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Fexofenadine HCl is the acid metabolite of terfenadine (Seldane). The effect of this recently approved nonsedating antihistamine on the corrected QT interval (QTc) 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 QTc > 440 ms with a > or = 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 QTc. Longer term studies indicated no statistically significant QTc 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 QTc 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 QTc and no statistically significant increases in mean QTc compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc 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 QTc, even at doses > 10-fold higher than that is efficacious for SAR.

Fexofenadine HCl is a new, nonsedating H1-receptor antagonist approved for treatment of seasonal allergic rhinitis (SAR). In a double-blind, randomized, placebo-controlled, multicenter trial, 588 patients with fall SAR rated the severity of their symptoms using a scoring system at a screening visit and during a 3-day placebo lead-in period. Patients who did not respond to placebo and met symptom severity criteria were randomized to receive placebo or fexofenadine HCl at 40, 60, or 120 mg bid at 7:00 a.m. and 7:00 p.m. for 14 days. Patients continued to rate the severity of their symptoms immediately before receiving each dose (at trough). A total of 545 patients were included in an intent-to-treat analysis. The change from baseline in the primary efficacy variable (average daily 7:00 p.m. reflective symptom scores) was significantly greater in patients receiving all dosages of fexofenadine HCl than placebo (p < 0.01). All active dosages produced significant decreases (p < 0.05) in secondary end points: 7:00 a.m. reflective symptom scoring; 7:00 a.m. and 7:00 p.m. scoring 1-hour before dose; and bedtime scoring 1-3 hours after the 7:00 p.m. dose. All dosages of fexofenadine HCl were well tolerated, and no effect on QTc was observed. In conclusion, fexofenadine HCl is safe and effective in the treatment of fall SAR, with 60 mg bid being the optimal therapeutic dosage.

Background: H1-receptor antagonists are effective for the treatment of seasonal allergic rhinitis. In rare circumstances, some second-generation H1-receptor antagonists have been associated with prolongation of the corrected QT interval (QTc), thus increasing the risk of ventricular arrhythmias. Fexofendine HCl, the carboxylic acid metabolite of terfenadine, is a new second-generation antihistamine that is nonsedating and does not cause electrocardiographic effects., Objective: To investigate the clinical efficacy and safety of fexofenadine HCl in the treatment of ragweed seasonal allergic rhinitis and to characterize the dose-response relationship of fexofenadine HCl at dosages of 60, 120, and 240 mg bid., Methods: A multicenter, 14-day, placebo-controlled, double-blind trial was conducted with patients suffering from moderate to severe ragweed seasonal allergic rhinitis who met symptom severity criteria after a 3-day placebo baseline period. Patients with minimal or very severe symptoms during the baseline period were excluded. Patients were randomized to receive fexofenadine HCl (60, 120, or 240 mg bid) or placebo at 12-hour dosing intervals (7:00 AM and 7:00 PM). The primary efficacy measure was patient-assessed 12-hour reflective total symptom score before the evening dose (trough)., Results: Five hundred seventy patients completed the trial. Fexofenadine HCl at each dosage provided significant improvement in total symptom score (P < or = .003) and in all individual nasal symptoms compared with placebo. The frequency of adverse events was similar among fexofenadine HCl and placebo groups, with no dose-related trends. No sedative effects or electrocardiographic abnormalities, including prolongations in QTc were detected., Conclusions: Fexofenadine HCl is both effective and safe for the treatment of ragweed seasonal allergic rhinitis. Because there was no additional efficacy at higher dosages, 60 mg bid appears to be the optimal therapeutic dosage for these patients.