Progression to SJS/TEN with 10-25% mortality.
Management
Start lamotrigine at 25 mg every other day for first 2 weeks (instead of 25 mg/day), increase by 25-50 mg every 2 weeks. Max dose 200 mg/day (instead of 400 mg). Stop immediately at rash onset.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.