Can Levetiracetam (Keppra) be administered with Lamotrigine (Lamictal)?

From the Guidelines

Keppra can be given with Lamictal, as there is no significant interaction between the two medications that would prevent their concurrent use. These medications are commonly prescribed together for epilepsy and seizure disorders as they work through different mechanisms and can have complementary effects. Keppra works by binding to a synaptic vesicle protein, while Lamictal affects sodium channels and inhibits the release of excitatory neurotransmitters. When used together, they may provide better seizure control than either medication alone, especially for patients with difficult-to-control epilepsy 1. However, patients should be aware that combining these medications may increase the risk of side effects such as dizziness, drowsiness, and coordination problems. Some key points to consider when giving Keppra with Lamictal include:

• The loading dose and route of administration for Keppra is 1,500 mg oral load, or rapid IV loading safe and well tolerated in doses up to 60 mg/kg 1.
• For Lamictal, a single oral load of 6.5 mg/kg can be given if the patient has been on Lamictal for more than 6 months without a history of rash or intolerance, and only off Lamictal for less than 5 days 1.
• Patients should be monitored for adverse effects, such as fatigue, dizziness, and nausea, and the dosages of both medications should be adjusted as needed to minimize side effects.
• Regular follow-up appointments are necessary to monitor drug levels and adjust dosages as needed. It's essential for patients to take both medications exactly as prescribed and not to stop either medication suddenly, as this could trigger seizures. By carefully managing the use of Keppra and Lamictal together, healthcare providers can help patients achieve better seizure control and improve their quality of life.

From the FDA Drug Label

Potential drug interactions between levetiracetam and other AEDs (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam. Levetiracetam had no effect on plasma concentrations of carbamazepine, valproate, topiramate, or lamotrigine.

Keppra (levetiracetam) can be given with Lamictal (lamotrigine), as there is no significant pharmacokinetic interaction between the two drugs, according to the FDA drug label 2.

From the Research

Combination of Keppra and Lamictal

• The combination of levetiracetam (Keppra) and lamotrigine (Lamictal) has been studied in various research papers 3, 4, 5, 6, 7.
• A study published in 2012 compared the efficacy and tolerability of levetiracetam and lamotrigine as monotherapy in patients with newly diagnosed focal or generalized epilepsy, but did not specifically examine their combination 3.
• However, a 2018 study found that levetiracetam/lamotrigine duotherapy was one of the two regimens more likely to be associated with at least 6 months of seizure freedom in patients with focal epilepsy 4.
• Another study published in 2022 compared the efficacy of levetiracetam, lamotrigine, and sodium valproate in patients with juvenile myoclonic epilepsy, and found that levetiracetam and sodium valproate had similar efficacy, while lamotrigine had a higher rate of failure in controlling seizures and myoclonic jerks 5.
• A 2012 study examined the pharmacokinetic variability of four newer antiepileptic drugs, including lamotrigine and levetiracetam, and found that age and comedication were important contributors to pharmacokinetic variability 6.
• A 2010 study evaluated the efficacy, tolerability, and cognitive effects of levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease, and found that levetiracetam had a benign neuropsychological side effect profile and was associated with improved cognitive performance 7.

Key Findings

• Levetiracetam and lamotrigine can be used together as duotherapy in patients with focal epilepsy 4.
• The combination of levetiracetam and lamotrigine may be effective in controlling seizures, but its efficacy and tolerability need to be carefully evaluated in individual patients 4, 5.
• Age and comedication can affect the pharmacokinetics of levetiracetam and lamotrigine, and therapeutic drug monitoring may be necessary to optimize their use 6.
• Levetiracetam has a benign neuropsychological side effect profile and may be a good option for patients with Alzheimer's disease and epileptic seizures 7.