Sex differences in incidence rates and referral ratios for first attack angina pectoris.

Sir, Fexofenadine is the active metabolite of the non-sedating antihistamine, terfenadine. Accumulation of terfenadine can cause prolongation of the QT interval and significant cardiac arrhythmias.1 Fexofenadine is reported to have no potential for QT interval disturbance.2 Phase II and III clinical trials in over 6000 patients showed no mean increases in mean QTc or serious cardiac arrhythmias when comparing fexofenadine with placebo groups.3 There has been one case report of ventricular tachycardia causally associated with exposure to fexofenadine in a patient prone to a long QTc interval.4 A recent search of AdisBase and MEDLINE did not reveal any other case reports of ventricular tachycardia associated with exposure to fexofenadine.5 The Drug Safety Research Unit used the technique of Prescription Event Monitoring to study events in patients prescribed fexofenadine following its launch in England in March 1997.6 A total of 35 817 green forms were posted to 8057 GPs who had written prescriptions for fexofenadine between March and August 1997. In all, 18 238 were returned, giving a response rate of 50.9%. The final cohort totalled 16 638 patients. Less than 1% of patients discontinued the drug because of intolerance, and there were no specific reports of drug interactions involving fexofenadine. All cardiac events were examined in detail, and eight that resolved on stopping fexofenadine were possible sideeffects: palpitations (three), chest pain (three), arrhythmia (one), and chest tightness (one). There were no reports of ventricular tachycardia, prolonged QT interval, or serious cardiac events. Our study of patients taking fexofenadine in routine clinical practice failed to show any serious adverse cardiac events that could have been a result of drug exposure. The characteristics of our cohort (age, concomitant medication, and indication for use of fexofenadine) suggest that, for this drug, the clinical trial population and the community patients are comparable except for the delivery of care. Although the study was on a large cohort, the response rate was only 51%, and this could introduce an under-reporting bias. With a very rare event, a few cases could make a big difference to the generation of a safety signal. Our results, the results from clinical trials, and a single case report from a drug now in widespread use suggest that, even if serious cardiac arrhythmias are associated with exposure to fexofenadine, they are very rare. In the absence of dedicated case registries, the only practicable way to detect such very rare events is the spontaneous reporting made by vigilant practitioners.