Using Valproic Acid and Lamotrigine

lamotrigine (LTG)in combination with valproic acid (VPA) may work synergistically to provide superior seizure control than each drug independently
VPA inhibits LTG metabolism by UGT1A4 glucuronidation, increasing plasma LTG concentrations^[1]
Valproic acid (VPA) decreases lamotrigine (LTG) clearance by 30% at 125 mg/day and 50% at 250 mg and higher^[2]
maximal inhibition of LTG clearance by VPA occurs at doses of 500 mg/day
when converting from VPA plus LTG therapy to LTG monotherapy: LTG may be kept steady until VPA is dropped to 125 mg/day, then raised by 30% and doubled on VPA discontinuation
when converting from LTG monotherapy to a polytherapy regimen with VPA, the dose of LTG can be cut by 50% (without affecting stable LTG concentrations) on the day that VPA is started at doses of 250mg/day or higher
when LTG is added to VPA, the risk of rash may increase unless LTG is introduced at a low dose and tapered up slowly but adding VPA per se to an LTG regimen does not increase this risk because the patient has already taken LTG long enough to become desensitised to this effect^[3]

1. ^a Milosheska D, Lorber B, Vovk T, Kastelic M, Dolžan V, Grabnar I. Pharmacokinetics of lamotrigine and its metabolite N-2-glucuronide: Influence of polymorphism of UDP-glucuronosyltransferases and drug transporters. Br J Clin Pharmacol. 2016 Aug;82(2):399-411. doi: 10.1111/bcp.12984. Epub 2016 May 29.
[PMID: 27096250] [PMCID: 4972156] [DOI: 10.1111/bcp.12984]

2. ^a Gidal BE, Sheth R, Parnell J, Maloney K, Sale M. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy Res. 2003 Dec;57(2-3):85-93. doi: 10.1016/j.eplepsyres.2003.09.008.
[PMID: 15013050] [DOI: 10.1016/j.eplepsyres.2003.09.008]

3. ^a Kanner AM. When thinking of lamotrigine and valproic acid, think "pharmacokinetically"!. Epilepsy Curr. 2004 Sep-Oct;4(5):206-7. doi: 10.1111/j.1535-7597.2004.04515.x.
[PMID: 16059503] [PMCID: 1176375] [DOI: 10.1111/j.1535-7597.2004.04515.x]