Drug Interaction Report

MONITOR: There is clinical evidence that eslicarbazepine acetate can prolong the PR interval of the electrocardiogram (ECG) in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta blockers, calcium channel blockers, atazanavir, lopinavir, digoxin, lacosamide, mefloquine) may result in additive effects and increased risk of conduction disturbances and atrioventricular (AV) block. In phase III adult adjunctive epilepsy studies in patients who received eslicarbazepine acetate 400 mg, 800 mg, or 1200 mg per day, mean increases in the PR interval at the end of 12 weeks of maintenance treatment were 2.4 msec, 1.3 msec, and 2.6 msec, respectively, compared to 0.6 msec in the placebo group. PR interval values greater than 200 msec at study end that were not present at baseline were observed in 0.8% and 0.2% of patients treated with eslicarbazepine acetate and placebo, respectively. In a clinical pharmacology ECG trial of healthy subjects who received either the maximum recommended daily dose of eslicarbazepine acetate (1200 mg), two times the maximum recommended daily dose of eslicarbazepine acetate (2400 mg) or placebo for five days, the maximum mean placebo-adjusted increase in the PR interval on day 5 was 4.4 msec at 5 hours post-dose for the 1200 mg group, and 8.2 msec at 3 hours post-dose for the 2400 mg group. Excessive PR interval prolongation can result in AV block. Cases of AV block have been reported in post-marketing experience.

MANAGEMENT: Caution is advised if eslicarbazepine is used concomitantly with other agents that prolong the PR interval, especially in the elderly and patients with known conduction problems (e.g., marked first-degree AV block; second-degree or higher AV block; sick sinus syndrome without pacemaker), or a history of syncope, arrhythmia or severe cardiac disease such as myocardial ischemia or heart failure. Patients should be advised to notify their doctor if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.