Cardiovascular safety of fexofenadine HCl

Background Certain first- and second-generation H-1-receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia. Objective To assess the effect of fexofenadine HCl, a new non-sedating antihistamine, on QTc. Methods Dose-tolerance, safety, and drug-interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve-lead ECG data were collected pre- and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a greater than or equal to 10 msec increase from baseline. Results Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120-180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b.d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t.d.) or ketoconazole (400 mg q.d.) after dosing to steady-state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for weeks. there were no dose-related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. Conclusion Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.