Maria G. Tanzi, PharmD
The potential cardiac effects of lamotrigine were added to its label late last year, and in March 2021, FDA released a drug safety communication highlighting the increased risk of arrhythmias in patients with heart disease who use lamotrigine. Data from in vitro testing showed that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations. In people with structural heart disease or myocardial ischemia, the medication could slow ventricular conduction and increase the risk of arrythmia, the agency warned.
“It was a bit confusing that this new warning seemed to be based entirely on in vitro data, and not any new clinical signal,” said Barry Gidal, PharmD, FAES, professor of pharmacy at the University of Wisconsin in Madison in a Neurology Today article. “Fairly quickly, it became obvious that there was a growing level of concern generated by this in the epilepsy community. Several epilepsy specialists said they were getting questions from patients who were concerned and were looking for guidance.”
FDA safety communication
FDA requested the in vitro data after receiving reports of abnormal electrocardiographs, cardiac arrest, loss of consciousness, and other adverse events with use of the drug. The drug safety communication recommends that clinicians evaluate whether the potential benefits of lamotrigine outweigh the potential risks for arrythmias in each patient, especially those with underlying cardiac issues. It also advises patients not to stop taking the medication without first discussing the risk with their prescriber, and to seek medical help if they experience symptoms such as an abnormal heart rate, shortness of breath, dizziness, or fainting.
FDA is also evaluating whether other sodium channel blockers, such as carbamazepine, phenytoin, and topiramate, have similar effects on the heart and is requiring safety studies for those medications. In the interim, other sodium channel blockers should not be considered safer alternatives to lamotrigine without additional information on the safety of these agents, the agency said.
ILAE and AES offer clinicians some guidance
In response to the label update, the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) formed an advisory task force to evaluate the cardiac effects of lamotrigine and to advise health care professionals on how to minimize the cardiac safety risks associated with use of the drug.
In its advisory, the task force noted that although in vitro data indicate lamotrigine has Class 1B antiarrhythmic sodium channel blocking properties, no change has been observed in ventricular conduction (i.e., QRS conduction) or in QT (i.e., it does not prolong repolarization) in healthy individuals or in those with epilepsy without heart disease. On this basis, the task force determined that “there is not an apparent arrhythmia risk of lamotrigine therapy in healthy people without heart disease.”
The advisory also offers guidance on electrocardiogram (ECG) monitoring with lamotrigine use. The risk of undiagnosed asymptomatic cardiac disease in patients under age 60 is minimal in the absence of major cardiovascular risk factors, the task force stated, and for those over 60, an ECG may be considered before initiating lamotrigine. An ECG should also be considered for those under 60 with known cardiac disease or significant risk factors.
Nonspecific ECG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning and should not preclude patients from being prescribed lamotrigine, the task force wrote.
For patients with ECG findings that pose the greatest risks (e.g., second and third-degree heart block, left or right bundle branch block), the task force recommends a thorough cardiological investigation to determine if lamotrigine can be administered safely.
The advisory also comments on when to obtain an initial ECG and repeat ECGs.
Takeaways
Clinicians should be aware of the new safety warning for lamotrigine and carefully evaluate the benefits and risks of this treatment for their patients.
Since the current data for lamotrigine are limited (i.e., in vitro), additional safety information on use of lamotrigine in those with underlying cardiac conditions is needed, along with data for the other sodium channel blockers.