Dilantin (phenytoin) is a cornerstone anticonvulsant medication with a long-standing history in neurological therapeutics. As a hydantoin derivative, it functions primarily by stabilizing neuronal membranes and limiting the spread of seizure activity, making it a first-line and adjunctive treatment for various seizure types. Its well-characterized pharmacokinetic profile allows for predictable dosing in appropriate patient populations, though therapeutic drug monitoring is essential. This product card provides a comprehensive overview for healthcare professionals to ensure its safe and effective clinical application.

Features

• Active Pharmaceutical Ingredient: Phenytoin sodium
• Available Formulations: Extended-release oral capsules (30 mg, 100 mg), chewable tablets (50 mg), oral suspension (125 mg/5 mL), and injectable solution (50 mg/mL)
• Mechanism of Action: Use-dependent blockade of voltage-gated sodium channels
• Therapeutic Class: Hydantoin anticonvulsant
• Bioavailability: Formulation-dependent; exhibits nonlinear (saturable) pharmacokinetics
• Half-life: Dose-dependent; typically 22 hours for a 300 mg daily dose (range 7-42 hours)
• Protein Binding: Approximately 90% bound to plasma proteins, primarily albumin
• Metabolism: Hepatic, primarily via CYP2C9 and CYP2C19

Benefits

• Provides effective control and prevention of generalized tonic-clonic seizures and partial (focal) seizures.
• Offers a rapid onset of action when administered via intravenous loading for status epilepticus.
• Features multiple administration routes (PO, IV) for flexibility in both acute and chronic management.
• Has a well-established efficacy and safety profile backed by decades of clinical use and research.
• Once-daily dosing is possible with the extended-release formulation in stabilized patients, improving adherence.
• Serves as a critical therapeutic option for patients refractory to other anticonvulsant medications.

Common use

Dilantin is indicated for the control of generalized tonic-clonic (grand mal) seizures, complex partial (psychomotor, temporal lobe) seizures, and for the prevention and treatment of seizures occurring during or following neurosurgery. It is not effective for absence (petit mal) seizures. The intravenous formulation is a primary agent for the emergent treatment of status epilepticus.

Dosage and direction

Dosing is highly individualized and must be titrated based on clinical response and serum concentration monitoring to achieve a therapeutic range, typically 10-20 mcg/mL.

• Adults: Oral loading dose: 1 gram divided into 3 doses (400 mg, 300 mg, 300 mg) at 2-hour intervals. Maintenance: Initiate at 100 mg TID or a single daily dose of extended-release capsules (300 mg). Adjust in 30-100 mg increments at 7-10 day intervals.
• Pediatrics: Oral loading dose: 15-20 mg/kg. Maintenance: Initiate at 5 mg/kg/day in 2-3 divided doses. Not to exceed 300 mg daily. Adjust based on levels and response.
• Status Epilepticus (IV): Loading dose: 15-20 mg/kg at a rate not exceeding 50 mg per minute.
• Administration: Administer with food to minimize GI upset. Do not substitute between brands, formulations, or between phenytoin and fosphenytoin arbitrarily due to bioavailability differences. Shake oral suspension well. The IV formulation must be administered in a large vein with a saline flush to avoid serious local toxicity (Purple Glove Syndrome).

Precautions

• Therapeutic Drug Monitoring (TDM): Mandatory due to nonlinear pharmacokinetics. Monitor serum concentrations, especially following dose adjustments, with changes in product formulation, and when adding or discontinuing interacting drugs.
• Hepatic Impairment: Use with extreme caution; reduced protein binding and impaired metabolism can lead to toxicity. Monitor free (unbound) phenytoin levels in patients with hypoalbuminemia (e.g., cirrhosis, nephrotic syndrome, elderly).
• Withdrawal: Abrupt discontinuation may precipitate status epilepticus. Taper gradually.
• Endocrine: May lower serum levels of T4 and T3; increased TSH levels have been reported. Monitor patients on thyroid medication.
• Hematologic: Cases of agranulocytosis, thrombocytopenia, and leukopenia have been reported. Perform baseline and periodic blood counts.
• Pregnancy: Category D. There is positive evidence of human fetal risk. Use only if the potential benefit justifies the potential risk to the fetus (risk of major congenital malformations, including cleft lip/palate and cardiac defects).

