Adding valproic acid to lamotrigine.
- Lamotrigine is principally metabolised by UDP-glucuronosyltransferases.
- Valproic acid is principally metabolized by CYP2C9, CYP2C19, CYP2A6 and UDP-glucuronosyltransferases. Valproic acid is an inhibitor of the enzymes CYP2C9, epoxide-hydroxylase and UDP-glucuronosyltransferases.
- This combination of drugs may have possible synergistic effects. However, the pharmacokinetic drug interactions will influence the plasma levels. Dose adaptation will be recommended for this combination.
- Reduce the lamotrigine dose by 50% of the general dose when combined with valproate. Start valproate at low dose and increase dose based on serum concentration slowly.  
- Valproate can increase lamotrigine plasma levels significantly by inhibiting lamotrigine’s glucuronidation. This effect of valproate is dose-dependent.
- Very slow titration of lamotrigine is recommended because reports of lamotrigine-related skin rashes. 
- Farmacotherapeutisch Kompas; Toxicologie (dutch)
- Farmacotherapeutisch Kompas - lamotrigine (dutch)
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- Drugs.com lamotrigine
- KNMP; Informatorium Medicamentorum 2015; Monografie "valproaat" (Dutch)
- Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002.
- Pisani at al, Interaction of lamotrigine with sodium valproate. Lancet. 1993 May 8;341(8854):1224.
- Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007.
- Chang CC at al, Toxic epidermal necrolysis with combination lamotrigine and valproate in bipolar disorder. Prog Neuropsych. Biol Psychiatry. 2006 Jan;30(1):147-50
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