Divalproex (valproate) and Phenobarbital, hyoscyamine, atropine, and scopolamine interaction

Divalproex (valproate) and Phenobarbital, hyoscyamine, atropine, and scopolamine: the Divalproex (valproate) prescribing label describes an interaction that usually calls for monitoring, a dose change, or spacing the doses.

Moderate

Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.

What the FDA labels say

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

Moderate

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance.

Drug interactionsnames Phenobarbital, hyoscyamine, atropine, and scopolamineView label on DailyMed
Moderate

Co-administration of valproate (250 mg BID for 14 days) with phenobarbital to normal subjects (n=6) resulted in a 50% increase in half-life and a 30% decrease in plasma clearance of phenobarbital (60 mg single-dose).

Drug interactionsnames Phenobarbital, hyoscyamine, atropine, and scopolamineView label on DailyMed
Moderate

The fraction of phenobarbital dose excreted unchanged increased by 50% in presence of valproate.

Drug interactionsnames Phenobarbital, hyoscyamine, atropine, and scopolamineView label on DailyMed
Moderate

All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity.

Drug interactionsby drug classView label on DailyMed
Moderate

Serum barbiturate concentrations should be obtained, if possible, and the barbiturate dosage decreased, if appropriate.

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.