Introduction
Dilantin (phenytoin) is an anticonvulsant medication that has been a cornerstone of epilepsy treatment since its FDA approval in 1953. As a hydantoin derivative, it remains one of the most widely prescribed antiepileptic drugs worldwide for controlling tonic-clonic and partial seizures.
Mechanism of Action
Phenytoin exerts its antiepileptic effects primarily by blocking voltage-gated sodium channels in neuronal membranes. It binds to the inactivated state of these channels, stabilizing them and preventing repetitive firing of action potentials. This use-dependent blockade reduces the spread of seizure activity from epileptogenic foci without significantly affecting normal neuronal conduction. Additionally, phenytoin may modulate calcium channels and inhibit glutamate release.
Indications
- Treatment of generalized tonic-clonic seizures
- Treatment of complex partial seizures (psychomotor, temporal lobe)
- Prevention and treatment of seizures occurring during or following neurosurgery
- Status epilepticus (IV formulation)
- Off-label: Certain cardiac arrhythmias (particularly those digitalis-induced) and neuropathic pain
Dosage and Administration
Oral Administration:- Adults: Initial dose 100 mg TID; maintenance dose 300-400 mg/day (may range 200-600 mg/day)
- Pediatrics: Initial dose 5 mg/kg/day in 2-3 divided doses; maintenance 4-8 mg/kg/day
- Status epilepticus: Loading dose 15-20 mg/kg at max rate 50 mg/min
- Maintenance: 100 mg every 6-8 hours
- Hepatic impairment: Reduce dose and monitor closely
- Renal impairment: Use with caution; consider free phenytoin levels
- Elderly: May require lower doses due to altered pharmacokinetics
Pharmacokinetics
Absorption: Variable and formulation-dependent; extended-release capsules have 90% bioavailability with slow absorption Distribution: Vd 0.6 L/kg; highly protein bound (90-95%); crosses placenta and blood-brain barrier Metabolism: Hepatic via cytochrome P450 enzymes (CYP2C9 and CYP2C19); saturable kinetics (zero-order at therapeutic levels) Elimination: Half-life 7-42 hours (dose-dependent); primarily renal excretion of metabolitesContraindications
- Hypersensitivity to phenytoin, other hydantoins, or components
- Sinus bradycardia, sinoatrial block, second- or third-degree AV block
- Adams-Stokes syndrome
- Concurrent delavirdine therapy
Warnings and Precautions
Boxed Warning: Risk of serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis- Cardiac effects: IV administration may cause hypotension, arrhythmias
- Hepatic injury: Monitor liver function periodically
- Hematologic effects: May cause megaloblastic anemia, leukopenia, thrombocytopenia
- Osteomalacia: Long-term use associated with decreased bone mineral density
- Suicidal ideation: Antiepileptic drugs may increase suicidal thoughts/behavior
- Withdrawal seizures: Abrupt discontinuation may precipitate status epilepticus
Drug Interactions
Metabolic Interactions:- CYP2C9/C19 inhibitors: Amiodarone, fluconazole, isoniazid (increase phenytoin levels)
- CYP2C9/C19 inducers: Rifampin, carbamazepine (decrease phenytoin levels)
- Valproic acid, aspirin, warfarin (increase free phenytoin fraction)
- Decreases levels of: oral contraceptives, warfarin, cyclosporine, theophylline, many antipsychotics
- Antacids: Reduce phenytoin absorption
- Dopamine: IV phenytoin may cause hypotension
- Fluoroquinolones: May alter phenytoin levels
Adverse Effects
Common (≥10%):- Nystagmus
- Ataxia
- Slurred speech
- Dizziness
- Gingival hyperplasia
- Coarse facial features
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Hepatic necrosis
- Agranulocytosis
- Aplastic anemia
- Cerebellar atrophy (with chronic use)
- Peripheral neuropathy
Monitoring Parameters
- Serum phenytoin levels: Therapeutic range 10-20 mcg/mL (total), 1-2 mcg/mL (free)
- CBC with platelets at baseline and periodically
- Liver function tests regularly
- Vitamin D and bone density monitoring with long-term use
- Signs of dermatologic reactions
- Neurologic examination for cerebellar signs
- Oral hygiene assessment for gingival hyperplasia
Patient Education
- Take consistently with regard to meals and formulation type
- Do not crush or chew extended-release capsules
- Maintain good oral hygiene to minimize gingival hyperplasia
- Avoid alcohol consumption
- Use effective contraception (phenytoin reduces efficacy of hormonal contraceptives)
- Report any skin rash, unusual bleeding, bruising, or infection immediately
- Do not stop abruptly; taper under medical supervision
- Be aware of potential cognitive effects (drowsiness, impaired coordination)
- Wear medical alert identification indicating epilepsy diagnosis and medication use
References
1. FDA Prescribing Information: Dilantin (phenytoin) 2. Glauser T, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness. Epilepsia 2013;54(3):551-63 3. Patsalos PN, et al. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring. Therapeutic Drug Monitoring 2008;30(1):1-13 4. Brodie MJ, et al. Epilepsy in adults. The Lancet 2019;393(10172):689-701 5. Anderson GD. Pharmacokinetics of antiepileptic drugs. In: Wyllie E, ed. The Treatment of Epilepsy. 6th ed. Lippincott Williams & Wilkins; 2015 6. Zaccara G, et al. Adverse effects of antiepileptic drugs. Acta Neurol Scand 2011;124(s191):30-5
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.