What are the indications for loading antiepileptic (anticonvulsant) medication in a patient with recurrent seizures?

From the Guidelines

Loading antiepileptic drugs is recommended in patients with recurrent seizures, with the choice of administration route (oral versus parenteral) at the discretion of the emergency physician, based on the most recent evidence from 2024 1. When considering loading antiepileptic drugs, several factors should be taken into account, including the type of seizure, the patient's medical history, and the potential side effects of the medication.

• The most commonly used loading antiepileptic drugs include levetiracetam, fosphenytoin, and valproate, which have similar efficacy in treating seizures refractory to benzodiazepines, as stated in the 2024 clinical policy 1.
• Levetiracetam can be loaded orally with a dose of 1,500 mg, or intravenously with a dose of up to 60 mg/kg, with no significant difference in seizure recurrence rate between the two routes, as shown in a study from 2014 1.
• Fosphenytoin can be loaded intravenously with a dose of 18 PE/kg at a maximum rate of 150 PE/min, with fewer adverse events compared to phenytoin, as reported in the same 2014 study 1.
• Valproate can be loaded intravenously with a dose of up to 30 mg/kg at a maximum rate of 10 mg/kg/min, with transient local irritation at the injection site as a potential side effect, also from the 2014 study 1. The decision to load antiepileptic drugs should be made on a case-by-case basis, taking into account the individual patient's needs and medical history, and the most recent evidence available, which prioritizes the use of levetiracetam, fosphenytoin, or valproate as second-line agents in the management of adult patients presenting to the emergency department with seizures, as recommended in the 2024 clinical policy 1.

From the FDA Drug Label

The loading dose should be followed by maintenance doses of either fosphenytoin sodium injection or phenytoin [see Dosage and Administration (2. 4)]. Adult and Pediatric Status Epilepticus Dosing: Table 1 Status Epilepticus Loading Dosages Population Dosage Infusion rate Adult 15 mg PE/kg to 20 mg PE/kg 100 mg PE/min to 150 mg PE/min, do not exceed a maximum rate of 150 mg PE/min Pediatric (Birth to less than 17 years of age) 15 mg PE/kg to 20 mg PE/kg 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower For Non-emergent Loading and Maintenance Dosing: Adult loading dose is 10 to 20 mg PE/kg given IV or IM; initial maintenance dose is 4 to 6 mg PE/kg/day in divided doses Pediatric loading dose is 10 to 15 mg PE/kg at a rate of 1 to 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower); initial maintenance dose is 2 to 4 mg PE/kg every 12 hours at a rate of 1 to 2 mg PE/kg/min (or 100 mg PE/min, whichever is slower)

The indications for loading antiepileptic in a patient with recurrent seizure are:

• Status Epilepticus:
  • Adults: 15 mg PE/kg to 20 mg PE/kg at a rate of 100 mg PE/min to 150 mg PE/min
  • Pediatrics: 15 mg PE/kg to 20 mg PE/kg at a rate of 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower
• Non-emergent Loading and Maintenance Dosing:
  • Adults: 10 mg PE/kg to 20 mg PE/kg given IV or IM
  • Pediatrics: 10 mg PE/kg to 15 mg PE/kg at a rate of 1 mg PE/kg/min to 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower 2 2

From the Research

Indications of Loading Antiepileptic in Patients with Recurrent Seizure

• The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients 3.
• Oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (MHD), in patients with epilepsy 3, 4.
• Approximately two-thirds of patients reached effective levels of MHD 2 hours after receiving the oral loading, and all patients reached effective levels 4 hours after oxcarbazepine administration 3.
• Most patients maintained therapeutic MHD levels for at least 16 hours, and almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 hours 3.
• The risk of recurrent seizures should guide the use of antiepileptic drugs, and key risk factors for recurrence in adults include two unprovoked seizures occurring more than 24 hours apart, epileptiform abnormalities on electroencephalography, abnormal brain imaging, nocturnal seizures, or an epileptic syndrome associated with seizures 5.
• In patients with seizures that are not controlled with antiepileptic drugs, alternative treatments include surgical resection of the seizure focus, ketogenic diets, vagus nerve stimulators, and implantable brain neurostimulators 5.
• Levetiracetam, fosphenytoin, and valproate are effective and safe options for the treatment of benzodiazepine-refractory convulsive status epilepticus, with similar incidences of adverse events 6, 7.
• The efficacy and safety of these drugs do not differ significantly by age group, and any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus 7.