What the FDA labels say about taking them together
Phenobarbital and valproic acid
Valproic acid's FDA label of January 24, 2025 names phenobarbital in its drug interactions section; phenobarbital's label does not name valproic acid itself but warns about its class (Anti-seizure medicines). The valproic acid label: “DRUG INTERACTIONS Hepatic enzyme-inducing drugs can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance.”
Check it at the source: the phenobarbital FDA label on DailyMed (effective August 27, 2026); the valproic acid FDA label on DailyMed (effective January 24, 2025, PAI Holdings, LLC dba PAI Pharma).
What does the phenobarbital label say about valproic acid?
Phenobarbital's label does not name valproic acid itself; it warns about its class (Anti-seizure medicines):
Phenobarbital label, warnings and precautionsIf a rash occurs, the patient should be evaluated for signs and symptoms of Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions (5.6)]. Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including phenobarbital.
Phenobarbital label, warnings and precautionsAntiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in adolescents and adults.
Source: FDA drug label (Phenobarbital), Chartwell RX, LLC, effective August 27, 2026 (SPL set 74428144-fb24-40a5-a670-3b876e2d116c), via openFDA; the full label on DailyMed
What does the valproic acid label say about phenobarbital?
Valproic acid label, drug interactionsDRUG INTERACTIONS 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.
Source: FDA drug label (VALPROIC ACID), PAI Holdings, LLC dba PAI Pharma, effective January 24, 2025 (SPL set 7d5cb52e-37dd-4dfa-a6f4-09f9548846c6), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Phenobarbital | Valproic acid | |
|---|---|---|
| Labeled for | Seizures and epilepsy | Seizures and epilepsy, Migraine |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.213 per tablet 100 mg tablet | $0.243 per capsule 250 mg capsule |
| Shortage now | A presentation being discontinued | Listed; available |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once