Lamotrigine + Valproate interaction
Valproate (divalproex / valproic acid) doubles serum levels of lamotrigine by inHibiting UGT enzymes.
Also, valproate (VPA) may increase risk of lamotrigine-induced Stevens Johnson Syndrome (SJS) by a different mechanism. VPA can inhibit epoxide hydrolase enzymes and/or depletion of glutathione levels leading to SJS (Vazquez et al, 2018)
Most prescribers know about this interaction but tend to forget about it when adjusting lamotrigine dose. I have encountered several patients prescribed lamotrigine 300-400 mg concomitantly with VPA, which is a humungous dose.
Clinically significant pharmacokinetic interactions involving lamotrigine, and those involving VPA, are few. I have illustrated 7 for lamotrigine and 4 for VPA because these interactions are definitely worthy of memorization.
In addition to lamotrigine, there are other UGT1A4 substrates that may be potentially relevant, e.g., lumateperone (Caplyta)...but not relevant to include their picture mnemonics here.
UGT1A4 metabolizer genotype can be determined by pharmacogenetic testing, e.g., Genesight, Genomind, and IDgenetiX.
No one is UGT1A4 poor metabolizer, (PM) thankfully. If UGT1A4 PMs existed, they would have higher lamotrigine levels and be more likely to develop SJS.
When Cafer's Psychopharmacology Volume 2 is published, the Depakote DR Dipsies will be wearing doctors' coats. "When the doctor (DR) says Depakote (regular Depakote), she means Depakote DR (delayed release)".
Depakote ER (extended release) is another formulation of divalproex (2 VPA molecules bound together) that is 89% bioequivalent to Depakote DR, to make our lives complicated.
One other potentially relevant pharmacokinetic interaction with lamotrigine involves quetiapine (Seroquel), although a 30% decrease in quetiapine levels may not be noticeable.
