Drug Interaction Report

MONITOR CLOSELY: Dolasetron has been shown to cause dose-dependent prolongation of the PR and QRS intervals. There have been reports of second- and third-degree atrioventricular block, cardiac arrest, and serious ventricular arrhythmias including fatalities in both adult and pediatric patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta blockers; calcium channel blockers; some protease inhibitors such as atazanavir, lopinavir and saquinavir; digitalis; lacosamide; mefloquine; moricizine) or QRS interval (e.g., flecainide; moricizine; quinidine) may result in additive effects and increased risk of bradycardia and heart block. Other risk factors include underlying structural heart disease, preexisting conduction abnormalities, advanced age, sick sinus syndrome, atrial fibrillation with slow ventricular response, and myocardial ischemia. In a study of 80 healthy adult subjects, maximum mean difference in PR interval from placebo after baseline-correction was 9.8 ms and 33.1 ms for the 100 mg and supratherapeutic 300 mg dose of dolasetron, respectively. The maximum mean difference in QRS interval from placebo after baseline-correction was 3.5 ms for the 100 mg dose and 13 ms for the supratherapeutic 300 mg dose of dolasetron. Over 25% of the subjects treated with the 300 mg dose had an absolute PR over 200 ms and absolute QRS over 110 ms after treatment. A change from baseline of 25% or greater was noted in several of these subjects.

MANAGEMENT: Caution is advised if dolasetron is used concomitantly with other agents that prolong the PR or QRS interval, especially in the elderly and patients with known risk factors. An ECG should be obtained in these patients before initiating dolasetron and periodically during treatment. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. Dolasetron should be avoided in patients with complete heart block or at risk for complete heart block, unless they have an implanted pacemaker.