Cardiovascular safely of fexofenadine HCl

被引:61
作者
Pratt, CM
Mason, J
Russell, T
Reynolds, R
Ahlbrandt, R
机构
[1] Baylor Coll Med, Dept Internal Med, Cardiol Sect, Houston, TX 77030 USA
[2] Hoechst Marion Roussel, Dept Clin Res, Kansas City, MO USA
关键词
D O I
10.1016/S0002-9149(99)00124-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fexofenadine Hd 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), res In Twelve-lead electrocardiographic delta were collected once before and after dosing or serially throughout these studies. Outliers were defined as QT(c) >440 ms with a greater than or equal to 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 torsades de pointes wets 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. (C) 1999 by Excerpta Medico, Inc.
引用
收藏
页码:1451 / 1454
页数:4
相关论文
共 23 条
[1]  
BASTECKY J, 1990, INTERNAL MED, V3, P266
[2]  
Bazett HC, 1920, HEART-J STUD CIRC, V7, P353
[3]   Efficacy and safety of fexofenadine hydrochloride for treatment of seasonal allergic rhinitis [J].
Bernstein, DI ;
Schoenwetter, WF ;
Nathan, RA ;
Storms, W ;
Ahlbrandt, R ;
Mason, J .
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 1997, 79 (05) :443-448
[4]   Effectiveness and safety of fexofenadine, a new nonsedating H1-receptor antagonist, in the treatment of fall allergies [J].
Bronsky, EA ;
Falliers, CJ ;
Kaiser, HB ;
Ahlbrandt, R ;
Mason, JM .
ALLERGY AND ASTHMA PROCEEDINGS, 1998, 19 (03) :135-141
[5]   ALLERGIC RHINITIS [J].
DRUCE, HM ;
KALINER, MA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1988, 259 (02) :260-263
[6]  
*HOECHST MAR ROUSS, 1997, PHYS DESK REF, P1284
[7]  
*HOECHST MAR ROUSS, FEX HCI INT SUMM SAF
[8]   CHANGES IN THE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PHARMACODYNAMICS OF TERFENADINE WITH CONCOMITANT ADMINISTRATION OF ERYTHROMYCIN [J].
HONIG, PK ;
WOOSLEY, RL ;
ZAMANI, K ;
CONNER, DP ;
CANTILENA, LR .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 52 (03) :231-238
[9]   TERFENADINE-KETOCONAZOLE INTERACTION - PHARMACOKINETIC AND ELECTROCARDIOGRAPHIC CONSEQUENCES [J].
HONIG, PK ;
WORTHAM, DC ;
ZAMANI, K ;
CONNER, DP ;
MULLIN, JC ;
CANTILENA, LR .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1993, 269 (12) :1513-1518
[10]  
*JANSS PHARM INC, 1997, PHYS DESK REF, P1341