Frequency of high-risk use of QT-prolonging medications.
OBJECTIVE
Prolongation of the QT interval has been associated with increased risk of torsades de pointes and death. Concurrent use of more than one QT-prolonging drug or a QT-prolonging drug with a drug that alters its pharmacokinetic profile is an important risk factor for adverse outcomes.


METHODS
Using a representative sample of 2 million health plan members from 10 health maintenance organizations with pharmacy benefits between January 1999 and July 2001, we identified potential drug interactions involving QT-prolonging medications. Prescription claims overlapping by at least 7 days for either 2 or more QT-prolonging drugs or a QT-prolonging drug with a drug that alters its clearance were considered potential drug interactions. We determined the number of drug interactions overall and the number of these interactions involving patients with other risk factors for torsades de pointes.


RESULTS
A total of 48 465 potential drug interactions were identified in 10 415 (4.6%) of the 228 550 patients with at least one prescription for a QT-prolonging drug. Amitriptyline was involved in 37 859 (78.1%) of the drug interactions. Of all potential drug interactions, 43 689 (90.1%) occurred in patients with at least one other risk factor for torsades de pointes, and 1053 (2.2%) were listed as a contraindicated combination in product labeling.


CONCLUSIONS
Potential drug interactions involving currently marketed QT-prolonging drugs occurred in 4.6% of patients who had a prescription for a QT-prolonging medication. The findings suggest several areas for targeted interventions to decrease the potential risk from QT-prolonging medications.
Allen LaPointe
Nancy M
NM
Duke Center for Education and Research on Therapeutics, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. allen003@mc.duke.edu
Curtis
Lesley H
LH
Chan
K Arnold
KA
Kramer
Judith M
JM
Lafata
Jennifer Elston
JE
Gurwitz
Jerry H
JH
Raebel
Marsha A
MA
Platt
Richard
R
D000367:Age Factors; D000368:Aged; D000639:Amitriptyline / Q000009:adverse effects; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000928:Antidepressive Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006279:Health Maintenance Organizations; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D010045:Outpatients; D012307:Risk Factors; D012737:Sex Factors; D016171:Torsades de Pointes / Q000139:chemically induced
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000639:Amitriptyline