1. Phenytoin Sodium & Fosphenytoin Sodium
2. Pharmacological Class: Hydantoin Antiepileptic (Class Ib Voltage-Gated Na+ Channel Blocker) • 3. Therapeutic Category: Neurology & Antiepileptic Medicines (Ch 11)
4. Clinical Overview & Verified Formulation Identity
Phenytoin Sodium & Fosphenytoin Sodium
Code: [11.13] | Stable ID: TIP-MED-000217
Eptoin (Abbott), Dilantin (Pfizer)
Oral Tablets / Capsules: 50 mg, 100 mg, 300 mg ER; Oral Suspension: 30 mg/5 mL, 125 mg/5 mL; IV Injection: 50 mg/mL (2 mL ampoule = 100 mg).; Oral Tablets / Capsules: 50 mg, 100 mg, 300 mg ER; Oral Suspension: 30 mg/5 mL, 125 mg/5 mL; IV Injection: 50 mg/mL (2 mL ampoule = 100 mg).
Route: Oral / Parenteral / Topical as specified by formulation
Schedule H (Drugs Rules, 1945 — High-Alert Narrow Therapeutic Index Drug)
True
5 & 6. Mechanism of Action & Pharmacodynamics
Stabilises neuronal membranes in the motor cortex by prolonging the voltage-dependent inactivation state of fast neuronal sodium channels (Nav), suppressing high-frequency repetitive action potential firing without causing general CNS depression.
8. Therapeutic Indications
- Generalised tonic-clonic seizures and focal (partial) seizures
- Status epilepticus (second-line IV loading after benzodiazepine administration) and post-neurosurgical seizure prophylaxis
10. Dosage and Administration (Educational Reference Summary)
Administration & Timing: Take consistently with food or milk to reduce gastric irritation; separate by >= 2 hours from antacids, calcium, iron, or nasogastric enteral feeds. IV infusion must NEVER exceed 50 mg/min in adults (25 mg/min in elderly) and must be diluted ONLY in 0.9% Normal Saline (precipitates in 5% Dextrose!).
11 & 13. Contraindications, Precautions and Warnings
- Sinus bradycardia, sinoatrial block, second- or third-degree AV block, or Adams-Stokes syndrome (IV formulation)
- Co-administration with Delavirdine or Rilpivirine (potent CYP3A4/P-gp induction causes virological failure)
- Absence (petit mal) or myoclonic seizures (may exacerbate seizures)
Saturable hepatic CYP2C9/2C19 metabolism: reduce maintenance dose in hepatic impairment and monitor rigorously for cerebellar toxicity (nystagmus, ataxia, dysarthria).
7, 12, 14–18. Detailed Pharmacokinetics, Interactions, Special Populations & Counselling
7 & 16. Pharmacokinetics (ADME) & Renal / Hepatic Considerations
7. Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion): Absorption, distribution, metabolism, and excretion follow class pharmacokinetic profile; verify patient renal/hepatic function.
16a. Renal Considerations: In severe renal impairment (CrCl < 25 mL/min) or hypoalbuminaemia (< 3.2 g/dL), plasma protein binding decreases and the free (active) phenytoin fraction increases; apply the Sheiner-Tozer albumin/uraemia correction equation or monitor free phenytoin levels.
16b. Hepatic Considerations: Saturable hepatic CYP2C9/2C19 metabolism: reduce maintenance dose in hepatic impairment and monitor rigorously for cerebellar toxicity (nystagmus, ataxia, dysarthria).
12 & 14. Adverse Effects & Drug Interactions
- Concentration-dependent CNS toxicity: Nystagmus (>20 mcg/mL), Ataxia (>30 mcg/mL), Dysarthria & Lethargy (>40 mcg/mL)
- Chronic effects: Gingival hyperplasia (20–40%), hirsutism, coarsening of facial features, Vitamin D deficiency osteomalacia, folate-deficiency megaloblastic anaemia
- Idiosyncratic: SJS/TEN (strongly associated with HLA-B*15:02 allele in South Asian populations) and DRESS syndrome; IV extravasation causes 'Purple Glove Syndrome'
- Potent CYP3A4/2C9/2C19 & UGT Inducer: Markedly reduces plasma efficacy of Oral Contraceptives, DOACs (Apixaban/Rivaroxaban), Warfarin, Carbamazepine, Lamotrigine, and Corticosteroids.
- CYP2C9/2C19 Inhibitors (Isoniazid, Fluconazole, Voriconazole, Amiodarone, Valproate): Precipitate acute Phenytoin toxicity due to saturated zero-order clearance.
- Enteral Tube Feeds & Calcium/Antacid Supplements: Chelate oral Phenytoin and reduce bioavailability by up to 70%; hold enteral feeds 2 hours before and 2 hours after oral Phenytoin suspension/tablets.
15, 17 & 18. Special Populations, Clinical Monitoring & Patient Counselling
15. Use in Special Populations (Pregnancy, Lactation, Paediatrics, Geriatrics): Evaluate maternal-foetal benefit-risk ratio, paediatric mg/kg ceiling, and geriatric renal function prior to prescribing.
17. Clinical & Laboratory Monitoring: Monitor clinical response, baseline renal/hepatic parameters, and relevant serum biomarkers.
18. Patient Counselling & Storage:- Never switch between different manufacturer brands or between Phenytoin Sodium (92% phenytoin acid) and Phenytoin Free Acid (100% phenytoin) without physician review and TDM.
- Report unsteady gait, slurred speech, double vision, or any new skin rash/mouth ulcers immediately.
- Maintain strict dental hygiene (soft toothbrush and flossing) to minimise gum overgrowth, and separate from calcium/antacids by at least 2 hours.
Storage & Dispensing Notes: Store tightly closed below 30°C protected from moisture. High-Alert NTI check: verify 100 mg tablet/capsule vs 30 mg paediatric tablet vs 25 mg/5 mL suspension.
Visual Pharmacology Illustration (PLATE-8.6)
19. Authoritative References & Source Traceability
Primary Reference Record: Indian Pharmacist Desk Reference — Professional Edition 2.7 (2026–27) by THE INDIAN PHARMACIST Editorial Reference; NFI 7th Ed (2026); Register D.8 p. 254.
Verification Portals: Indian Pharmacopoeia Commission (IPC) • CDSCO (India Jurisdiction) • NCBI Bookshelf • DailyMed (US FDA Label Reference)
Last Reviewed Date: 2026-11-08 • Related Study Guide: Epilepsy & Seizure Disorders ASM Guide →