QT interval monitoring during clinical studies with mizolastine, a new H1 antihistamine.

Background: Some H1 antihistamines are at risk for rare but severe dysrhythmias due to an effect on the ventricular repolarization.

Objective: To present an overview of the QT interval monitoring performed during the clinical development of mizolastine, a new selective second-generation H1 antihistamine.

Methods: The ECGs database analysis of clinical studies conducted in volunteers and patients is summarized and focused on the results of reported studies and studies specifically designed for the assessment of the effect of mizolastine on cardiac repolarization, through the QT interval measurements. Mizolastine was orally administered up to 75 mg single dose and 40 mg repeated dose in healthy volunteers (i.e. 7. 5 and 4 times the recommended dose, respectively) and at a dose of 10 or 15 mg in patients.

Results: In healthy volunteers, no increased incidence of QTc values >440 msec or DeltaQTc >/=40 msec were recorded compared to placebo. No dose-related increase in QTc interval was observed. The ECG parameters were not modified by the co-administration of mizolastine with digoxin, diltiazem and erythromycin, when compared to the effect of each co-administered drug alone. In patients, the mean QTc interval changes from baseline did not significantly differ from placebo. In comparative studies vs. loratadine a similar incidence of out of range values was observed with mizolastine and loratadine.

Conclusion: ECG monitoring of volunteers and patients included in clinical studies conducted with mizolastine showed no significant effect of mizolastine on cardiac repolarization.