Adding lamotrigine to valproic acid.
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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.
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- Lamotrigine is principally metabolised by UDP-glucuronosyltransferases.
- Lamotrigine generally has no significant effect on valproate levels, however caution is recommended.
- Start lamotrigine at low dose and check valproate plasma level after 1 week. Change valproate dose if necessary.  Very slow titration of lamotrigine is recommended, because lamotrigine-related skin rashes have been reported. 
- Valproic acid increases the blood level of lamotrigine because of the inhibition of glucuronidation. Adverse reactions, particularly skin rash, may occur with greater frequency or severity. Also other side effects may occur such as ataxia, tremor, sedation, and fatigue. However, such symptoms should improve as the dose of lamotrigine is decreased.
- Also important, when lamotrigine is added to valproate therapy, valproate concentrations may be possibly decreased.
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