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Preventable Drug-Drug Interactions: An Ongoing Problem

Common medications for heart disease and diabetes can interact with antibiotics and other agents to cause serious health consequences.

Despite publicity about medical errors, preventable adverse effects of drugs still cause considerable morbidity. In this population-based case-control study, researchers examined the following drug-drug interactions:

• Trimethoprim/sulfamethoxazole (TMP/SMX) inhibition of glyburide metabolism, which increases risk for hypoglycemia;
  
• Clarithromycin inhibition of renal clearance of digoxin, which increases risk for digoxin toxicity; and
  
• Potassium-sparing diuretics in conjunction with angiotensin-converting-enzyme inhibitors, which increases risk for hyperkalemia.
  

Records from 1994 through 2000 were evaluated for all Ontario residents who were 66 or older. Cases were prescribed glyburide, digoxin, or ACE inhibitors and subsequently were hospitalized for hypoglycemia, digoxin toxicity, or hyperkalemia, respectively; controls were age- and sex-matched residents who took the same drugs but were not hospitalized for these adverse events. Glyburide recipients with hypoglycemia were 7 times more likely than controls to have received TMP/SMX during the week before hospitalization. Digoxin recipients with digoxin toxicity were 12 times more likely than controls to have received clarithromycin during the previous week. ACE-inhibitor recipients with hyperkalemia were 20 times more likely than controls to have received potassium-sparing diuretics during the previous week.

Another group also addressed hyperkalemia that was associated with potassium-sparing diuretics. After publication of results from the RALES trial, in which the potassium-sparing diuretic spironolactone reduced mortality after severe heart failure, spironolactone use increased dramatically (Journal Watch Sep 10 1999). Investigators at a Texas hospital examined the incidence of hyperkalemia in 104 heart failure patients who received spironolactone. Serious hyperkalemia developed in 12% of these patients (versus 2% in the RALES trial). Many of these patients received potassium supplements inappropriately, and many should not have received spironolactone because they had renal insufficiency.

Comment: These data remind us to increase our vigilance for drug-drug interactions. However, clinicians cannot possibly remember every potential interaction; indeed, many clinicians aren't even aware of these glyburide and digoxin interactions. Computerized systems are essential for solving this problem.

— Allan S. Brett, MD

Published in Journal Watch General Medicine April 25, 2003

Citation(s):

Juurlink DN et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity. JAMA 2003 Apr 2; 289:1652-8.

• Original article (Subscription may be required)
• Medline abstract (Free)

Bozkurt B et al. Complications of inappropriate use of spironolactone in heart failure: When an old medicine spirals out of new guidelines. J Am Coll Cardiol 2003 Jan 15; 41:211-4.

• Original article (Subscription may be required)
• Medline abstract (Free)