A 35-year-old woman with bipolar disorder and epilepsy is being started on lamotrigine. Her physician warns her about the risk of Stevens-Johnson syndrome and advises slower titration. This risk is significantly increased when lamotrigine is co-administered with which drug?
- A Carbamazepine
- B Phenytoin
- C Levetiracetam
- D Valproate ✓
Explanation
Valproate potently inhibits UGT enzymes (particularly UGT1A4 and UGT2B7) responsible for lamotrigine glucuronidation, increasing lamotrigine plasma levels by approximately 2-fold. This pharmacokinetic interaction dramatically increases the risk of lamotrigine-associated serious cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). When lamotrigine is added to valproate, the initial dose must be halved and the titration schedule doubled in duration. Carbamazepine and phenytoin are inducers that decrease lamotrigine levels.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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