NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Updated July 13, 2026

Phenytoin

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

Phenytoin is one of the oldest and most widely used antiepileptic drugs, effective for partial seizures and generalized tonic-clonic seizures. It is also used for seizure prevention after neurosurgery and as a second-line agent for status epilepticus. Its nonlinear (zero-order) pharmacokinetics require careful dosing and monitoring.

Evidence tier
Strong
Indexed sources
10 1989–2022
Interactions
0
Depletes
5 nutrients
Read the sources → Compare profiles
Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

Phenytoin is one of the oldest and most widely used antiepileptic drugs, effective for partial seizures and generalized tonic-clonic seizures. NutriStack rates the supporting evidence as strong. Common adult dosing is 300-400 mg/day (extended-release) or 100 mg three times daily (immediate release); individualized by serum levels (as prescribed by your physician), though a prescriber sets the actual dose. With long-term use it can deplete folate, vitamin d, calcium. This profile indexes 10 sources.

What it's good for
  • Effective for tonic-clonic and focal seizures
  • IV formulation for status epilepticus2,3
  • Long clinical experience and well-characterized pharmacology9
  • Once-daily dosing with extended-release formulation
What to watch for
  • Gingival hyperplasia
  • Hirsutism and coarsening of facial features
  • Nystagmus and ataxia (dose-related)
  • Known hypersensitivity to phenytoin or other hydantoins1,2
  • Sinus bradycardia, SA block, second- or third-degree AV block, Adams-Stokes syndrome3

The bottom line

Evidence rating strong. Most-documented uses: effective for tonic-clonic and focal seizures, iv formulation for status epilepticus, long clinical experience and well-characterized pharmacology. 10 sources indexed (1989–2022), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Stabilizes neuronal membranes by blocking voltage-gated sodium channels in their inactivated state, reducing sustained repetitive firing. At therapeutic concentrations, it selectively inhibits the spread of seizure activity in the motor cortex without depressing normal neuronal signaling. Also modulates calcium channels and calmodulin-dependent processes.

Class
Antiepileptic
Absorption
Water-soluble; take with food
Dosing

Dosing & protocol.

Common range
300-400 mg/day (extended-release) or 100 mg three times daily (immediate release); individualized by serum levels (as prescribed by your physician)
Recommended form
Extended-release capsules (Dilantin Kapseals); IV fosphenytoin preferred for parenteral use

Highly protein-bound (~90%); many drug interactions due to CYP2C9/CYP2C19 metabolism and enzyme induction. Nonlinear pharmacokinetics mean small dose changes can produce large changes in serum levels.

Depletions

What it depletes.

Nutrients this medication can lower over time, and what to replace.

Folate

Significant

Phenytoin impairs intestinal folate absorption and increases folate catabolism during chronic use.

Replace MethylfolateMonitor Serum folate or RBC folateOnset Usually after months of therapy

Vitamin D

Significant

Hepatic enzyme induction accelerates vitamin D catabolism, lowering active vitamin D availability and worsening bone loss.

Replace Vitamin D3Monitor 25-OH vitamin DOnset Usually after months of therapy

Calcium

Significant

Reduced vitamin D activity and chronic anticonvulsant use lower calcium balance and bone mineral density.

Replace CalciumMonitor Serum calcium or bone density trendOnset Usually after months of therapy

Vitamin K

Moderate

Enzyme induction may lower vitamin K-dependent clotting factor support and vitamin K status in susceptible long-term users.

Replace Vitamin K2Monitor Undercarboxylated osteocalcin or clinical assessmentOnset Usually over months

Biotin

Moderate

Chronic anticonvulsant therapy can lower biotin status through increased metabolic turnover.

Replace Vitamin B7Monitor Clinical assessmentOnset Usually over months

Full Phenytoin depletion and interaction guide →

Safety

Full safety detail.

Side effects

  • Gingival hyperplasia
  • Hirsutism and coarsening of facial features
  • Nystagmus and ataxia (dose-related)
  • Peripheral neuropathy (chronic use)
  • Megaloblastic anemia (folate interference)
  • Osteomalacia with long-term use
  • Rash (including rare SJS/TEN)
  • Cerebellar atrophy (chronic high levels)

Contraindications

  • Known hypersensitivity to phenytoin or other hydantoins1,2
  • Sinus bradycardia, SA block, second- or third-degree AV block, Adams-Stokes syndrome3
  • Concurrent use with delavirdine
  • Hepatic impairment (increased free drug levels)1,9
  • Porphyria
  • Pregnancy (category D; associated with fetal hydantoin syndrome)
Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Meta-analyses & systematic reviews

6

Reviews & position papers

1

Reference material

3
FAQ

Common questions.

Quick answers about Phenytoin, drawn from the data on this page.

What is Phenytoin?

Phenytoin is one of the oldest and most widely used antiepileptic drugs, effective for partial seizures and generalized tonic-clonic seizures. It is also used for seizure prevention after neurosurgery and as a second-line agent for status epilepticus. Its nonlinear (zero-order) pharmacokinetics require careful dosing and monitoring.

What is Phenytoin used for?

Commonly cited benefits of Phenytoin include: Effective for tonic-clonic and focal seizures; IV formulation for status epilepticus; Long clinical experience and well-characterized pharmacology; Once-daily dosing with extended-release formulation. NutriStack rates the overall evidence as strong.

What is a typical dose of Phenytoin?

A typical adult dose of Phenytoin is 300-400 mg/day (extended-release) or 100 mg three times daily (immediate release); individualized by serum levels (as prescribed by your physician). The commonly recommended form is Extended-release capsules (Dilantin Kapseals); IV fosphenytoin preferred for parenteral use. These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Phenytoin?

Reported side effects include gingival hyperplasia, hirsutism and coarsening of facial features, nystagmus and ataxia (dose-related), peripheral neuropathy (chronic use), megaloblastic anemia (folate interference), osteomalacia with long-term use. This is educational information; check with a healthcare professional before use.

How strong is the evidence for Phenytoin?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

Phenytoin in NutriStack.

Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.

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NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.