Class
- Antiepileptic drug (AED)
Phenytoin
Commonly Prescribed for
(FDA approved in bold)
- Generalized tonic-clonic and complex partial seizures (monotherapy or adjunctive in adults and children)
- Treatment of seizures during or following neurosurgery
- Status epilepticus
- Trigeminal neuralgia
- Glossopharyngeal neuralgia
- Migraine prophylaxis
- Neuropathic pain
- Junctional epidermolysis bullosa
- Preeclampsia (alternative to magnesium sulfate)
- Cardiac arrhythmias (especially glycoside-induced)
- Myotonia
Phenytoin
How the Drug Works
- Reduces hyperexcitability, likely by effect on sodium channels
- May modulate T-type calcium channels, but not in the thalamus (unlike AEDs used for absence seizures)
Phenytoin
How Long Until It Works
- Seizures – may decrease by 2–3 weeks
- Trigeminal neuralgia – may start working in hours to weeks
Phenytoin
If It Works
- Seizures – goal is the remission of seizures. Continue as long as effective and well-tolerated. Consider tapering and slowly stopping after 2 years without seizures, depending on the type of epilepsy
- Pain – goal is the reduction of pain severity and frequency. If trigeminal neuralgia remits on medication, periodically attempt to lower dose or discontinue
Phenytoin
If It Doesn’t Work
- Increase to highest tolerated dose
- Epilepsy: consider changing to another agent, adding a second agent or referral for epilepsy surgery evaluation. Check drug level
- Pain – try an alternative agent
Phenytoin
Best Augmenting Combos for Partial Response or Treatment-Resistance
- Epilepsy: keep in mind drug interactions and their effect on levels
Phenytoin
Tests
- During intravenous administration, continuous heart monitoring is required, with frequent blood pressure checks
- Obtain blood counts monthly for the first few months due to risk of blood dyscrasias
Adverse Effects (AEs)
Phenytoin
How Drug Causes AEs
- CNS side effects are probably caused by sodium channel effects
Phenytoin
Notable AEs
- Nystagmus, ataxia, dysarthria, insomnia, nervousness, motor twitching, tremor, dizziness, impaired memory
- Gingival hyperplasia, rash (usually morbilliform), hirsutism, coarsening of facial features
- Pneumonia, sinusitis, rhinitis, asthma
- Tinnitus, diplopia, eye pain, taste loss
- Lymph node hyperplasia, chest pain, edema
- Soft tissue injury with intravenous use
Phenytoin
Life-Threatening or Dangerous AEs
- Hypotension, cardiac conduction abnormalities with rapid intravenous administration. Can be fatal. Less likely with phosphenytoin
- May inhibit insulin release and cause hyperglycemia. Rare diabetes insipidus
- Blood dyscrasias (thrombocytopenia or agranulocytosis)
- Rare serious allergic rash (Stevens-Johnson syndrome, lupus erythematosus syndrome)
- Rare lymphoma or multiple myeloma
- Toxic hepatitis and liver damage
- May cause cerebellar atrophy with long-term use at high doses
- “Purple glove syndrome” is a rare complication associated with intravenous use. Extremities become swollen, discolored, and painful. May require amputation
Phenytoin
Weight Gain
- Not Unusual
Phenytoin
Sedation
- Commom
Phenytoin
What to Do About AEs
- Side effects may decrease or remit after a longer time on a stable dose
- A small decrease in dose may improve side effects
- Stop drug for any hematologic abnormalities
- Recommend good oral hygiene to prevent gingival hyperplasia
Phenytoin
Best Augmenting Agents for AEs
- Take with food to avoid GI AEs
- Most AEs only improve with stopping drug or lowering dose
