Title: QT lengthening and arrhythmias associated with fexofenadine
Abstract: Additional data should be mentioned with regard to the case reported by Yigal Pinto and colleagues (March 20, p 980) of QT lengthening and life-threatening arrhythmias associated with use of fexofenadine.1Pinto YM Van Gelder IC Heeringa M Crijns HJGM QT lengthening and life-threatening arrhythmias associated with fexofenadine.Lancet. 1999; 353: 980Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar These data were provided to us by Pinto and colleagues during two site visits, the last one on March 17, 1999. The patient has several risk factors for ischaemic heart diease which is the most frequent cause of ventricular arrhythmia (age >65 years, familial history of ischaemic heart disease, current smoking, and hypertension with left-ventricular hypertrophy). In addition, a coronary angiography in 1997 showed no coronary artery stenosis and a myocardial scintingraphy in 1998 showed an interoposterior defect (judged as false positive). A coronary angiogram done after the arrhythmic episodes revealed a long stenosis of the circumflex artery (although it was deemed not significant 40%), and myocardial perfusion imaging by a single photon emission computed tomography showed a large defect from the apex to the basal wall. These elements indicate that this patient had progression of coronary artery disease with a possible inferior myocardial infarction. Carvedilol, known to protect the heart via its β-blocking properties, had been discontinued. The first recorded episode of ventricular tachycardia occurred during a fexofenadine-free interval, 4 days after withdrawal of fexofenadine (mean terminal elimination half-life 11–16 h). The patient was advised to receive an internal cardioverter defibrillator, usually indicated for treatment of recurrent ventricular tachycardia. He was ultimately treated with a β-blocker and an inhibitor of angiotensin-converting enzyme before discharge. The QTc time was increased at baseline, a condition known to predispose to serious ventricular arrhythmias at any time. Subsequent electrocardiograms showed that the QTc time remained abnormally long without fexofenadine. The QTc intervals were calculated with the Bazett formula. The use of more up-to-date methods of QT adjustment2Karjalainen J Viitasalo M Mänttäri M Manninen V Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values.J Am Coll Cardiol. 1994; 23: 1547-1553Summary Full Text PDF PubMed Scopus (235) Google Scholar, 3Sagie A Larson MG Goldberg RJ Bengston JR Levy D An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study).Am J Cardiol. 1992; 70: 797-801Summary Full Text PDF PubMed Scopus (595) Google Scholar might be more appropriate in this case. For example, the highest reported QTc value during fexofenadine treatment (532 ms, heart rate 95 beats per min), when recalculated with the two other methods2Karjalainen J Viitasalo M Mänttäri M Manninen V Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values.J Am Coll Cardiol. 1994; 23: 1547-1553Summary Full Text PDF PubMed Scopus (235) Google Scholar, 3Sagie A Larson MG Goldberg RJ Bengston JR Levy D An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study).Am J Cardiol. 1992; 70: 797-801Summary Full Text PDF PubMed Scopus (595) Google Scholar (477 and 475 ms, respectively), is similar to the intervals reported at baseline or after the events. This result indicates no positive dechallenge or positive rechallenge with regard to QTc intervals in this case. It is also noteworthy that fexofenadine has undergone rigorous preclinical and clinical testing for cardiac events and was shown to have no significant QT lengthening effect, even at doses much higher than those prescribed. Although a causal relation can be rarely entirely excluded in such cases, we believe the multiple confounding factors in this case offer alternative explanations of the observed events, independently of fexofenadine administration. QT lengthening and arrhythmias associated with fexofenadineAuthors' reply Full-Text PDF