Administration of intravenous immunoglobulin (IVIG) in vivo-down-regulatory effects on the IL-1 system

Background Certain first- and second-generation H1-receptor antagonists arc 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 HCI, 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 >10 msec increase from baseline. Resldts Fexofenadine HC1 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 QTe increases in patients receiving fexofenadine HCI 80 mg b.d. for 3 months, 60 mg b.d. for 6 months, or 240 mg q.d. tor 12 months. No statistically significant increases in QTc were detected when fexofenadine HCI 120mg 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 HCI for 2 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 HCI and placebo were similar in all studies. No case offexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. Conclusion Fexofenadine HCI has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCI has no significant effect on QTc, even at doses much higher than those used in clinical practice.