This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (105)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Aging/ Geriatrics  • Adverse Effects  • Alert me on articles by topic

David N. Juurlink, MD, FRCPC; Muhammad Mamdani, PharmD, MPH; Alexander Kopp; Andreas Laupacis, MD, MSc; Donald A. Redelmeier, MD, MSc

JAMA. 2003;289:1652-1658.

Context  Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.

Objective  To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.

Design  Three population-based, nested case-control studies.

Setting  Ontario, Canada, from January 1, 1994, to December 31, 2000.

Patients  All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).

Main Outcome Measure  Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.

Results  During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).

Conclusions  Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.

Author Affiliations: Sunnybrook and Women's College Health Sciences Centre; the Clinical Epidemiology and Healthcare Research Program, and Departments of Medicine (Drs Juurlink, Laupacis, and Redelmeier), and Pharmacy (Dr Mamdani), University of Toronto; and the Institute for Clinical Evaluative Sciences (Drs Juurlink, Mamdani, Laupacis, and Redelmeier, and Mr Kopp), Toronto, Ontario.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria
Gallagher and O'Mahony
Age Ageing 2008;0:afn197v1-afn197.
ABSTRACT | FULL TEXT  

Generalizability of the Results of Randomized Trials
Weiss et al.
Arch Intern Med 2008;168:133-135.
FULL TEXT  

Compliance with National Guidelines for the Management of Drug Drug Interactions in Dutch Community Pharmacies
Buurma et al.
The Annals of Pharmacotherapy 2007;41:2024-2031.
ABSTRACT | FULL TEXT  

Evaluation of an Electronic Critical Drug Interaction Program Coupled with Active Pharmacist Intervention
Humphries et al.
The Annals of Pharmacotherapy 2007;41:1979-1985.
ABSTRACT | FULL TEXT  

START (screening tool to alert doctors to the right treatment) an evidence-based screening tool to detect prescribing omissions in elderly patients
Barry et al.
Age Ageing 2007;36:632-638.
ABSTRACT | FULL TEXT  

Guided Care for Multimorbid Older Adults: Kathleen Walsh Piercy, PhD, Editor
Boyd et al.
Gerontologist 2007;47:697-704.
ABSTRACT | FULL TEXT  

Evaluation of Pharmacokinetic Interactions Between Vildagliptin and Digoxin in Healthy Volunteers
He et al.
J Clin Pharmacol 2007;47:998-1004.
ABSTRACT | FULL TEXT  

Laboratory Evaluation of Potassium and Creatinine Among Ambulatory Patients Prescribed Spironolactone: Are We Monitoring for Hyperkalemia?
Raebel et al.
The Annals of Pharmacotherapy 2007;41:193-200.
ABSTRACT | FULL TEXT  

Practitioners' Views on Computerized Drug-Drug Interaction Alerts in the VA System
Ko et al.
J. Am. Med. Inform. Assoc. 2007;14:56-64.
ABSTRACT | FULL TEXT  

An Interaction Between Aspirin and Valproate: The Relevance of Plasma Protein Displacement Drug-Drug Interactions
Sandson et al.
Am. J. Psychiatry 2006;163:1891-1896.
FULL TEXT  

Use and Perceived Benefits of Handheld Computer-based Clinical References
Rothschild et al.
J. Am. Med. Inform. Assoc. 2006;13:619-626.
ABSTRACT | FULL TEXT  

Are Broad-Spectrum Fluoroquinolones More Likely To Cause Clostridium difficile-Associated Disease?
Dhalla et al.
Antimicrob. Agents Chemother. 2006;50:3216-3219.
ABSTRACT | FULL TEXT  

The Risk of Suicide With Selective Serotonin Reuptake Inhibitors in the Elderly
Juurlink et al.
Am. J. Psychiatry 2006;163:813-821.
ABSTRACT | FULL TEXT  

Outpatient Gatifloxacin Therapy and Dysglycemia in Older Adults
Park-Wyllie et al.
NEJM 2006;354:1352-1361.
ABSTRACT | FULL TEXT  

Adherence to black box warnings for prescription medications in outpatients.
Lasser et al.
Arch Intern Med 2006;166:338-344.
ABSTRACT | FULL TEXT  

Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis
Choudhry et al.
BMJ 2006;332:141-145.
ABSTRACT | FULL TEXT  

The Complexity and Cost of Drug Regimens of Older Patients Hospitalized With Heart Failure in the United States, 1998-2001
Masoudi et al.
Arch Intern Med 2005;165:2069-2076.
ABSTRACT | FULL TEXT  

An Overview of Psychotropic Drug-Drug Interactions
Sandson et al.
Psychosomatics 2005;46:464-494.
ABSTRACT | FULL TEXT  

Assessment of potential drug-drug interactions with a prescription claims database
Malone et al.
Am J Health Syst Pharm 2005;62:1983-1991.
ABSTRACT | FULL TEXT  

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)
Developed in Collaboration With the American Colle et al.
J Am Coll Cardiol 2005;46:1116-1143.
FULL TEXT  

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society
Hunt et al.
Circulation 2005;112:1825-1852.
FULL TEXT  

Hyperkalemia: A Review
Evans and Greenberg
J Intensive Care Med 2005;20:272-290.
ABSTRACT  

Clinical Practice Guidelines and Quality of Care for Older Patients With Multiple Comorbid Diseases: Implications for Pay for Performance
Boyd et al.
JAMA 2005;294:716-724.
ABSTRACT | FULL TEXT  

Prognostic Implications of Warfarin Cessation After Major Trauma: A Population-Based Cohort Analysis
Hackam et al.
Circulation 2005;111:2250-2256.
ABSTRACT | FULL TEXT  

Risk of Upper Gastrointestinal Hemorrhage in Warfarin Users Treated With Nonselective NSAIDs or COX-2 Inhibitors
Battistella et al.
Arch Intern Med 2005;165:189-192.
ABSTRACT | FULL TEXT  

Economic Grand Rounds: Drug-Drug Interactions: The Silent Epidemic
Sandson
Psychiatr. Serv. 2005;56:22-24.
FULL TEXT  

Acute Colchicine Intoxication During Clarithromycin Administration
Rollot et al.
The Annals of Pharmacotherapy 2004;38:2074-2077.
ABSTRACT | FULL TEXT  

Rates of Hyperkalemia after Publication of the Randomized Aldactone Evaluation Study
Juurlink et al.
NEJM 2004;351:543-551.
ABSTRACT | FULL TEXT  

Managing Hyperkalemia Caused by Inhibitors of the Renin-Angiotensin-Aldosterone System
Palmer
NEJM 2004;351:585-592.
FULL TEXT  

Drug-Drug, Drug-Dietary Supplement, and Drug-Citrus Fruit and Other Food Interactions: What Have We Learned?
Huang and Lesko
J Clin Pharmacol 2004;44:559-569.
ABSTRACT | FULL TEXT  

Observational Studies of Treatment Effectiveness: Some Cautions
Laupacis and Mamdani
ANN INTERN MED 2004;140:923-924.
FULL TEXT  

Editorial: Geriatricians, Continuous Quality Improvement, and Improved Care for Older Persons
Morley et al.
J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:M809-812.
FULL TEXT  

Preventable Drug-Drug Interactions: An Ongoing Problem
Journal Watch Cardiology 2003;2003:3-3.
FULL TEXT  

Preventable Drug-Drug Interactions: An Ongoing Problem
JWatch General 2003;2003:1-1.
FULL TEXT