Phenytoin and Absence Seizures
Phenytoin is known to worsen absence seizures and should be avoided in patients with this seizure type. 1
Phenytoin's Clinical Indications
Effective Seizure Types
Phenytoin demonstrates efficacy for:
- Generalized tonic-clonic seizures – Phenytoin is considered a treatment of choice for generalized major motor seizures 2
- Partial (focal) seizures – Effective for simple partial, complex partial, and secondarily generalized tonic-clonic seizures 3, 4
- Status epilepticus – Used as a second-line agent after benzodiazepines, with 84% efficacy but carries a 12% hypotension risk 5, 1
Ineffective or Contraindicated Seizure Types
Phenytoin worsens absence seizures and should never be used for primary generalized epilepsies that include absence or myoclonic components. 1 This represents a critical prescribing error that can lead to increased seizure frequency and patient harm.
Formulation Availability
Phenytoin is available in multiple dosage forms to accommodate different clinical scenarios:
- Intravenous formulation – Standard dose 18 mg/kg at maximum 50 mg/min for acute seizure management 1
- Oral capsules and suspension – For maintenance therapy, typically 200-700 mg/day 1
- Fosphenytoin (prodrug) – Can be administered more rapidly (150 mg/min) with fewer infusion site reactions than phenytoin 1, 6
These formulations allow treatment across pediatric and adult populations, though the drug's adverse effect profile limits its use as a first-line agent in many patients 3.
Critical Safety Considerations
Neurological Adverse Effects
Phenytoin causes dose-related CNS toxicity including:
- Nystagmus, ataxia, slurred speech, and mental confusion 7
- Phenytoin encephalopathy – Manifesting as cognitive impairment and cerebellar syndrome, particularly concerning in patients with intellectual disability 3
- Peripheral polyneuropathy with long-term use 7
Cardiovascular Risks
Intravenous phenytoin requires continuous ECG and blood pressure monitoring due to a 12% risk of hypotension – significantly higher than valproate (0% hypotension risk). 5, 8 Fatal hemodynamic complications have been reported with IV administration 6.
Other Serious Adverse Effects
- Severe dermatological reactions – Including Stevens-Johnson syndrome and toxic epidermal necrolysis 7
- Hematologic complications – Thrombocytopenia, leukopenia, agranulocytosis (some fatal) 7
- Gingival hyperplasia – A characteristic adverse effect not seen with newer agents 7
- Increased morbidity and mortality when used for seizure prophylaxis 1
Clinical Positioning
Phenytoin is not recommended as first-choice therapy for epileptic seizures except as a co-drug for managing convulsive status epilepticus. 3 Newer agents such as levetiracetam (68-73% efficacy, minimal cardiovascular effects) and valproate (88% efficacy, 0% hypotension) offer superior safety profiles for most indications. 5
In patients with intellectual disability, balance disturbances, or cognitive dysfunction, replacement of phenytoin with carbamazepine or oxcarbazepine is recommended. 3 Long-term phenytoin use should be avoided in patients with marked cognitive impairment or cerebellar disease. 3