Changes

* Valproic acid A synergistic effect is principally metabolized by CYP2C9, CYP2C19, CYP2A6 and UDP-glucuronosyltransferasessuggested.<ref''freeman''>{{Pubmed|9433333|Freeman et al. Valproic acid is an inhibitor Mood stabilizer Combinations: A Review of the enzymes CYP2C9, epoxide-hydroxylase Safety and UDPEfficacy. Am J Psychiatry 1998;155:12-glucuronosyltransferases.21}}</ref> 

* Define carbamazepine serum concentration (+ epoxide) before starting valproate. Check carbamazepine serum concentration (+ epoxide) again after 2 weeks and adapt dose if necessary. <ref name=”medicatiebewaking”> Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002. </ref> 

* Valproate can inhibit carbamazepine metabolic pathways, resulting in raised carbamazepine-epoxide concentrations. <ref> {{Pubmed|9241092|Bernus et al. The mechanism of the carbamazepine-valproate interaction in humans. Br J Clin Pharmacol 1997;44:21}}</ref>. 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.<ref''freeman''/>* 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.<ref''freeman''/>