Combining-Carbamazepine-Valproic acid

Carbamazepine
Type moodstabilizer
Group anticonvulsant
links
ATC-code N03AF01
Medscape Carbamazepine
PubChem 2554
PubMed Carbamazepine
Drugs.com carbamazepine
Kompas (Dutch) Carbamazepine
Wikipedia Carbamazepine
Valproic acid
Type moodstabilizer
Group anticonvulsant
links
ATC-code N03AG01
PubChem 3121
PubMed acid%22 Valproic acid
Drugs.com valproic-acid
Kompas (Dutch) Valproic acid
Wikipedia Valproic acid

Adding valproic acid to carbamazepine.

Infobord.png General information
  • Carbamazepine is principally metabolized by CYP3A4, and is a potent inducer of CYP1A2, CYP2C9, CYP3A4 and 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.
  • A synergistic effect is suggested.[5]
Eenrichtingbord.png Start valproic acid
  • Define carbamazepine serum concentration (+ epoxide) before starting valproate. Check carbamazepine serum concentration (+ epoxide) again after 2 weeks and adapt dose if necessary. [6]
Letopbord.png Cave
  • Valproate can inhibit carbamazepine metabolic pathways, resulting in raised carbamazepine-epoxide concentrations. [7] Valproate can also displace protein-bound carbamazepine and therefore increase the levels of free carbamazepine. This may result in neurotoxicity even when valproate levels are low.[5]
  • Carbamazepine induces metabolism of both itself and valproate via Cytochrome P450 3A3/4 system, which may decrease the serum concentrations of both drugs and increase the risk of relapse.[5]


  1. ↑ WHO Collaborating Centre for Drug Statistics Methodology ATC=N03AF01
  2. ↑ 2.02.1 Farmacotherapeutisch Kompas; Toxicologie (dutch)
  3. ↑ 3.03.1 Farmacotherapeutisch Kompas - carbamazepine (dutch) Cite error: Invalid <ref> tag; name "ftk" defined multiple times with different content
  4. ↑ 4.04.1 KNMP; Informatorium Medicamentorum 2015; Monografie "carbamazepine" (Dutch) Cite error: Invalid <ref> tag; name "informatorium" defined multiple times with different content
  5. ↑ 5.05.15.2 Freeman et al. Mood stabilizer Combinations: A Review of Safety and Efficacy. Am J Psychiatry 1998;155:12-21
  6. ↑ Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002.
  7. ↑ Bernus et al. The mechanism of the carbamazepine-valproate interaction in humans. Br J Clin Pharmacol 1997;44:21
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