Drug-drug interactions among elderly patients hospitalized for drug toxicity.
BACKGROUND
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.


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


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


METHODS
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).


METHODS
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.
Juurlink
David N
DN
Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada. david.juurlink@ices.on.ca
Mamdani
Muhammad
M
Kopp
Alexander
A
Laupacis
Andreas
A
Redelmeier
Donald A
DA
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D017291:Clarithromycin / Q000627:therapeutic use; D000075202:Contraindications; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006947:Hyperkalemia / Q000453:epidemiology / Q000209:etiology; D007003:Hypoglycemia / Q000453:epidemiology / Q000209:etiology; D008297:Male; D009864:Ontario / Q000453:epidemiology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D018927:Anti-Asthmatic Agents; D000890:Anti-Infective Agents; D000959:Antihypertensive Agents; D004232:Diuretics; D004077:Digoxin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D017291:Clarithromycin; D005905:Glyburide