Two medicines, side by side
Phenytoin vs valproic acid
Phenytoin and valproic acid are both labeled for seizures and epilepsy. Drugs@FDA records approvals of phenytoin since 1953 and of valproic acid since 1978. Pharmacies paid $0.145 per phenytoin sod ext 100 mg capsule and $0.243 per valproic acid 250 mg capsule (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. In FDA's classes, phenytoin is an anti-epileptic agent and valproic acid a mood stabilizer.
Check it at the source: the phenytoin FDA label on DailyMed (effective October 15, 2024); the valproic acid FDA label on DailyMed (effective January 24, 2025).
Highlights of the phenytoin record
Phenytoin (Dilantin) · label of October 15, 2024
Used for
From the label: indicationsPHENYTEK ® capsules (extended phenytoin sodium capsules) are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. […]
On the market
- Earliest approval on file
- January 6, 1953
- Generic labelers
- 29 labelers
- Pharmacy cost
- $0.145 per capsule
Supply and safety
- Shortage
- No current entry
- Recalls
- 11
Highlights of the valproic acid record
Valproic acid (Depakene) · label of January 24, 2025
LIFE THREATENING ADVERSE REACTIONS WARNING: LIFE THREATENING ADVERSE REACTIONS See full prescribing information for complete boxed warning. Hepatotoxicity, including fatalities, usually during the first 6 months of treatment. Children under the age of two years and patients with mitochondrial disorders are at higher risk.
Used for
From the label: indicationsValproic acid is indicated for: Monotherapy and adjunctive therapy of complex partial seizures; sole and adjunctive therapy of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 1.1 Epilepsy Valproic acid is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. […]
On the market
- Earliest approval on file
- February 28, 1978
- Generic labelers
- 22 labelers
- Pharmacy cost
- $0.243 per capsule
Supply and safety
- Shortage
- Listed; available
- Recalls
- 2
Source: FDA drug labels via openFDA (Phenytoin label of October 15, 2024, Valproic acid label of January 24, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do phenytoin and valproic acid differ on the record?
In FDA's classes, phenytoin is an anti-epileptic agent and valproic acid a mood stabilizer.
How each works, in its label's words: Phenytoin, “The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a …”; Valproic acid, “Valproic acid dissociates to the valproate ion in the gastrointestinal tract.”
Half-life, in each label's words: Phenytoin, “Elimination The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to …”; Valproic acid, “Mean terminal half-life for valproate monotherapy ranged from 9 to 16 hours following oral dosing regimens of 250 to …”
Only the valproic acid label carries a boxed warning.
Generics: phenytoin since 1975; valproic acid since 1986 (Drugs@FDA).
| Phenytoin | Valproic acid | |
|---|---|---|
| Labeled for | Seizures and epilepsy | Seizures and epilepsy, Migraine |
| Pharmacologic class | Anti-epileptic Agent | Anti-epileptic Agent, Mood Stabilizer |
| How it works (label) | The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency … | Valproic acid dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established. |
| Half-life (label) | Elimination The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours. | Mean terminal half-life for valproate monotherapy ranged from 9 to 16 hours following oral dosing regimens of 250 to 1,000 mg. |
| Earliest approval on file (Drugs@FDA) | January 6, 1953 | February 28, 1978 |
| First generic approved | July 16, 1975 | February 28, 1986 |
| Generic labelers (NDC) | 29 labelers | 22 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.145 per capsule (Phenytoin sod ext 100 mg capsule) | $0.243 per capsule (Valproic acid 250 mg capsule) |
| 12-month price change | -5% | -4% |
| Boxed warning | No | Yes |
| Shortage now | No current entry | Listed; available |
| Recalls recorded | 11 | 2 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 40,278 | 51,380 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
Do their labels mention each other?
Phenytoin label, drug interactionsInteracting Agent: Antiepileptic drugs; Examples: Phenobarbital, valproate sodium Valproate sodium and valproic acid are similar medications. The term valproate has been used to represent these medications., valproic acid
Valproic acid label, warnings and precautions… other antiepileptic drug monotherapy treatments evaluated: lamotrigine (108 [95% C.I. 105-110]), carbamazepine (105 [95% C.I. 102-108]), and phenytoin (108 [95% C.I. 104-112]).
Source: FDA drug labels via openFDA
What next?
- Alternatives to phenytoin
- every medicine labeled for the same conditions