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Combining-Lamotrigine-Valproic acid

Type moodstabilizer
Group anticonvulsant
ATC-code N03AX09
PubChem 3878
PubMed Lamotrigine lamotrigine
Kompas (Dutch) Lamotrigine
Wikipedia Lamotrigine
Valproic acid
Type moodstabilizer
Group anticonvulsant
ATC-code N03AG01
PubChem 3121
PubMed acid%22 Valproic acid valproic-acid
Kompas (Dutch) Valproic acid
Wikipedia Valproic acid

Adding valproic acid to lamotrigine.

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General information
  • 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.
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Start valproic acid
  • 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. [5] [6]
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  • Valproate can increase lamotrigine plasma levels significantly by inhibiting lamotrigine’s glucuronidation. This effect of valproate is dose-dependent.[7]
  • Very slow titration of lamotrigine is recommended because reports of lamotrigine-related skin rashes. [8]

  1. 1.0 1.1 Farmacotherapeutisch Kompas; Toxicologie (dutch)
  2. 2.0 2.1 Farmacotherapeutisch Kompas - lamotrigine (dutch) Cite error: Invalid <ref> tag; name "ftk" defined multiple times with different content
  3. lamotrigine
  4. KNMP; Informatorium Medicamentorum 2023; Monografie "valproaat" (Dutch)
  5. Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002.
  6. Pisani at al, Interaction of lamotrigine with sodium valproate. Lancet. 1993 May 8;341(8854):1224.
  7. Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007.
  8. 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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