1. Clinical Overview
Phenytoin is a first-generation hydantoin-derivative anticonvulsant, primarily used for the management of generalized tonic-clonic (grand mal) seizures and partial (focal) seizures. It is a non-sedative drug that stabilizes neuronal membranes by blocking voltage-gated sodium channels, thereby preventing the spread of seizure activity. It exhibits non-linear (Michaelis-Menten) pharmacokinetics, making therapeutic drug monitoring (TDM) crucial, especially in the Indian context where genetic polymorphisms in CYP2C9 and CYP2C19 can affect metabolism.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30 minutes to 2 hours; IV: Rapid, within minutes. | Variable, typically 12-24 hours due to long half-life at therapeutic doses. | Approximately 90% for oral formulations. |
2. Mechanism of Action
Phenytoin exerts its primary anticonvulsant effect by use-dependent blockade of voltage-gated sodium channels in neurons. It preferentially binds to and stabilizes the inactivated state of the channel, preventing high-frequency repetitive firing of action potentials. This inhibits the spread of seizure activity from epileptogenic foci without affecting normal neuronal conduction.
3. Indications & Uses
- Generalized tonic-clonic seizures (Grand mal epilepsy)
- Complex partial (focal) seizures
- Status epilepticus (using intravenous formulation)
- Prophylaxis and treatment of seizures following neurosurgery or traumatic brain injury
4. Dosage & Administration
Adult Dosage: Loading dose: 15-20 mg/kg IV (for status) or orally divided (e.g., 400-600 mg/day for 1-2 days). Maintenance: Start 100 mg TDS (300 mg/day). Usual range: 200-400 mg/day. MUST be individualized based on TDM.
Administration: Oral: Take with or after food to minimize GI upset. Swallow whole, do not crush or chew capsules. Suspension must be shaken vigorously. DO NOT switch between brands/formulations without monitoring. IV: For status epilepticus, infuse slowly (<50 mg/min in adults) with cardiac monitoring. Incompatible with many IV solutions; use only with normal saline.
5. Side Effects
Common side effects may include:
- Nystagmus (dose-related)
- Ataxia, dizziness, slurred speech
- Gingival hyperplasia (especially in children and young adults)
- Hirsutism
- Coarsening of facial features
- Gastrointestinal discomfort
- Mild cognitive impairment
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin | Phenytoin increases warfarin metabolism (decreased INR). Warfarin can displace phenytoin from protein binding. | Major |
| Carbamazepine | Mutual induction of metabolism, reducing levels of both drugs. | Major |
| Valproic Acid / Sodium Valproate | Valproate displaces phenytoin from protein binding (increases free fraction) and inhibits its metabolism. Complex interaction requiring free phenytoin level monitoring. | Major |
| Phenobarbital | Mutual enzyme induction, variable effect. | Moderate |
| Cimetidine, Omeprazole, Fluconazole | Inhibit phenytoin metabolism, increasing its levels. | Major |
| Rifampicin, Antiretroviral drugs | Induce phenytoin metabolism, decreasing its levels. | Major |
| Oral Contraceptives, Levonorgestrel | Phenytoin induces metabolism, reducing contraceptive efficacy. Advise alternative/barrier methods. | Major |
| Theophylline | Phenytoin decreases theophylline levels. | Moderate |
| Folic Acid | Folic acid may decrease phenytoin levels. | Moderate |
| Isoniazid (INH) | Potent inhibitor of phenytoin metabolism; high risk of toxicity. | Major |
7. Patient Counselling
- DO take the medicine at the same time(s) every day.
- DO NOT stop the medicine suddenly; this can cause withdrawal seizures.
- DO NOT change brands or switch between capsule and suspension without consulting your doctor.
- DO practice excellent oral hygiene (brush, floss, regular dental check-ups) to minimize gingival hyperplasia.
- DO inform all your doctors and dentists you are taking phenytoin.
- DO carry a seizure/medical ID card.
8. Toxicology & Storage
Overdose: Primarily CNS: Nystagmus, ataxia, slurred speech, lethargy progressing to coma. Cerebellar signs are prominent. At very high levels: Hypotension, bradycardia, cardiac arrest, respiratory depression. Death is usually from respiratory and circulatory depression.
Storage: Store at room temperature (15-30°C) in a dry place, protected from light. Keep the container tightly closed. Do not freeze. Keep out of reach of children. Suspension: Shake well before each use. Do not use if suspension is discolored or contains particles.