Phenytoin

# Phenytoin ## Overview - **Classification**: Hydantoin anticonvulsant. Class Ib antiarrhythmic. - **Mechanism**: Blocks voltage-gated sodium channels, stabilizing neuronal membranes and preventing repetitive neuronal firing. ## Primary Indications 1. **Generalized Tonic-Clonic Seizures**: Management of grand mal epilepsy. 2. **Complex Partial Seizures**: Treatment of psychomotor seizures. 3. **Status Epilepticus**: Treatment and prevention of seizures after neurosurgery. 4. **Digoxin-induced Arrhythmias**: For specific ventricular arrhythmias (less common use). ## Adult Dosing ### Standard Dosing **Generalized Tonic-Clonic / Complex Partial Seizures (Oral)** - **Loading Dose**: **10-15 mg/kg** orally, divided into 2-3 doses 2-4 hours apart. - **Maintenance Dose**: **300-600 mg/day** - **Frequency**: Once daily (extended release) or **100 mg** TID (prompt release). - **Route**: Oral **Status Epilepticus (IV Loading)** - **Dose**: **15-20 mg/kg** (Phenytoin sodium equivalent) - **Frequency**: Single dose - **Route**: IV (slow infusion, max **50 mg/min**) - **Special Considerations**: Requires cardiac monitoring. Infuse in 0.9% NaCl only. **Status Epilepticus (IV Maintenance)** - **Dose**: **4-8 mg/kg/day** - **Frequency**: Divided doses (e.g., **100 mg** every 6-8 hours) - **Route**: IV (slow infusion, max **50 mg/min**) ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment for total phenytoin. Monitor free phenytoin levels due to altered protein binding. - **Hepatic Impairment**: Reduce starting dose (e.g., **25-50% reduction**). Monitor free phenytoin levels closely. - **Elderly Patients**: Start with lower doses due to decreased metabolism and increased sensitivity. Monitor serum levels. ## Pediatric Dosing ### Neonates (0-28 days) - **Loading Dose**: **15-20 mg/kg** IV - **Maintenance Dose**: **5 mg/kg/day** IV/Oral - **Frequency**: Maintenance divided **BID** - **Maximum**: IV infusion rate max **1-3 mg/kg/min** (not exceeding **25 mg/min** overall). - **Special Notes**: Monitor free phenytoin levels due to altered protein binding. ### Infants (1-12 months) - **Loading Dose**: **15-20 mg/kg** IV/Oral - **Maintenance Dose**: **5-8 mg/kg/day** IV/Oral - **Frequency**: Maintenance divided **BID** or **TID** - **Maximum**: Maintenance can go up to **10 mg/kg/day** in some cases; monitor levels. ### Children (1-12 years) - **Loading Dose**: **15-20 mg/kg** IV/Oral - **Maintenance Dose**: **5-10 mg/kg/day** IV/Oral - **Frequency**: Maintenance divided **BID** or **TID** - **Maximum**: Oral maintenance max typically **300-400 mg/day**. IV infusion max **50 mg/min**. ### Adolescents (13-18 years) - **Dose**: Generally approach adult dosing. - **Maintenance Dose**: **300 mg/day** orally initially. - **Maximum**: Adult maximum doses apply (oral up to **600 mg/day**, IV **1500 mg/day**). ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to phenytoin or other hydantoins. - **Absolute**: Sinus bradycardia, SA block, 2nd/3rd degree AV block (IV administration). - **Absolute**: Stokes-Adams syndrome (IV administration). ### Common Adverse Effects - **Very Common (>10%)**: Nystagmus, ataxia, slurred speech, gingival hyperplasia, hirsutism, constipation. - **Common (1-10%)**: Dizziness, insomnia, headache, nausea, vomiting, rash (maculopapular). - **Serious but Rare**: Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), DRESS syndrome, aplastic anemia, hepatotoxicity, purple glove syndrome (IV extravasation). ### Key Drug Interactions - **CYP2C9/2C19 Substrate/Inducer**: Potent inducer of CYP enzymes. Can decrease efficacy of **warfarin**, **oral contraceptives**, **corticosteroids**, **digoxin**. - **Antiepileptics**: Levels affected by **carbamazepine**, **valproic acid**, **phenobarbital** (monitor levels). - **Folic Acid**: Phenytoin can cause folate deficiency; consider supplementation. - **Enteral Tube Feeds**: Decreased oral absorption; hold tube feeds 1-2 hours before/after or increase dose. ## Monitoring & Follow-up - **Before Treatment**: Baseline CBC with differential, LFTs, renal function, skin exam. - **During Treatment**: Serum total phenytoin levels (**10-20 mcg/mL**), free phenytoin levels (**1-2 mcg/mL**). - **During Treatment**: CBC and LFTs (initially weekly, then every 3-6 months). - **Clinical Signs**: Watch for nystagmus, ataxia, sedation, gingival overgrowth, rash, fever, lymphadenopathy. ## Clinical Pearls - 💡 **Tip 1**: Administer IV phenytoin slowly (max **50 mg/min** in adults) to prevent hypotension and cardiac arrhythmias. - 💡 **Tip 2**: IV phenytoin must be infused in **0.9% Normal Saline** only, as dextrose solutions cause precipitation. - 💡 **Tip 3**: Oral absorption is saturable; small dose increases can lead to disproportionately large serum level increases and toxicity. - 💡 **Tip 4**: Always consider free phenytoin levels in patients with hypoalbuminemia, renal/hepatic dysfunction, or significant drug interactions. - 💡 **Tip 5**: Good oral hygiene and regular dental check-ups are essential to minimize gingival hyperplasia. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.