A 26-year-old woman with bipolar disorder is started on lamotrigine alongside her existing valproate. Two weeks later she reports a spreading rash with mucosal involvement. Which statement best explains the interaction?
- A Lamotrigine displaces valproate from protein binding, causing valproate toxicity
- B Valproate induces CYP450 metabolism, lowering lamotrigine levels and prompting dose escalation
- C Valproate inhibits glucuronidation of lamotrigine, nearly doubling its levels and increasing Stevens-Johnson syndrome risk ✓
- D The combination causes additive bone marrow suppression independent of lamotrigine levels
Correct answer: C. Valproate inhibits glucuronidation of lamotrigine, nearly doubling its levels and increasing Stevens-Johnson syndrome risk
Explanation
Lamotrigine is cleared mainly by glucuronidation. Valproate inhibits this pathway, roughly doubling lamotrigine concentrations, so the recommended lamotrigine dose is halved and titration slowed when the two are combined. This raises the risk of serious rash including Stevens-Johnson syndrome, which mandates stopping the drug if mucosal involvement appears. Enzyme inducers like carbamazepine have the opposite effect, which is why option B is wrong.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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