Cardiovascular safety of fexofenadine HCl

Fexofenadine HCl is the acid metabolite of terfenadine (Seldane). The effect of this recently approved nonsedating antihistamine on the corrected QT interval (QT(c)) was evaluated in dose-tolerance, safety, and drug- interaction studies with healthy volunteers, and in clinical studies in patients with seasonal allergic rhinitis (SAR). Twelve-lead electrocardiographic data were collected once before and after dosing or serially throughout these studies. Outliers were defined as QT(c) >440 ms with a ≥10 ms increase from baseline. The recommended fexofenadine HCl dose is 60 mg twice daily. Fexofenadine HCl doses up to 800 mg once daily or 690 mg twice daily for 28 days resulted in no dose-related increases in QT(c). Longer term studies indicated no statistically significant QT(c) increases compared with placebo in patients receiving fexofenadine HCl 80 mg twice daily for 3 months, 60 mg twice daily for 6 months, or 240 mg once daily for 12 months. Interaction studies showed no significant increases in QT(c) when fexofenadine HCl 120 mg twice daily was administered in combination with erythromycin (500 mg 3 times daily) or ketoconazole (400 mg once daily) after dosing to steady state (6.5 days). Clinical trials in patients with SAR (n = 1,160) treated with 40, 60, 120, or 240 mg twice-daily fexofenadine HCl or placebo indicated no dose-related increases: in QT(c) and no statistically significant increases in mean QT(c) compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated forsades de pointes was observed. The frequency and magnitude of QT(c) outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, we conclude that fexofenadine HCl has no significant effect on QT(c), even at doses > 10-fold higher than that is efficacious for SAR.