Combining-Valproic acid-Carbamazepine
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Adding carbamazepine to valproic acid.
General information- 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.
- Carbamazepine is principally metabolized by CYP3A4, and is a potent inducer of CYP1A2, CYP2C9, CYP3A4 and UDP-glucuronosyltransferases.
- A synergistic effect is suggested.[5]
Start carbamazepine- Valproate can increase carbamazepine-epoxide serum concentrations. Define valproate serum concentration before starting carbamazepine.
- Start carbamazepine according to the general dosing advice. Check valproate and carbamazepine serum concentration (+ epoxide) after 2 weeks of therapy and adapt dose if necessary. [6]
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]
- ↑ 1.0 1.1 Farmacotherapeutisch Kompas; Toxicologie (dutch)
- ↑ 2.0 2.1 Farmacotherapeutisch Kompas - valproinezuur (dutch)
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<ref>tag; name "ftk" defined multiple times with different content - ↑ 3.0 3.1 KNMP; Informatorium Medicamentorum 2023; Monografie "valproaat" (Dutch)
Cite error: Invalid
<ref>tag; name "informatorium" defined multiple times with different content - ↑ WHO Collaborating Centre for Drug Statistics Methodology ATC=N03AF01
- ↑ 5.0 5.1 5.2 Freeman et al. Mood stabilizer Combinations: A Review of Safety and Efficacy. Am J Psychiatry 1998;155:12-21
- ↑ Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002.
- ↑ Bernus et al. The mechanism of the carbamazepine-valproate interaction in humans. Br J Clin Pharmacol 1997;44:21
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