Drug Interactions between lamotrigine and propafenone

MONITOR: In vitro studies have shown that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations. Lamotrigine has shown in vitro effects on the human cardiac sodium channels similar to that of other Class 1B antiarrhythmic drugs. In healthy individuals, a thorough QT study did not show slowed ventricular conduction (widen QRS) with lamotrigine; however, the risk of slow ventricular conduction and proarrhythmias, including sudden death may be increased in patients with structural heart disease or myocardial ischemia. Based on this data, there is a concern that concomitant use of other sodium channel blockers may increase the risk of proarrhythmias.

MANAGEMENT: Caution and clinical monitoring are recommended if concomitant use of other sodium channel blockers is needed. Due to the potential for increased risk of proarrhythmias, the manufacturer recommends lamotrigine be avoided in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome or other sodium channelopathies). A joint task force of the International League Against Epilepsy and the American Epilepsy Society issued an advisory on Feb 25, 2021, for healthcare professionals in response to the FDA safety warning on the cardiac effects of lamotrigine. For patients under 60 years with no cardiac risk factors, they advise that clinicians should prescribe lamotrigine as usual. For patients with cardiac risk (over 60 years and under 60 years with known cardiac disease or significant risk factors), they advise clinicians to consider obtaining an ECG prior to initiating lamotrigine and repeating ECG as the serum lamotrigine level approaches the upper limit of the therapeutic range and/or with concomitant use of other sodium channel blockers or substances known to impair atrioventricular and/or intra-ventricular cardiac conduction. They also advise clinicians to consider obtaining an ECG and/or cardiology consult in patients with sudden onset syncope or pre-syncope with loss of muscular tone without a clear vasovagal or orthostatic cause. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate an irregular heart rhythm such as dizziness, lightheadedness, fainting, palpitation, shortness of breath, or syncope.