Can a patient take divalproex (valproate) and levetiracetam (Keppra) simultaneously?

From the Guidelines

Yes, patients can take divalproex (valproate) and levetiracetam (Keppra) simultaneously, as this combination is commonly prescribed for epilepsy management. These medications work through different mechanisms - divalproex increases GABA levels and blocks sodium channels, while levetiracetam binds to synaptic vesicle protein SV2A to reduce neurotransmitter release. When used together, they can provide more comprehensive seizure control than either medication alone, especially for patients with difficult-to-control epilepsy.

Key Considerations

• The combination of divalproex and levetiracetam has been shown to be effective in managing seizures, with studies demonstrating similar efficacy to other antiepileptic medication combinations 1.
• Patients should be aware of potential side effects, including drowsiness, dizziness, and coordination problems, which may be more pronounced with combination therapy.
• Regular blood tests are necessary to monitor divalproex levels and liver function, as recommended by clinical guidelines 1.
• Dosing should always be individualized by a healthcare provider based on seizure type, frequency, patient weight, and other factors.
• Patients should never adjust or discontinue either medication without medical supervision, as this could trigger breakthrough seizures.

Mechanism of Action

• Divalproex increases GABA levels and blocks sodium channels, which helps to reduce neuronal excitability and prevent seizures.
• Levetiracetam binds to synaptic vesicle protein SV2A, reducing neurotransmitter release and decreasing the likelihood of seizure activity.

Clinical Evidence

• Studies have demonstrated the efficacy and safety of using divalproex and levetiracetam in combination for epilepsy management, with minimal adverse effects reported 1.
• Clinical guidelines recommend the use of valproate, levetiracetam, or phenobarbital for urgent control of seizures, in addition to phenytoin/fosphenytoin 1.

From the Research

Simultaneous Administration of Divalproex and Levetiracetam

• The simultaneous administration of divalproex (valproate) and levetiracetam (Keppra) is a topic of interest in the treatment of epilepsy.
• According to a study published in 2009 2, levetiracetam can be combined with other anticonvulsants, including valproate, to enhance their protective activity without exacerbating side effects or pharmacokinetic interactions.
• This combination may be beneficial for patients with drug-resistant epilepsy, as it provides additional therapeutic benefits due to the novel mechanism of action of levetiracetam.
• Another study published in 2018 3 suggests that levetiracetam can be administered intravenously as soon as possible in patients with benzodiazepine-resistant status epilepticus, and if ineffective, another antiepileptic drug such as valproate can be added.

Efficacy and Safety of Combination Therapy

• A double-blind randomized clinical trial published in 2022 4 compared the efficacy of levetiracetam, lamotrigine, and sodium valproate in patients with juvenile myoclonic epilepsy.
• The results showed that levetiracetam and sodium valproate have similar efficacy, while lamotrigine had a higher rate of failure in controlling seizures and myoclonic jerks.
• The study suggests that levetiracetam can be a good alternative to sodium valproate, especially in women of childbearing age.

Important Considerations

• When administering divalproex and levetiracetam simultaneously, it is essential to monitor the patient's valproic acid serum concentration to prevent recurring seizures, as interactions with other medications can affect valproic acid levels 5.
• The choice of divalproex formulation is also crucial, as extended-release divalproex can be administered once-daily, while enteric-coated, delayed-release divalproex requires multiple daily doses to maintain therapeutic levels 6.