What is the proper work-up for a patient experiencing recurrent seizures while taking levetiracetam (Keppra)?

From the Guidelines

For a patient on levetiracetam who experiences another seizure, the proper workup should begin with an immediate assessment of their current condition and seizure details, prioritizing stabilization and ensuring the patient is safe, as supported by the most recent evidence from 2024 1. The initial steps should include checking vital signs and ensuring the patient is stable.

• Review medication adherence and check levetiracetam blood levels to ensure therapeutic dosing, as subtherapeutic levels may contribute to breakthrough seizures.
• Increase the dose if needed, typically by 500-1000 mg/day up to a maximum of 3000 mg/day, divided into two doses, based on the patient's response and tolerance.
• Investigate potential seizure triggers such as sleep deprivation, alcohol use, or illness, which can exacerbate seizure activity. Some key points to consider in the management of seizures in patients on levetiracetam include:
• Perform a comprehensive metabolic panel to rule out electrolyte imbalances or other metabolic causes that may be contributing to the seizures.
• Consider an EEG to evaluate for changes in seizure patterns and a brain MRI if not recently done to exclude new structural abnormalities, as these can impact treatment decisions.
• If seizures persist despite optimal levetiracetam levels, adding a second anti-epileptic drug such as valproic acid or lamotrigine, starting at a low dose and titrating up as tolerated, may be necessary, as supported by evidence from studies such as 1 and 1. The goal of this approach is to address both immediate management and long-term seizure control, targeting potential pharmacological and physiological factors contributing to breakthrough seizures, and ultimately reducing morbidity and mortality, as emphasized in the most recent clinical policy from 2024 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Proper Work-up for Recurrent Seizures while taking Levetiracetam

• The proper work-up for a patient experiencing recurrent seizures while taking levetiracetam (Keppra) involves a thorough evaluation to identify the underlying cause of the seizures 2.
• This includes gathering information about the patient's medical history, seizure history, and current medication regimen, as well as performing laboratory and imaging studies as needed 3.
• Electroencephalography (EEG) is recommended for patients presenting with recurrent seizures, and neuroimaging may also be necessary to rule out underlying structural brain disease 3.
• The patient's antiepileptic drug (AED) regimen, including the dosage of levetiracetam, should be evaluated and adjusted as needed in consultation with a neurologist 2, 4.
• It is also important to consider potential side effects of levetiracetam, such as eosinophilia and fever, which may require discontinuation of the medication 5.

Considerations for Levetiracetam Dosage

• The dosage of levetiracetam may need to be adjusted in patients experiencing recurrent seizures, but the optimal loading dose is not well established 4.
• A study evaluating the safety and efficacy of different loading doses of levetiracetam in patients with benzodiazepine-refractory status epilepticus found no significant difference in seizure termination rates or recurrent seizure activity between different dosage groups 4.
• However, higher loading doses of levetiracetam (>40 mg/kg) were associated with a higher rate of intubation, suggesting that caution is needed when using high doses of this medication 4.

Importance of Communication and Follow-up

• Communication between emergency physicians, neurologists, and primary care physicians is critical for the continuity of care for patients with recurrent seizures 2.
• Patients should be followed up with after an emergency department visit to evaluate the effectiveness of their treatment plan and make any necessary adjustments 2.
• A thorough work-up and follow-up care can help to identify the underlying cause of recurrent seizures and optimize treatment with levetiracetam or other AEDs 2, 6.