Dilantin

Dilantin (phenytoin) is a cornerstone anticonvulsant medication with a long-standing history in neurological therapeutics. As a hydantoin derivative, it is primarily indicated for the management and prevention of tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures. Its mechanism of action involves the stabilization of neuronal membranes and the reduction of the maximal activity of brain stem centers responsible for the tonic phase of grand mal seizures, primarily through use-dependent blockade of voltage-gated sodium channels. This product card provides a comprehensive, expert-level overview for healthcare professionals to ensure its safe and effective clinical application.

Features

• Active Pharmaceutical Ingredient: Phenytoin sodium.
• Available Formulations: Oral capsules (30 mg and 100 mg strengths, extended-release), chewable tablets (50 mg), and an injectable solution (50 mg/mL).
• Pharmacokinetics: Exhibits saturable (non-linear), capacity-limited metabolism, primarily via the cytochrome P450 enzyme system (CYP2C9 and CYP2C19).
• Bioavailability: The extended-release capsules are formulated for once-daily dosing in stabilized patients, with a bioavailability of ~90% compared to the prompt-release oral forms.
• Half-life: Varies significantly with dose and serum concentration (average 22 hours for levels <10 mcg/mL; can extend to 60+ hours at higher, saturating concentrations).
• Protein Binding: Highly protein-bound (approximately 90%), primarily to albumin.

Benefits

• Provides effective prophylaxis and treatment for generalized tonic-clonic and partial seizures, reducing seizure frequency and severity.
• Offers a well-established safety and efficacy profile backed by decades of clinical use and research.
• The extended-release formulation supports enhanced adherence through convenient once-daily dosing in maintenance therapy.
• Rapid achievement of therapeutic levels is possible with a loading dose protocol in acute settings.
• Can be used as a first-line agent or as an adjunctive therapy in managing complex epilepsy cases.

Common use

Dilantin is FDA-approved for the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures. It is not effective for absence (petit mal) seizures. Its use is also well-documented in the prevention and treatment of seizures occurring during or following neurosurgery, including procedures for head trauma. Off-label, it may be utilized in the management of certain cardiac arrhythmias (e.g., those associated with digitalis toxicity), though this application has been largely superseded by other antiarrhythmics, and for neuropathic pain conditions such as trigeminal neuralgia.

Dosage and direction

Dosing is highly individualized and must be titrated based on therapeutic response and serum phenytoin level monitoring due to its non-linear pharmacokinetics.

• Adults: For patients not previously treated, a common starting dose is 100 mg of the extended-release capsule three times daily. Adjust dosage at 7- to 10-day intervals. Many adults can be maintained on 300-400 mg daily. A single daily dose is possible once the patient is stabilized on a dosage regimen using the 300 mg extended-release capsule.
• Pediatrics: Initial dose is 5 mg/kg/day in two or three divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. Maintenance dosing is often 4-8 mg/kg/day.
• Loading Dose: For rapid achievement of therapeutic levels in a non-emergent setting, an oral loading dose of 1 gram (1000 mg) is divided into three doses (400 mg, 300 mg, 300 mg) administered at 2-hour intervals.
• Administration: Oral capsules should be swallowed whole and not crushed or chewed. It is recommended to administer with food to minimize gastric upset. Consistent administration relative to meals is advised.

Critical Note: Therapeutic drug monitoring is essential. The generally accepted therapeutic serum concentration range for seizure control is 10-20 mcg/mL. Unbound (free) phenytoin monitoring is recommended in patients with conditions altering protein binding (e.g., renal failure, hypoalbuminemia).

Precautions

• Abrupt Withdrawal: Abrupt discontinuation may precipitate status epilepticus. Withdraw gradually to avoid this risk.
• Hepatic Impairment: Use with extreme caution; phenytoin is extensively metabolized by the liver. Reduced metabolism can lead to toxicity.
• Renal Impairment: Uremia may decrease protein binding, increasing the fraction of free (active) drug. Dose adjustments may be necessary based on free phenytoin levels.
• Elderly Patients: Often have decreased albumin and may require lower dosages and monitoring of free phenytoin levels.
• Endocrine: May elevate blood glucose levels and can lead to the development of osteomalacia due to altered vitamin D metabolism with long-term use.
• Porphyria: Should be avoided as it may exacerbate acute attacks.
• Driving and Operating Machinery: Patients should be cautioned about the potential for dizziness, drowsiness, and ataxia, which could impair these abilities.

Contraindications

Dilantin is contraindicated in patients with:

• 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 correlated 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.
• Dermatological: Skin rash (maculopapular or morbiliform), which can rarely progress to severe reactions like Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Discontinue at first sign of rash.
• Hematological: Megaloblastic anemia, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.
• Hepatic: Hepatitis, liver damage, jaundice.
• Gastrointestinal: Nausea, vomiting, constipation.
• Other: Lymphadenopathy, systemic lupus erythematosus, polyarthropathy.

Drug interaction

Phenytoin is a major substrate and inducer of hepatic enzymes (CYP2C9, CYP2C19, CYP3A4, UGT), leading to numerous and clinically significant interactions.

• Drugs that INCREASE Phenytoin Levels: Amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogens, fluoxetine, isoniazid, omeprazole, phenothiazines, salicylates (at high doses), sertraline, sulfonamides, ticlopidine, tolbutamide, warfarin, acute alcohol intake.
• Drugs that DECREASE Phenytoin Levels: Carbamazepine, chronic alcohol abuse, reserpine, sucralfate, 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 (e.g., delavirdine, efavirenz, indinavir, lopinavir/ritonavir, nevirapine, ritonavir, saquinavir).
• Other Notable Interactions: Concomitant use with valproic acid increases the free fraction of phenytoin and can also decrease the total phenytoin level.

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 for stable serum concentrations.

Overdose

• Symptoms: Toxicity is primarily cerebellar and vestibular. Symptoms include nystagmus, ataxia, dysarthria, drowsiness, lethargy, nausea, and vomiting. In severe cases, hypotension, coma, and death can occur. Death is due to respiratory and circulatory depression.
• Management: There is no specific antidote. Treatment is supportive and includes securing the airway, ensuring adequate ventilation, and maintaining hemodynamic stability. Gastric lavage may be beneficial if performed soon after ingestion. Hemodialysis is not effective due to high protein binding. Serum level monitoring is crucial to guide management.

Storage

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep the medication in its original container, tightly closed.
• Keep out of reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain unless instructed to do so.

Disclaimer

This information is intended for educational purposes and as a summary for healthcare professionals. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The prescribing physician should be consulted for specific dosing, indications, and management.

Reviews

• “Dilantin remains a workhorse in our epilepsy clinic. Its efficacy for tonic-clonic seizures is undeniable, but the non-linear kinetics demand vigilance in monitoring. The extended-release formulation has significantly improved patient compliance in our long-term management cases.” – Neurologist, 15 years of experience.
• “While newer agents have emerged, Dilantin’s rapid action via loading dose is invaluable in acute inpatient settings for seizure prophylaxis post-neurosurgery. We rely heavily on free level monitoring in our ICU patients with hypoalbuminemia.” – Clinical Pharmacist, Neuro-ICU.
• “Managing the drug interactions is a constant challenge, particularly in patients on polypharmacy. However, for the right patient, it provides effective and affordable seizure control. Patient education on gingival hyperplasia and oral hygiene is a must.” – General Practitioner.
• “The side effect profile, particularly the potential for severe cutaneous reactions and long-term cosmetic effects, requires a thorough risk-benefit discussion with patients. It’s a powerful drug that commands respect.” – Epileptologist.