 |
|
Drug-Induced Long QT Syndrome in Injection Drug Users Receiving Methadone
High Frequency in Hospitalized Patients and Risk Factors
Georg B. Ehret, MD;
Cathy Voide, MD;
Marianne Gex-Fabry, PhD;
Jocelyne Chabert, PhD;
Dipen Shah, MD;
Barbara Broers, MD;
Valérie Piguet, MD;
Thierry Musset, RN;
Jean-Michel Gaspoz, MD;
Arnaud Perrier, MD;
Pierre Dayer, MD;
Jules A. Desmeules, MD
Arch Intern Med. 2006;166:1280-1287.
Background Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown.
Methods We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation.
Results Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function.
Conclusions QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.
Author Affiliations: Divisions of Clinical Pharmacology and Toxicology (Drs Ehret, Voide, Chabert, Piguet, Dayer, and Desmeules), General Internal Medicine (Drs Ehret, Gaspoz, and Perrier), and Cardiology (Dr Shah) and Departments of Psychiatry, Clinical Research Unit (Dr Gex-Fabry) and Community Health (Dr Broers and Mr Musset), Geneva University Hospital, Geneva, Switzerland. Dr Ehret is currently with the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.
RELATED LETTERS
Methadone-Induced Long QT Syndrome vs Methadone-Induced Torsades de Pointes
Dan Justo
Arch Intern Med. 2006;166(20):2288.
EXTRACT
| FULL TEXT
QTc Prolongation in Human Immunodeficiency Virus–Infected Persons
Nicola Petrosillo, Francesco Paolo Lisena, and Pierangelo Chinello
Arch Intern Med. 2006;166(20):2288-2289.
EXTRACT
| FULL TEXT
QTc Prolongation Among Hospitalized Patients Receiving Methadone
John Schmittner and Mori J. Krantz
Arch Intern Med. 2006;166(20):2289.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial
Wedam et al.
Arch Intern Med 2007;167:2469-2475.
ABSTRACT
| FULL TEXT
Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen
Fanoe et al.
Heart 2007;93:1051-1055.
ABSTRACT
| FULL TEXT
QTc Prolongation Among Hospitalized Patients Receiving Methadone.
Schmittner and Krantz
Arch Intern Med 2006;166:2289-2289.
FULL TEXT
Methadone-Induced Long QT Syndrome vs Methadone-Induced Torsades de Pointes.
Justo
Arch Intern Med 2006;166:2288-2288.
FULL TEXT
QTc Prolongation in Human Immunodeficiency Virus-Infected Persons.
Petrosillo et al.
Arch Intern Med 2006;166:2288-2289.
FULL TEXT
Methadone and Prolonged QT Syndrome
JWatch General 2006;2006:2-2.
FULL TEXT
|
