Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients

• Published in: The American journal of medicine Vol. 114; no. 2; pp. 135 - 141
• Main Authors: Curtis, Lesley H, Østbye, Truls, Sendersky, Veronica, Hutchison, Steve, Allen LaPointe, Nancy M, Al-Khatib, Sana M, Usdin Yasuda, Sally, Dans, Peter E, Wright, Alan, Califf, Robert M, Woosley, Raymond L, Schulman, Kevin A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2003; Elsevier; Elsevier Sequoia S.A
• Subjects: Adult; Aged; Amitriptyline - adverse effects; Anti-Bacterial Agents - adverse effects; Anti-Infective Agents - adverse effects; Antidepressive Agents, Second-Generation - adverse effects; Antidepressive Agents, Tricyclic - adverse effects; Biological and medical sciences; Clarithromycin - adverse effects; Cohort Studies; Drug Prescriptions - statistics & numerical data; Drug Synergism; Drug toxicity and drugs side effects treatment; Erythromycin - adverse effects; Female; Fluoxetine - adverse effects; Heart Conduction System - drug effects; Humans; Male; Medical sciences; Middle Aged; Ofloxacin - adverse effects; Outpatients; Patients; Pharmacology. Drug treatments; Polypharmacy; Prescription drugs; Torsades de Pointes - chemically induced; Toxicity: cardiovascular system; United States; United States; Heart; Human; QT interval; Wave burst; Arrhythmia; Toxicity; Prolonged QT interval; Cardiovascular disease; Conduction disorder; Excitability disorder; Antibiotic; Heart block; Heart disease; Cohort study; Antidepressant agent; Antibacterial agent
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(02)01455-9

Many drugs prolong the QT interval and increase the risk of torsade de pointes. Concurrent use of two or more of these drugs can further increase the risk, but the prevalence of concurrent prescription of QT-prolonging drugs is not known. Using the administrative claims database of a national pharmaceutical benefit manager, we conducted a retrospective cohort study in 4,825,345 subjects aged 18 years or older. After identifying 50 drugs with QT-prolonging potential, and an additional 26 drugs that inhibit the metabolic clearance of QT-prolonging drugs, we measured the frequency of overlapping prescriptions for two or more of these drugs in the outpatient setting in 1999. Nearly 1.1 million subjects (22.8%) filled 4.4 million prescriptions for QT-prolonging drugs. Of these, 103,119 subjects (9.4%) filled overlapping prescriptions for two or more of the drugs or for a QT-prolonging drug and another drug that inhibits its clearance; 7249 subjects (0.7%) filled overlapping prescriptions for three or more of these drugs. Twenty-two percent of subjects who filled overlapping prescriptions were aged 65 or older; 74% were women. Antidepressants were involved in nearly 50% of the cases. Concurrent prescription of QT-prolonging drugs is common in the outpatient setting, and antidepressants are involved in half of these cases. Large pharmaceutical claims databases are useful for detecting potentially harmful prescribing behaviors, but better clinical evidence on medication safety is needed before such a system can be implemented fully.