Abstract Details

Cardiovascular diseases are comorbid in patients with narcolepsy. Cardiovascular adverse effects are of concern with narcolepsy medications because of this comorbidity and most patients require lifelong pharmacotherapy. Pitolisant, a selective histamine 3 (H₃)-receptor antagonist/inverse agonist, increases histamine transmission in the brain. In a QT study of healthy volunteers, pitolisant (35.6mg/day) led to a mean increase of 4.2msec in QTc interval. This analysis further characterized the cardiac safety of pitolisant (maximum dose, 35.6mg/day) in adults with narcolepsy.

Pooled analysis included 166 patients (pitolisant, n=85; placebo, n=81). Mean change in heart rate from baseline to end-of-treatment was -0.5 beats/min with pitolisant and -0.2 beats/min with placebo (LS mean difference, -0.4; P=0.744). Mean change was also similar for pitolisant versus placebo in systolic (LS mean difference, 0.0; P=0.983) and diastolic (LS mean difference, -0.6; P=0.552) blood pressure, as was mean change in QTc interval (LS mean difference, 0.4; P=0.911). Cardiac adverse events with pitolisant included heart rate increase (n=4), right bundle branch block (n=1), sinus tachycardia (n=1), and palpitations (n=1), and with placebo included blood pressure increase (n=1). In the long-term study, mean change from baseline in QTc interval was 3.1msec at Month 6 (n=70) and 6.1 msec at Month 12 (n=67); 3 patients had a postbaseline increase >60msec but none had QTc >500msec.