Pharmacology · Antiseizure medicines
Phenytoin !
An old, inexpensive sodium channel blocker for seizures. Its levels rise steeply with small dose changes, and long use can enlarge the gums.
Updated 2026-11-01
Also called: Diphenylhydantoin
Mechanism of action
Phenytoin blocks voltage-gated sodium channels in a voltage-dependent way, slowing their recovery from inactivation. This stops the sustained high-frequency discharges of a seizure focus while leaving normal, slower firing mostly intact.
- Binds sodium channels during repeated depolarization
- Slows the channel's recovery from inactivation
- Sustained high-frequency firing stops
- The seizure does not spread
Pharmacokinetics
- Absorption
- Absorbed by mouth; enteral feeding preparations can lower levels
- Distribution
- Highly bound to albumin; in low albumin or kidney failure the free level is the useful one
- Metabolism
- In the liver by CYP2C9 and CYP2C19; metabolism saturates, so small dose increases can raise levels a lot (non-linear kinetics)
- Half-life
- On average about 14 hours with chewable tablets (range about 7 to 29 hours), longer at high levels
Indications
- Focal seizures and generalized tonic-clonic seizures Epilepsy and seizures →
- Prevention and treatment of seizures during or after neurosurgery
- Status epilepticus (intravenous phenytoin or its prodrug fosphenytoin) Epilepsy and seizures →
Adverse effects
Common
- Nystagmus, unsteadiness (ataxia), slurred speech and drowsiness, which rise with the level
- Gingival hyperplasia
- Coarsening of facial features and excess hair
- Rash
Contraindications
- Hypersensitivity to phenytoin or other hydantoins
- Previous liver injury caused by phenytoin
- Use with delavirdine
Key interactions
- Valproate and other highly protein-bound drugs
- Displace phenytoin and change the free level
- CYP2C9 or CYP2C19 inhibitors
- Phenytoin levels rise quickly because metabolism is saturable
- Hormonal contraceptives, anticoagulants and many other drugs
- Phenytoin induces their metabolism and lowers their levels
- Enteral feeding
- Lower phenytoin levels
What is monitored
- Serum phenytoin level, free level if albumin is low
- Signs of toxicity: nystagmus, ataxia, confusion
- Complete blood count and liver tests
- Gum health and bone health in long use
Administration and safety
- Oral forms (capsules, chewable tablets, suspension) are not interchangeable without care
- Phenytoin dissolves poorly in water, which limits its intravenous use; the water-soluble prodrug fosphenytoin was developed for parenteral use
- Withdrawn gradually: stopping suddenly can trigger status epilepticus
Nursing care
- Check levels and look for nystagmus, unsteadiness or confusion
- Teach careful oral hygiene and regular dental visits
- Teach to report rash, fever or swollen glands
- Separate from enteral feeds as the protocol says and watch levels
Pregnancy and breastfeeding
Linked to malformations such as oral clefts and heart defects and to the fetal hydantoin syndrome; benefits and risks are weighed with specialist care.
Test yourself
Think of the answer, then tap the question to see it.
Why can a small dose increase of phenytoin cause toxicity?
Its liver metabolism saturates at therapeutic levels, so kinetics become non-linear and levels rise much more than the dose.
Which cosmetic adverse effect is typical of long-term phenytoin?
Gingival hyperplasia; coarsening of facial features and excess hair also occur.
Which early neurological sign suggests rising phenytoin levels?
Nystagmus, followed by unsteadiness (ataxia), slurred speech and confusion.
Why is the free phenytoin level preferred in a patient with low albumin?
Phenytoin is highly bound to albumin; with low albumin the free, active fraction is higher than the total level suggests.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Phenytoin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - PHENYTOIN tablet, chewable (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 20 (McGraw Hill, 2023); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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