Case Series of Cardiac Complications During Fingolimod First Dose Observation Period

Background: Fingolimod is the first oral agent approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Fingolimod acts as a sphingosine-1-phosphate (S1P) receptor antagonist.   S1P receptors are found on T and B cells, in heart, in the lungs and on the eye.   The effects on the cardiovascular system have been well documented to be mostly bradycardia.  In both phase III studies of fingolimod, a decrease in heart rate was noted after the first dose and peaked at 4 to 5 hours after administration.   Because of these risks, the FDA has recommended that all patients receive monitoring during the 6 hours following the first dose administration.

Objectives: To describe our experience with continuous electrocardiographic monitoring of patients with RRMS starting on fingolimod. 

Methods: Since changes to the FDA recommendations for first dose observation, a total of 25 patients with RRMS at our center began treatment with fingolimod. After the first dose, all patients were observed for 6 hours with continuous electrocardiographic telemetry, vital signs were checked every hour, and 12 lead ECG performed before and after the 6-hour period.  A retrospective chart review revealed two patients with arrhythmias during this period, presented here.

Results: Two out of 25 patients developed arrhythmia that led to discontinuation of fingolimod. The first patient developed second degree atrio-ventricular block at 5 1/2 hours and the second patient had a sinus arrest with ventricular escape rhythm for 45 seconds. Both patients had no prior cardiac disease and were not taking other medications that may cause arrhythmia or bradycardia. These arrhythmias may have not been detected without continuous electrocardiographic telemetry.

Conclusions: We suggest considering continuous on-line electrocardiographic telemetry as the standard method for monitoring for potential arrhythmias in patients starting on fingolimod.  We also suggest considering an increase of the observation period >6 hours for patients starting fingolimod.