Adding valproic acid to topiramate.
- Topiramate induces CYP3A4 and is an inhibitor of CYP2C19.
- 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.
- Start valproic acid according to the general dosing advice.
- Pharmacologic response to the drugs should be monitored more closely following addition or withdrawal of one or the other drug. Dose adjustments may be required if an interaction is suspected.
- Topiramate plasma levels are increased by about 15% by valproate, which could be important if valproate is withdrawn. 
- Farmacotherapeutisch Kompas - topiramaat (dutch)
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- Farmacotherapeutisch Kompas; Toxicologie (dutch)
- KNMP; Informatorium Medicamentorum 2015; Monografie "valproaat" (Dutch)
- Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007.
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