Antiseizure medications · Neurology
Phenytoin
Dilantin®(brand names vary by market)
The drug where dose and concentration stop being proportional.
Also: oral liquid, injection
Mechanism
Blocks voltage-gated sodium channels in their inactivated state, slowing recovery and limiting high-frequency firing.
Indications
- Focal and generalised tonic-clonic seizures
- Status epilepticus
Formulations
Dosing concepts
Zero-order kinetics
Metabolism saturates within the therapeutic range. Below saturation a dose increase raises the level proportionally; above it, a small increase can double the level. Dose changes are therefore small and followed by a check.
Albumin correction
The assay measures total drug and about 90 percent is protein-bound. In hypoalbuminaemia or uraemia the free fraction rises, so a 'low' total level can be a therapeutic or toxic free level. Correcting for albumin is not optional.
Intravenous rate
Rapid infusion causes hypotension and arrhythmia from the propylene glycol diluent, which is why a maximum rate exists and fosphenytoin was developed.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- High but formulation-dependent
- Half-life
- Dose-dependent; roughly 22 h at therapeutic levels and much longer above them
- Elimination
- hepatic: CYP2C9 and CYP2C19, and a potent inducer of CYP3A4 and others: it lowers the levels of a long list of drugs
- Protein binding
- ~90%
Adverse effects
- Nystagmus, ataxia, slurred speechcommonThe classic toxicity ladder, appearing in that order as the level climbs.
- Gingival hyperplasiacommon
- Hirsutism and coarsening of facial featurescommon
- Rash, including Stevens-Johnson syndromeseriousHLA-B*1502 carries much of the risk in some populations.
- Purple glove syndrome after intravenous useserious
- Osteomalacia and folate deficiency with long-term useserious
Contraindications & precautions
Contraindications
- Sinus bradycardia or high-grade AV block (intravenous)
- Prior hypersensitivity
Precautions
- Hypoalbuminaemia
- Hepatic impairment
- Pregnancy
- Any drug whose level it will induce downward
Interactions
Monitoring
Level, corrected for albumin
The whole point of the drug's difficulty · After any dose change, and whenever toxicity is suspected
Clinical signs before the level
Nystagmus appears before the number is reported
Full blood count, liver enzymes, and rash
Idiosyncratic reactions
Levels of everything else it induces
It lowers warfarin, DOACs, contraceptives and much else
Counselling points
- Take it exactly as prescribed and do not change brands without telling us.
- See a dentist regularly and brush carefully; gum overgrowth is preventable with good hygiene.
- Report any rash immediately.
- It interferes with the contraceptive pill and many other medicines: always mention it.
Clinical pearls
- A patient with a 'low' phenytoin level and unmistakable ataxia is usually hypoalbuminaemic. Treating the number rather than the patient makes them worse.
- As an enzyme inducer it silently lowers the effect of oral contraceptives, direct oral anticoagulants and many others; the interaction is by omission, so nothing looks wrong until a pregnancy or a clot.
References & review
- Phenytoin product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.