Fenitoin

# Fenitoin ## Overview - **Classification**: Anticonvulsant, Hydantoin derivative - **Mechanism**: Stabilizes neuronal membranes by prolonging the inactivation of voltage-gated sodium channels, reducing neuronal excitability and preventing seizure propagation. ## Primary Indications 1. **Tonic-clonic (Grand Mal) Seizures** - Treatment and prevention 2. **Complex Partial (Psychomotor) Seizures** - Treatment and prevention 3. **Status Epilepticus** - IV formulation for rapid control 4. **Neuro-surgical Seizure Prophylaxis** - Prevention of seizures following head trauma or surgery ## Adult Dosing ### Standard Dosing **Status Epilepticus (IV Loading)** - **Dose**: **15-20 mg/kg** (Phenytoin equivalent) - **Frequency**: Single dose - **Route**: IV infusion, rate **≤50 mg/min** - **Maximum Dose**: **1500 mg** per dose - **Special Considerations**: Monitor ECG and BP during infusion. May require further loading (5-10 mg/kg) if seizures persist. **Maintenance Seizure Control (Oral/IV)** - **Dose**: **100 mg** - **Frequency**: Three times daily (**TID**) - **Route**: Oral or IV - **Alternative**: **300 mg** extended-release capsule once daily (**QD**) - **Target Level**: Adjust to achieve therapeutic levels (**10-20 mcg/mL** total, **1-2 mcg/mL** free). **Neuro-surgical Seizure Prophylaxis (Oral/IV Loading)** - **Loading Dose**: **10-20 mg/kg** PO/IV (divided for oral over 3 doses, 2-4 hr apart) - **Maintenance Dose**: **100 mg** TID PO/IV ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment but monitor free phenytoin levels due to altered protein binding. - **Hepatic Impairment**: Start with lower doses (**e.g., 25% reduction**); closely monitor free phenytoin levels due to reduced metabolism. - **Elderly Patients**: Start at lower doses and titrate slowly due to decreased metabolism, increased sensitivity, and potential for polypharmacy. ## Pediatric Dosing ### Neonates (0-28 days) - **Loading Dose (Status Epilepticus)**: **15-20 mg/kg** IV - **Frequency**: Single dose - **Maximum**: **500 mg** - **Special Notes**: Infuse at **≤1-3 mg/kg/min**. - **Maintenance Dose**: **5 mg/kg/day** divided - **Frequency**: Every 8-12 hours (**BID-TID**) - **Maximum**: Up to **10 mg/kg/day** - **Special Notes**: Highly variable PK; close Therapeutic Drug Monitoring (TDM) is essential. ### Infants (1-12 months) - **Loading Dose (Status Epilepticus)**: **15-20 mg/kg** IV - **Frequency**: Single dose - **Maximum**: **1000 mg** - **Special Notes**: Infuse at **≤1-3 mg/kg/min** or **≤50 mg/min**, whichever is slower. - **Maintenance Dose**: **5 mg/kg/day** divided - **Frequency**: Every 8-12 hours (**BID-TID**) - **Maximum**: Up to **10 mg/kg/day** ### Children (1-12 years) - **Loading Dose (Status Epilepticus)**: **15-20 mg/kg** IV - **Frequency**: Single dose - **Maximum**: **1500 mg** - **Special Notes**: Infuse at **≤50 mg/min**. - **Maintenance Dose**: **5-10 mg/kg/day** divided - **Frequency**: Every 8-12 hours (**BID-TID**) - **Maximum**: Up to **300-600 mg/day** (or adult dose equivalent). - **Special Notes**: Children may require higher mg/kg doses due to faster metabolism. ### Adolescents (13-18 years) - **Loading Dose (Status Epilepticus)**: **15-20 mg/kg** IV - **Frequency**: Single dose - **Maximum**: **1500 mg** - **Maintenance Dose**: Transition to adult dosing, typically **300 mg/day** divided - **Frequency**: Every 8-12 hours (**BID-TID**) - **Maximum**: **600 mg/day** ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to phenytoin or other hydantoins. - **Absolute**: Sinus bradycardia, SA block, 2nd or 3rd degree AV block, Stokes-Adams syndrome (IV use). - **Absolute**: Co-administration with delavirdine. - **Relative**: History of phenytoin-induced rash. ### Common Adverse Effects - **Very Common (>10%)**: Nystagmus, ataxia, slurred speech, gingival hyperplasia, hirsutism, coarsening of facial features. - **Common (1-10%)**: Dizziness, confusion, headache, nausea, vomiting, constipation, rash, osteomalacia. - **Serious but Rare**: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), DRESS syndrome, severe hypotension/arrhythmias (IV), aplastic anemia, hepatic failure, pseudolymphoma, Purple Glove Syndrome (IV extravasation). ### Key Drug Interactions - **Amiodarone, Fluconazole, Isoniazid, Cimetidine**: Increase phenytoin levels by inhibiting metabolism; monitor for toxicity. - **Carbamazepine, Phenobarbital, Rifampin**: Decrease phenytoin levels by inducing metabolism; monitor for loss of seizure control. - **Warfarin**: Phenytoin can initially increase then decrease warfarin effect; monitor INR closely. - **Oral Contraceptives**: Phenytoin decreases efficacy; advise alternative contraception. - **Antacids, Sucralfate**: Decrease oral phenytoin absorption; separate administration by **2-3 hours**. - **Enteral Tube Feeds**: Decrease oral phenytoin absorption; hold feed **1-2 hours** before/after dose. ## Monitoring & Follow-up - **Before Treatment**: Complete Blood Count (CBC) with differential, Liver Function Tests (LFTs), renal function, baseline ECG (for IV use). - **During Treatment**: - **Therapeutic Drug Monitoring (TDM)**: Total phenytoin levels (**10-20 mcg/mL**), Free phenytoin levels (**1-2 mcg/mL**). - **Frequency**: Weekly after initiation/dose changes, then every few months once stable. - **LFTs**: Periodically. - **CBC**: Periodically. - **Calcium/Vitamin D**: Periodically due to osteomalacia risk. - **Gingival Exams**: Regularly for hyperplasia. - **Clinical Signs**: - **Toxicity**: Nystagmus (early sign), ataxia, slurred speech, confusion, sedation. - **Hypersensitivity**: Rash, fever, lymphadenopathy. - **IV Infusion**: Hypotension, bradycardia, arrhythmias. ## Clinical Pearls - 💡 **IV Administration**: Infuse IV phenytoin slowly (**≤50 mg/min** in adults) directly or via an in-line filter. Avoid dextrose solutions as it precipitates. - 💡 **Oral Formulations**: Extended-release capsules can be dosed once daily. Oral suspension must be shaken vigorously. Do not crush or chew extended-release capsules. - 💡 **Non-linear Kinetics**: Phenytoin exhibits zero-order (non-linear) kinetics at therapeutic concentrations. Small dose changes can lead to disproportionately large changes in drug levels, requiring careful titration. - 💡 **Protein Binding**: Phenytoin is highly protein-bound. In hypoalbuminemia, renal/hepatic impairment, or in neonates, monitor free phenytoin levels, as total levels may be misleading. - 💡 **Gingival Hyperplasia**: Emphasize excellent oral hygiene and regular dental check-ups to manage this common side effect. - 💡 **Purple Glove Syndrome**: A rare but serious complication of IV phenytoin extravasation; choose large veins and monitor injection site closely. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.