Terfenadine-associated ventricular arrhythmias and QTc interval prolongation. A retrospective cohort comparison with other antihistamines among members of a health maintenance organization.
This study compared the occurrence of syncope, ventricular arrhythmias, and corrected QT interval (QTc) prolongation over a 2 1/2-year period in persons prescribed terfenadine versus other prescription antihistamines among 265,000 members of the Harvard Community Health Plan (HCHP), the largest staff-model health maintenance organization in New England. HCHP maintains an automated medical record system with coded diagnoses for each ambulatory and hospital visit, and a similar automated pharmacy system with information for each member on all prescriptions filled at its pharmacies. Among 0.86 million exposure days of terfenadine and 1.04 million exposure days of other antihistamines, we found no excess risk of either clinical/arrhythmia events (odds ratio (OR), 0.86; 95% confidence interval (CI), 0.52 to 1.44) or QTc prolongation (OR, 1.00; 95% CI, 0.64 to 1.57) during courses of terfenadine versus those of other antihistamines. Joint courses of antihistamines and oral erythromycin were associated with an increased risk of QTc prolongation (OR, 2.33; 95% CI, 1.31 to 4.15), and there was a trend for this to be observed more frequently with terfenadine (OR, 2.37; 95% CI, 0.73 to 7.51; P = 0.14).
Hanrahan
J P
JP
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Choo
P W
PW
Carlson
W
W
Greineder
D
D
Faich
G A
GA
Platt
R
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D001900:Boston / Q000453:epidemiology; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D004917:Erythromycin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006279:Health Maintenance Organizations; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013575:Syncope / Q000139:chemically induced / Q000453:epidemiology; D016593:Terfenadine / Q000009:adverse effects*; D016896:Treatment Outcome; D018754:Ventricular Dysfunction / Q000139:chemically induced* / Q000453:epidemiology
D006634:Histamine H1 Antagonists; D004917:Erythromycin; D016593:Terfenadine