Drug Interactions Newsletter

Volume 1, Issue 2, 01/27/2009

Question

How does valproate (Depakene® or Depakote®) interact with lamotrigine (Lamictal®) to increase the risk of potentially life threatening skin rashes, such as Steven-Johnson Syndrome, when neither one of the drugs are known to be significant substrates or inhibitors of the CYP450 enzyme system?

Answer

This is one of many drug-drug interactions where clinicians cannot rely solely on knowing the cytochrome P450 enzyme system for predicting drug interactions. As it relates to this question, it is important to note that the coadministration of valproic acid and lamotrigine is possible given their FDA approved indications. Regardless of the formulation used (divalproex sodium (as 1:1 sodium valproate:valproic acid; Depakote®) or valproic acid only (Depakene®)), the active form in the body is valproate and is approved as monotherapy and adjunctive therapy in complex partial seizures and pediatric patients (≥ 10 years of age). Similarly, lamotrigine is indicated as adjunctive therapy for partial seizures, generalized seizures of Lennox-Gastaut syndrome, and primary generalized tonic-clonic seizures in adult and pediatric patients (≥2 years of age). It is also important to note that both are FDA approved for treatment of Bipolar I Disorder, thus highlighting the possibility of their coadministration.......To read the full answer please LOGIN or SUBSCRIBE NOW.