Should a patient experiencing a breakthrough seizure be loaded with Keppra (levetiracetam)?

From the Guidelines

Loading a patient experiencing a breakthrough seizure with Keppra (levetiracetam) is often appropriate, with a recommended loading dose of 1,500 mg oral load or rapid IV loading safe and well tolerated in doses up to 60 mg/kg, as evidenced by studies such as 1. When considering the management of breakthrough seizures, it is crucial to prioritize the patient's morbidity, mortality, and quality of life. In this context, the use of Keppra (levetiracetam) as a loading dose has been studied, and the evidence suggests that it is a viable option.

• The typical loading dose is 1,500 mg oral load, and rapid IV loading is safe and well tolerated in doses up to 60 mg/kg, as shown in 1.
• Keppra is generally preferred for loading due to its broad spectrum of activity against various seizure types, minimal drug interactions, linear pharmacokinetics, and relatively favorable side effect profile, including fatigue, dizziness, and rarely pain at the infusion site, as noted in 1.
• It has a rapid onset of action and achieves therapeutic levels quickly, making it an attractive option for managing breakthrough seizures.
• For patients already on Keppra who experience breakthrough seizures, increasing their current dose may be necessary rather than administering a loading dose, and it is essential to assess for potential triggers of breakthrough seizures such as medication non-compliance, sleep deprivation, alcohol withdrawal, or metabolic disturbances.
• The choice of administration route, whether oral or intravenous, depends on the clinical scenario and 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, as discussed in 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Breakthrough Seizure Management

• The decision to load a patient with Keppra (levetiracetam) after a breakthrough seizure should be based on the patient's specific medical history and the severity of the seizure.
• Studies have shown that levetiracetam can be an effective and safe alternative to traditional antiepileptic drugs like phenytoin in the management of status epilepticus and acute repetitive seizures 2, 3, 4.

Efficacy of Levetiracetam

• A study published in 2015 found that levetiracetam and phenytoin were equally effective in terminating seizure activity within 30 minutes of infusion 2.
• Another study published in 2020 found that levetiracetam had a higher efficacy rate than phenytoin in children with convulsive status epilepticus (77.6% vs 57.7%) 3.
• A systematic review and meta-analysis published in 2021 found that levetiracetam was more effective than phenytoin in achieving clinical seizure cessation within 60 minutes (pooled RR 1.08,95% CI 1.02-1.14) 4.

Safety Profile of Levetiracetam

• Levetiracetam has been shown to have a safer profile than phenytoin, with fewer cardiovascular side effects and a lower incidence of serious adverse events 3, 4.
• A study published in 2011 found that levetiracetam failed to control status epilepticus more often than valproate, but this finding was not consistent across all studies 5.

Clinical Considerations

• The choice of antiepileptic drug should be individualized based on the patient's specific needs and medical history.
• Levetiracetam may be a suitable alternative to phenytoin in patients who experience breakthrough seizures, particularly in those with a history of status epilepticus or acute repetitive seizures 2, 3, 4.
• Further studies are needed to fully establish the efficacy and safety of levetiracetam in the management of breakthrough seizures 5, 6.