Adding valproic acid to carbamazepine.
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- Carbamazepine is principally metabolized by CYP3A4, and is a potent inducer of CYP1A2, CYP2C9, CYP3A4 and UDP-glucuronosyltransferases.
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- 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.
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. 
Stop valproic acid
- Valproate can inhibit carbamazepine metabolic pathways, resulting in raised carbamazepine-epoxide concentrations.  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.
- 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.
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