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Combination of popular antibiotic with blood pressure lowering drugs increases risk of sudden death by 40 to 50 per cent


Tens of millions of antibiotic prescriptions are dispensed every year in North America. Among these is co-trimoxazole, an antibiotic commonly used to treat patients with urinary tract infection. Researchers at the Institute for Clinical Evaluative Sciences (ICES) have found that older patients who received co-trimoxazole with an angiotensin converting enzyme-inhibitor (ACE) or an angiotensin receptor blocker (ARB) – popular drugs for the treatment of hypertension, heart disease and diabetes – had a 40 to 50 per cent increase in the short-term risk of sudden death compared to patients receiving the antibiotic amoxicillin.

The combined use of co-trimoxazole with ACE inhibitors or ARBs is a risk factor for high blood potassium levels (hyperkalemia). Severe hyperkalemia can cause fatigue, muscle weakness and sudden death due to an irregular heart rhythm.

“Co-trimoxazole has been around for more than 40 years, but its ability to provoke life-threatening hyperkalemia isn’t as widely appreciated as it deserves to be,” said Dr. David Juurlink, author of the study and scientist at ICES. “These drugs are prescribed together all the time, and yet the risk to patients taking this combination of drugs is very real. For some, it can be fatal,” he added.

The study, published today in the BMJ, is the first to examine whether treatment with co-trimoxazole was associated with a higher risk of sudden death than other antibiotics, used for urinary tract infection in patients receiving ACEs or ARBs.

The population-based study looked at 1,601,542 Ontario residents aged 66 years or older receiving an ACE or ARB between April 1, 1994 and January 1, 2012. The study found 39,879 experienced sudden death; of these, 1,110 occurred within 7 days of a prescription for one of the study antibiotics. The researchers found co-trimoxazole was associated with a 40 to 50 per cent increased risk of sudden death in outpatients receiving ACEs or ARBs. In absolute terms, the researchers estimate that for every 1,000 treated patients, three cases of sudden death will occur within two weeks of co-trimoxazole compared to one case of sudden death following amoxicillin.

“Sudden outpatient death from hyperkalemia is often misattributed to heart disease, particularly in older patients,” noted Juurlink. He added, “Physicians should consider using alternate antibiotics in patients with other risk factors for hyperkalemia when clinically appropriate.”

“Co-trimoxazole and sudden death in patients receiving inhibitors of the renin-angiotensin system: A population-based study,” was published today in the BMJ.

Author block: Michael Fralick, Erin M Macdonald, Tara Gomes, Tony Antoniou, Simon Hollands, Muhammad M Mamdani and David N Juurlink

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy.

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