How to manage seizures with phenytoin?

From the Guidelines

Phenytoin should be used with caution and as part of a comprehensive treatment plan for managing seizures, considering its potential side effects and interactions, and prioritizing the use of valproate or levetiracetam in cases of benzodiazepine-resistant status epilepticus, as suggested by the most recent evidence 1.

Key Considerations for Phenytoin Use

• The typical adult maintenance dose is 300-400 mg daily (4-6 mg/kg/day), usually divided into once or twice daily dosing.
• Treatment begins with a loading dose of 15-20 mg/kg given intravenously at a maximum rate of 50 mg/minute in emergency situations to rapidly achieve therapeutic levels.
• For oral maintenance therapy, start with 300 mg daily and adjust based on clinical response and serum levels, aiming for a therapeutic range of 10-20 mcg/mL.
• Phenytoin works by blocking voltage-dependent sodium channels in neurons, which stabilizes the neuronal membrane and prevents the spread of seizure activity.

Potential Side Effects and Interactions

• Common side effects include gingival hyperplasia, hirsutism, rash, ataxia, and nystagmus.
• Long-term use may cause vitamin D deficiency, osteoporosis, and peripheral neuropathy.
• Regular monitoring of drug levels is essential due to phenytoin's non-linear pharmacokinetics and narrow therapeutic index.
• Phenytoin interacts with many medications through hepatic enzyme induction, so a thorough medication review is necessary when starting treatment.

Alternative Treatment Options

• Valproate may be considered for refractory convulsive status epilepticus if benzodiazepines fail, as it can be given more quickly with fewer adverse effects compared to phenytoin or fosphenytoin 1.
• Levetiracetam is also a viable option for managing seizures, particularly in cases of benzodiazepine-resistant status epilepticus, as it has been shown to be effective in achieving seizure cessation in approximately half of all patients 1.

From the FDA Drug Label

In adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg per minute The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6 to 8 hours Therapeutic effect without clinical signs of toxicity occurs more often with serum total concentrations between 10 and 20 mcg/mL Determination of phenytoin serum levels is advised when using phenytoin in the management of status epilepticus and in the subsequent establishment of maintenance dosage

To manage seizures with phenytoin, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, followed by maintenance doses of 100 mg every 6 to 8 hours.

• The rate of administration should not exceed 50 mg per minute in adults.
• Serum phenytoin concentrations should be monitored to establish the optimal maintenance dosage and to minimize the risk of toxicity.
• The goal is to achieve serum total concentrations between 10 and 20 mcg/mL for optimal therapeutic effect without clinical signs of toxicity 2.

From the Research

Managing Seizures with Phenytoin

To manage seizures with phenytoin, several factors must be considered, including the dosage, administration method, and potential side effects.

• Dosage and Administration: Phenytoin can be administered intravenously to achieve rapid therapeutic concentrations 3, 4. The typical loading dose is 15-20 mg/kg, which can be infused at a rate of 30-50 mg/min 3.
• Efficacy: Phenytoin has been shown to be effective in managing status epilepticus, with success rates comparable to those of levetiracetam and valproate 5, 6.
• Side Effects: Phenytoin can cause hypotension, particularly in older patients, but is generally considered safe when administered properly 3, 4.
• Comparison to Other Treatments: Studies have compared phenytoin to other treatments, such as levetiracetam and valproate, with varying results 5, 6, 7.
• Pediatric Use: Phenytoin is also used in children, although there is a lack of evidence for its use in this population, and it is associated with significant side effects 7.

Key Considerations

When managing seizures with phenytoin, it is essential to monitor serum concentrations to ensure therapeutic levels are maintained 3, 4. Additionally, patients should be closely monitored for potential side effects, such as hypotension.

• Monitoring: Regular monitoring of serum phenytoin concentrations and patient vital signs is crucial to ensure safe and effective treatment 3, 4.
• Dose Adjustment: Dose adjustments may be necessary to maintain therapeutic serum concentrations and minimize side effects 3, 4.
• Alternative Treatments: In some cases, alternative treatments, such as levetiracetam or valproate, may be considered, particularly if phenytoin is not effective or is associated with significant side effects 5, 6, 7.