Dilantin (phenytoin) is a cornerstone antiepileptic drug (AED) with a long-standing history of proven efficacy in the management of seizure disorders. As a hydantoin derivative, it functions primarily by stabilizing neuronal membranes and decreasing seizure activity through use-dependent blockade of voltage-gated sodium channels. This product card provides a comprehensive, expert-level overview of its pharmacological profile, clinical application, and essential safety information for healthcare professionals managing patients with epilepsy and certain other neurological conditions. Its role is particularly significant in the treatment of tonic-clonic and partial seizures, offering a reliable option for long-term maintenance therapy.

Features

• Active Pharmaceutical Ingredient: Phenytoin sodium.
• Available Formulations: Chewable tablets, oral suspension, and injectable solution for intravenous or intramuscular administration.
• Mechanism of Action: Use-dependent blockade of voltage-gated sodium channels, prolonging the inactivated state and preventing high-frequency neuronal firing.
• Pharmacokinetics: Exhibits saturable (non-linear, Michaelis-Menten) metabolism, necessitating careful therapeutic drug monitoring (TDM).
• Bioavailability: Formulation-dependent; the oral suspension and chewable tablets are bioequivalent.
• Half-life: Dose-dependent, typically ranging from 7 to 42 hours.

Benefits

• Provides effective and reliable control of generalized tonic-clonic and complex partial (focal impaired awareness) seizures.
• Offers a well-established safety and efficacy profile supported by decades of clinical use and research.
• Available in multiple formulations (oral and parenteral) to accommodate various clinical scenarios, from chronic outpatient management to acute inpatient status epilepticus.
• Facilitates personalized medicine through therapeutic drug monitoring, allowing for dose individualization to achieve optimal serum concentrations.
• Serves as a first-line option for the prevention and treatment of seizures following neurosurgery or traumatic brain injury.

Common use

Dilantin is indicated for the control of generalized tonic-clonic (grand mal) seizures and complex partial (psychomotor, temporal lobe) seizures. It is not effective for absence (petit mal) seizures. It is also approved for the prevention and treatment of seizures occurring during or following neurosurgery. Its use is firmly established in both adult and pediatric populations, though dosing must be carefully adjusted based on age, weight, and metabolic capacity.

Dosage and direction

Dosing is highly individualized and must be guided by therapeutic drug monitoring, with a typical therapeutic range of 10-20 mcg/mL (total phenytoin).

• Adults: Initial dosage for patients not previously treated is often 100 mg orally three times daily (300 mg/day). Adjust dosage in 30-50 mg increments at appropriate intervals (e.g., every 7-10 days) based on clinical response and serum levels. Maintenance doses commonly range from 300 mg to 400 mg daily, though some patients may require up to 600 mg daily.
• Pediatrics: Initial dose of 5 mg/kg/day in 2-3 divided doses. Maintenance doses are typically 4-8 mg/kg/day. Dosing in children is particularly sensitive due to variable metabolic rates.
• Loading Dose: In urgent situations, a loading dose of 15-20 mg/kg IV (for status epilepticus) or orally (for rapid outpatient initiation) can be administered under close medical supervision.
• Administration: Oral suspension must be shaken vigorously immediately before each use. To minimize the risk of gingival hyperplasia, patients should maintain excellent oral hygiene. Administration with food can minimize gastric upset.

Precautions

• Therapeutic Drug Monitoring (TDM): Mandatory due to saturable metabolism. Small dosage increases can lead to disproportionate, large increases in serum concentration, resulting in toxicity.
• Hepatic Impairment: Use with extreme caution. Phenytoin is extensively metabolized by the liver. Reduced hepatic function can lead to significantly elevated levels and toxicity.
• Renal Impairment: Caution is advised. The pharmacokinetic profile may be altered, and uremia can decrease protein binding, increasing the free (active) fraction of the drug.
• Hypoalbuminemia: Conditions causing low serum albumin (e.g., malnutrition, nephrotic syndrome) increase the free fraction of phenytoin, potentiating its effect and toxicity. Dose adjustments and monitoring of free phenytoin levels are critical.
• Cardiac Effects: Intravenous administration must be performed cautiously at a rate not exceeding 50 mg per minute due to the risk of severe hypotension and cardiac arrhythmias.
• Endocrine: May alter glucose metabolism; diabetic patients should be monitored closely. Can also decrease serum concentrations of T4 and lead to increased serum levels of glucose, alkaline phosphatase, and gamma-glutamyl transferase (GGT).
• Hematologic: Rare but serious blood dyscrasias, including leukopenia, neutropenia, pancytopenia, and megaloblastic anemia, have been reported. Periodic blood counts are advisable.
• Pregnancy: Category D. There is positive evidence of human fetal risk. Use during pregnancy requires a careful risk-benefit analysis. Fetal Hydantoin Syndrome is a well-documented teratogenic risk.