Contraindications

• Hypersensitivity to phenytoin, other hydantoins, or any component of the formulation.
• Patients with a history of prior phenytoin-induced hepatotoxicity.
• Sinus bradycardia, sinoatrial block, second- and third-degree AV block, and Adams-Stokes syndrome.
• Coadministration with delavirdine (phenytoin may lead to loss of virologic response and possible resistance to delavirdine or to the entire class of non-nucleoside reverse transcriptase inhibitors).

Possible side effect

Adverse reactions are often dose-related and correlate with serum concentrations.

• Common (>10%): Nystagmus, ataxia, slurred speech, decreased coordination, dizziness, drowsiness, gingival hyperplasia, constipation.
• Less Common (1-10%): Nausea, vomiting, headache, tremor, insomnia, transient nervousness, morbilliform rash.
• Rare but Serious (<1%): Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), hepatic necrosis, lupus erythematosus, lymphadenopathy, blood dyscrasias (agranulocytosis, pancytopenia, leukopenia), peripheral neuropathy, osteomalacia (due to altered vitamin D metabolism).

Drug interaction

Dilantin is a potent inducer of hepatic enzymes (CYP3A4, CYP2C9, CYP2C19, UGT) and is itself a substrate of CYP2C9 and CYP2C19. This creates a high potential for complex interactions.

• Drugs that INCREASE phenytoin levels: Amiodarone, chloramphenicol, chlordiazepoxide, cimetidine, disulfiram, estrogens, fluconazole, isoniazid, omeprazole, phenothiazines, salicylates, sertraline, sulfonamides, ticlopidine, tolbutamide, warfarin.
• Drugs that DECREASE phenytoin levels: Carbamazepine, chronic alcohol abuse, reserpine, rifampin, theophylline.
• Drugs whose levels are DECREASED by phenytoin: Oral anticoagulants (e.g., warfarin), corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, theophylline, vitamin D, many antiretrovirals, and numerous chemotherapeutic agents.
• Other Notable Interactions: Concomitant use with valproic acid increases free (unbound) phenytoin levels and decreases total levels. Concomitant use with lamotrigine may decrease lamotrigine levels.

Missed dose

If a dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped. Do not double the next dose to “catch up,” as this can precipitate toxicity due to the drug’s nonlinear kinetics.

Overdose

Signs and Symptoms: Toxicity is primarily neurological and includes nystagmus, ataxia, dysarthria, lethargy, slurred speech, nausea, vomiting. Severe overdose can lead to coma, hypotension, and respiratory depression. Death is rare. Management: Provide supportive care, including securing the airway and ensuring adequate ventilation. Hemodynamic support may be necessary. Gastric lavage may be considered if ingestion was recent. Multiple-dose activated charcoal may enhance elimination. Hemodialysis is not effective due to high protein binding. Serum level monitoring is crucial to guide management.

Storage

Store at room temperature (20°C to 25°C or 68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). Protect from light and moisture. Do not freeze the oral suspension. The injectable solution may form a precipitate at low temperatures, which should dissolve upon reaching room temperature with minimal shaking. If precipitate remains, discard the vial.

Disclaimer

This information is intended for educational and informational purposes for healthcare professionals only and is not a substitute for professional medical advice, diagnosis, or treatment. The prescribing physician is responsible for determining the appropriate dosage and monitoring therapy for each individual patient, considering their complete medical history, concomitant medications, and clinical status. Always consult official prescribing information and relevant clinical guidelines before initiating treatment.

Reviews

“Dilantin remains a workhorse in our epilepsy clinic. Its efficacy in controlling focal to bilateral tonic-clonic seizures is undeniable. The necessity for vigilant TDM and awareness of its complex interaction profile is a challenge, but one that is manageable with careful practice.” – Neurologist, 15 years experience

“While newer agents have emerged, Dilantin’s rapid IV efficacy in status epilepticus and its low cost keep it essential in both hospital and resource-limited settings. We constantly educate on the signs of serious rash and the importance of not missing doses.” – Clinical Pharmacist, Hospital Setting

“The gingival hyperplasia can be a significant issue for long-term pediatric patients, requiring diligent dental care. However, for many, it provides seizure freedom that other medications could not achieve.” – Pediatric Neurologist