You know that many drugs that are normally considered “safe” when taken alone can cause serious complications when taken with another drug or a supplement. But how about this for a drug-combo complication—sudden death!

You read that right—there are two commonly used drugs that, when taken at the same time, can cause people to simply keel over and die. If you ever get a urinary tract infection, you may be prescribed one of these drugs, a common antibiotic. But if you have heart disease, you might also be taking the other drug—a certain diuretic—in this deadly duo.

Possible result: Cardiac arrest.


The generic name of the diuretic is spironolactone (Aldactone). The danger was recently reported by a Canadian research team that had been investigating ways to prevent a serious side effect of spironolactone—hyperkalemia—caused by the drug’s effect on electrolyte balance and action of reducing potassium loss. Hyperkalemia is the term for having too much potassium in the blood.

In an earlier study, these researchers showed that people who took the antibiotic trimethoprim-sulfamethoxazole—which you may know by the brand names Bactrim and Septra—and spironolactone at the same time were more than 12 times more likely to be admitted to the hospital for hyperkalemia than people who were taking spironolactone and the antibiotic amoxicillin. The reason was not a shocker…trimethoprim can reduce urinary potassium excretion by 40%, increasing the amount of potassium retained in the body, and as mentioned, spironolactone’s potassium-sparing effects can backfire, resulting in accumulation of too much potassium. Taken together, the antibiotic and diuretic can make for a double-whammy of potassium retention.

In their most recent study, the team showed that taking the diuretic and the antibiotic at the same time was associated with an increased risk of sudden cardiac death. Proving this point is crucial because sudden cardiac death is often chalked up to existing heart disease in patients taking spironolactone plus an antibiotic, according to the Canadian researchers, whose work is sponsored by the Canadian Drug Safety and Effectiveness Research Network. Spironolactone, in fact, treats heart failure and high blood pressure by helping the kidneys eliminate excess fluid and sodium from the body, reducing stress on the heart.

Using 17 years’ worth of records from a database that documents drugs prescribed to Ontario residents, the team identified mature adults (66 and older) who were taking spironolactone on a continuous basis. Then, using a different database, the researchers identified which of these adults died of sudden cardiac death within two weeks of being prescribed one of five different antibiotics that treat urinary tract infections—the trimethoprim-sulfamethoxazole and amoxicillin mentioned earlier…plus ciprofloxacin, norfloxacin and nitrofurantoin. Amoxicillin was used as the “control” antibiotic because its chemical make-up, unlike the others, does not interact in any way with that of spironolactone.

To avoid biasing the results, the researchers excluded study subjects who had been prescribed any other antibiotics within 30 days of death, those who had been admitted to the hospital within 30 days of their death and those who did not have a fully functioning immune system.

The results: The rate of sudden cardiac death in patients taking trimethoprim-sulfamethoxazole and spironolactone was nearly 1%–which may sound small but still translates to nearly one out of 100 people taking the combination. That’s a lottery you do not want to win. Because the rate was twice as high as that associated with amoxicillin plus the diuretic, the researchers concluded that risk of sudden death is doubled in people taking trimethoprim-sulfamethoxazole and spironolactone. Ciprofloxacin also was associated with an increased risk compared with amoxicillin, although to a lesser degree, and no risk was associated with the other antibiotics.


Bottom line: We are talking about a meaningful risk of sudden death if trimethoprim-sulfamethoxazole (or ciprofloxacin) is taken with spironolactone. Bringing the potential danger to light better ensures that it can be avoided entirely. If you’re already taking spironolactone and a doctor wants to also prescribe trimethoprim-sulfamethoxazole or ciprofloxacin for any sort of infection—and remember, these are widely prescribed antibiotics—it only makes sense to tell your doctor about the results of this eye-opening study and ask whether an alternative antibiotic not shown to have such a deadly association can treat your infection effectively and safely.