What is the recommended dosage and management of phenytoin for seizure treatment?

From the Guidelines

Phenytoin should be dosed at 20 mg/kg divided in maximum doses of 400 mg every 2 h orally, or 18 mg/kg IV at a maximum rate of 50 mg/min for acute seizure management, with careful monitoring of serum levels to achieve a target concentration of 10-20 mcg/mL 1. The management of phenytoin for seizure treatment requires careful consideration of the dosage and administration route.

• The oral loading dose is typically 20 mg/kg divided in maximum doses of 400 mg every 2 h, while the IV loading dose is 18 mg/kg at a maximum rate of 50 mg/min 1.
• The choice of administration route (oral versus parenteral) depends on the discretion of the emergency physician, as there is a lack of evidence to support one route over the other in terms of preventing early recurrent seizure 1.
• Maintenance dosing should be individualized based on therapeutic drug monitoring, with regular blood level monitoring essential to avoid adverse effects and ensure efficacy 1.
• Common adverse effects of phenytoin include gingival hyperplasia, hirsutism, rash, ataxia, and cognitive impairment, and long-term use may lead to osteoporosis, peripheral neuropathy, and cerebellar atrophy 1.
• Phenytoin interacts with many medications through hepatic enzyme induction, potentially decreasing the effectiveness of oral contraceptives, warfarin, and certain antibiotics, and dosage adjustments are necessary for patients with hepatic impairment, the elderly, and those with hypoalbuminemia 1.
• The most recent and highest quality study, published in 2014, provides the best evidence for the management of phenytoin in seizure treatment 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Serum concentrations should be monitored in changing from extended phenytoin sodium capsules, USP to prompt phenytoin sodium capsules, USP, and from the sodium salt to the free acid form. Adult Dosage: Divided daily dosage: Patients who have received no previous treatment may be started on one 100 mg extended phenytoin sodium capsule, USP three times daily and the dosage then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be one capsule three to four times a day An increase up to two capsules three times a day may be made, if necessary. Once-a-day dosage: In adults, if seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules, USP daily, once-a-day dosage with 300 mg of extended phenytoin sodium capsules, USP may be considered The clinically effective serum level is usually 10 to 20 mcg/mL. The recommended dosage and management of phenytoin for seizure treatment is to start with one 100 mg extended phenytoin sodium capsule, USP three times daily and adjust the dosage to suit individual requirements, with a satisfactory maintenance dosage of one capsule three to four times a day.

• Key considerations include:
  • Monitoring serum concentrations when changing dosage forms or brands
  • Adjusting dosage based on individual requirements and serum levels
  • Considering once-a-day dosage with 300 mg of extended phenytoin sodium capsules, USP for adults who require this amount of drug daily
  • Using caution when interpreting total phenytoin plasma concentrations in patients with renal or hepatic disease
  • Adjusting dosage in elderly patients and pediatric patients as necessary 2

From the Research

Phenytoin Dosage and Management

• The recommended dosage of phenytoin varies depending on the type of seizure and the individual patient's response to the medication 3.
• For generalized tonic-clonic seizures, the mean plasma concentration of phenytoin necessary for complete control is 14 micrograms/mL 3.
• For partial seizures, the mean plasma concentration of phenytoin necessary for complete control is 23 micrograms/mL 3.
• Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus 4.

Monitoring and Administration

• Plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks 4.
• The half-life of phenytoin is less than 20 hours in low doses, but is prolonged in high doses, newborn infants, and elderly people 4.
• Phenytoin is usually administered intravenously to maintain the anticonvulsive effect in generalized tonic-clonic status epilepticus 5.
• Monitoring serum drug concentrations may provide a useful guide to dosage adjustments, particularly in the case of phenytoin, which shows dose-dependent kinetics within the therapeutic dosage range 6.

Safety and Efficacy

• Phenytoin has potentially adverse effects, including phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome 4.
• The efficacy of plasma concentrations of phenytoin varies with the type of seizure 3.
• Phenytoin appears to have similar efficacy to carbamazepine and valproate in the treatment of tonic-clonic seizures, with complete control reported in 50% of patients 7.
• Acute and dose-related central nervous system side effects occurred with equal frequency with carbamazepine, phenytoin, and valproate treatment 7.