What is the next step in managing a patient with progressive seizures on Keppra (levetiracetam) 500 mg twice a day and dexamethasone 4 mg?

From the Guidelines

The next step in managing a patient with progressive seizures on Keppra (levetiracetam) 500 mg twice daily and dexamethasone 4 mg would be to increase the Keppra dosage to 1000 mg twice daily, as the current dose is at the lower end of the therapeutic range and the patient's seizures are not adequately controlled, as suggested by the most recent guidelines 1. This adjustment is necessary because levetiracetam has a wide therapeutic window, allowing for significant dose increases with minimal risk of toxicity. Some key points to consider in the management of this patient include:

• The choice of anticonvulsant agents has become wider with more drugs available over recent years, but there is a lack of robust, randomised, controlled evidence to support the choice of the optimal antiepileptic drug for the treatment of seizures in patients with brain tumours 1.
• Levetiracetam has become the drug of first choice at most neuro-oncology centres in recent years, although psychiatric side-effects in some patients remain a concern 1.
• Patients and caregivers should be instructed how to behave and whom to contact in case of recurrent seizures, and the patient should undergo urgent neuroimaging (MRI with contrast if possible) to evaluate for underlying structural causes of the seizures, particularly given the concurrent dexamethasone use which suggests possible intracranial pathology such as a tumor or inflammation.
• Blood levels of levetiracetam should be checked to ensure therapeutic concentrations, and if seizures continue despite dose optimization, adding a second antiepileptic drug such as lacosamide or valproate should be considered, as lacosamide may assume a larger role as an add-on treatment for patients whose seizure disorder is not controlled by monotherapy 1. Throughout this process, the patient requires close monitoring for breakthrough seizures, medication side effects, and potential drug interactions, and the dexamethasone should be continued at the current dose until the underlying etiology is better understood, as abrupt discontinuation could worsen cerebral edema if present.

From the FDA Drug Label

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID) Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg.

The patient is currently taking Keppra 500 mg twice a day, which is the initial recommended dose. To manage and prevent progressive seizures, the dose of Keppra can be increased by 1000 mg/day every 2 weeks to a maximum recommended daily dose of 3000 mg.

• The next step would be to increase the Keppra dose to 1000 mg twice a day (2000 mg/day) and monitor the patient's response.
• If seizures continue to progress, further dose increments can be made every 2 weeks, up to the maximum recommended daily dose of 3000 mg. 2

From the Research

Managing Progressive Seizures in a Patient with Brain Tumor

The patient is currently on Keppra (levetiracetam) 500 mg twice a day and dexamethasone 4 mg, but is experiencing more seizures. To manage and prevent seizures, consider the following options:

• Increase the dose of levetiracetam: According to the study 3, levetiracetam can be increased up to 5000 mg per day, and its pharmacokinetic characteristics make its clinical use simple and straightforward.
• Monitor liver function: Although levetiracetam is not primarily metabolized in the liver, severe liver injury can occur, as reported in the study 4. Monitoring of serum transaminase values may be helpful.
• Consider alternative antiepileptic drugs: The study 5 suggests that levetiracetam may not be effective in reducing seizure incidence in patients with traumatic brain injury, subarachnoid hemorrhage, or intracerebral hemorrhage. However, it may be preferred in patients with supratentorial neurosurgery.
• Oral loading of levetiracetam: The study 6 demonstrates that oral loading of levetiracetam is well-tolerated and can rapidly yield serum concentrations thought to decrease seizure frequency.

Considerations for Patients with Liver Disease

For patients with epilepsy and chronic liver disease, levetiracetam may be an attractive therapeutic option, as observed in the study 7. However, it is essential to monitor liver function and adjust the dose according to tolerability and therapeutic response.

Next Steps

Based on the available evidence, the next steps in managing the patient's seizures could include:

• Consulting with a neurologist to discuss alternative treatment options and adjust the current medication regimen as needed.
• Monitoring the patient's liver function and adjusting the dose of levetiracetam accordingly.
• Considering oral loading of levetiracetam to rapidly achieve therapeutic serum concentrations.
• Evaluating the patient's response to treatment and adjusting the plan as necessary to achieve optimal seizure control.