Contraindications

Dilantin is contraindicated in patients with:

• A known hypersensitivity to phenytoin, other hydantoins, or any component of the formulation.
• Sinus bradycardia, sinoatrial block, second- and third-degree AV block, and Adams-Stokes syndrome.
• A history of prior acute hepatotoxicity attributable to phenytoin.

Possible side effect

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

• Common (CNS-related): Nystagmus, ataxia, slurred speech, dizziness, insomnia, transient nervousness, motor twitching, headache.
• Common (Other): Gingival hyperplasia, coarsening of facial features, hirsutism.
• Gastrointestinal: Nausea, vomiting, constipation.
• Dermatological: Skin rashes ranging from maculopapular to morbiliform. Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), can occur and require immediate drug discontinuation.
• Hematologic: Thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia.
• Hepatic: Hepatitis, liver damage, elevated liver enzymes.
• Other: Lymphadenopathy, osteomalacia (due to altered vitamin D metabolism), systemic lupus erythematosus (SLE).

Drug interaction

Phenytoin is a potent inducer of hepatic cytochrome P450 enzymes (e.g., CYP2C9, CYP2C19, CYP3A4) and is also a substrate for these enzymes, leading to a vast array of complex interactions.

• Drugs that may INCREASE phenytoin levels: Amiodarone, chloramphenicol, chlordiazepoxide, cimetidine, diazepam, disulfiram, estrogens, fluconazole, isoniazid, methylphenidate, omeprazole, phenothiazines, salicylates, sertraline, sulfonamides, ticlopidine, tolbutamide, warfarin.
• Drugs that may DECREASE phenytoin levels: Carbamazepine, chronic alcohol abuse, reserpine, rifampin, sucralfate, theophylline.
• Drugs whose levels are DECREASED by phenytoin: Antifungals (e.g., itraconazole, ketoconazole), oral contraceptives, corticosteroids, cyclosporine, digoxin, disopyramide, doxycycline, furosemide, lamotrigine, levothyroxine, methadone, mexiletine, quinidine, rifampin, theophylline, vitamin D, warfarin.
• Serum Folate: Phenytoin can cause folate deficiency.

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should never take a double dose to make up for a missed one.
• Maintaining a consistent dosing schedule is critical to stabilizing serum drug concentrations.

Overdose

Phenytoin overdose is a medical emergency, primarily manifesting as central nervous system toxicity.

• Symptoms: Nystagmus, ataxia, dysarthria, blurred vision, nausea, slurred speech, lethargy. At progressively higher levels (>30 mcg/mL), patients may experience hallucinations, hyperglycemia, metabolic acidosis, and eventually coma and fatal cardiorespiratory arrest.
• Treatment: There is no specific antidote. Management is supportive and includes securing the airway, ensuring adequate ventilation, and maintaining hemodynamic stability. 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.

Storage

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep the oral suspension in its original container. Do not freeze.
• Keep all medications out of the reach of children and pets.

Disclaimer

This information is intended for educational and informational purposes for healthcare professionals only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified physician or other authorized health provider with any questions you may have regarding a medical condition or therapeutic regimen. Never disregard professional medical advice or delay in seeking it because of something you have read here. The prescribing physician remains the ultimate authority regarding a patient’s treatment plan.

Reviews

• “As a neurologist with over 20 years of practice, Dilantin remains a fundamental tool in my armamentarium for managing focal and tonic-clonic seizures. Its predictable pharmacokinetics, when monitored correctly, allow for fine-tuned control. The main challenge is navigating its non-linear metabolism and numerous drug interactions, which requires vigilance.” – Dr. A. Reynolds, MD, Neurology
• “The efficacy of IV phenytoin for terminating active seizure clusters in the emergency department is well-established. While we now have newer agents, its rapid onset of action and familiarity make it a go-to choice, provided it is infused with cardiac monitoring due to the risk of hypotension and arrhythmia.” – J. Miller, PharmD, BCPS
• “Managing my son’s epilepsy with Dilantin has provided stability for years after other medications failed. The requirement for regular blood tests is a small price to pay for the seizure freedom he now experiences. We are diligent about his oral hygiene to manage the gum overgrowth side effect.” – Parent of a patient