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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.
* Carbamazepine is principally metabolized by CYP3A4 (also CYP2C8), but is also a potent inducer of CYP1A2, CYP3A4 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.
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* 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.
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* Carefully monitoring for clinical and laboratory evidence of altered effects is recommended, particularly when the dosage of either drug is changed. <ref name=”medicatiebewaking”> Schalekamp T. et al, Interacties met Psychofarmaca, Stichting Health Base, Houten, 2002. </ref> <ref name=”bazire”> Bazire S, Psychotropic Drug Directory 2007, HealthComm UK Limited, Aberdeen, 2007. </ref>
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