Divalproex (valproate) and Felbamate interaction
Divalproex (valproate) and Felbamate: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
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
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.
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.
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.
Felbamate A study involving the co-administration of 1,200 mg/day of felbamate with valproate to patients with epilepsy (n=10) revealed an increase in mean valproate peak concentration by 35% (from 86 to 115 mcg/mL) compared to valproate alone.
Increasing the felbamate dose to 2,400 mg/day increased the mean valproate peak concentration to 133 mcg/mL (another 16% increase).
From the Felbamate (Felbatol) label · effective 2025-08-15
IT IS NOT KNOWN WHETHER CONCOMITANT USE OF OTHER ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECT THE INCIDENCE OF HEPATIC FAILURE.
Use in Conjunction with Other Antiepileptic Drugs (see DOSAGE AND ADMINISTRATION ) The addition of Felbatol ® to antiepileptic drugs (AEDs) affects the steady-state plasma concentrations of AEDs.
CBZ epoxide ↓ ↑ ↓ Phenobarbital ↑ ↓ Specific Effects of Felbatol® on Other Antiepileptic Drugs Phenytoin Felbatol ® causes an increase in steady-state phenytoin plasma concentrations.
Effects of Other Antiepileptic Drugs on Felbatol ® Phenytoin Phenytoin causes an approximate doubling of the clearance of Felbatol ® (felbamate) at steady-state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady-state trough concentrations of Felbatol ® as compared to the same dose of Felbatol ® given as monotherapy.
The net effect of these interactions is summarized in Table 2: Table 2 Steady-State Plasma Concentrations of Felbatol When Coadministered With Other AEDs AED Coadministered AED Concentration Felbatol ® Concentration Phenytoin ↑ ↓ Valproate ↑ ↔ No significant effect.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot 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.