Divalproex (valproate) and Rufinamide interaction

Divalproex (valproate) and Rufinamide: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Divalproex (valproate) (Depakote ER) label · effective 2026-03-31

Major

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease.

Boxed warningby drug classView label on DailyMed
Major

In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, Depakote ER should only be used after other anticonvulsants have failed.

Boxed warningby drug classView label on DailyMed
Moderate

Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose ( 7.2 )

Drug interactionsnames RufinamideView label on DailyMed
Moderate

Rufinamide Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate.

Drug interactionsnames RufinamideView label on DailyMed
Moderate

Rufinamide concentrations were increased by <16% to 70%, dependent on concentration of valproate (with the larger increases being seen in pediatric patients at high doses or concentrations of valproate).

Drug interactionsnames RufinamideView label on DailyMed

From the Rufinamide (Banzel) label · effective 2022-12-15

Moderate

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase…

Drug interactionsby drug classView label on DailyMed
Moderate

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6).

Drug interactionsby drug classView label on DailyMed
Minor

If abrupt discontinuation of the drug is medically necessary, the transition to another AED should be made under close medical supervision.

Warnings and precautionsby drug classView label on DailyMed
Minor

Effects of BANZEL on other AEDs Population pharmacokinetic analysis of average concentration at steady state of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, and valproate showed that typical rufinamide C avss levels had little effect on the pharmacokinetics of other AEDs.

Drug interactionsby drug classView label on DailyMed
Minor

Table 6 summarizes the drug-drug interactions of BANZEL with other AEDs.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.