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Posted on 09.13.04
Popular Antibiotic Raises Risk of Cardiac Arrest Five Fold
By Martha C. Rundles
According to a new CERTs study, erythromycin, an antibiotic prescribed to treat everything from strep throat to gonorrhea, increases the chances of sudden cardiac death five fold when used in combination with several common drugs prescribed for infections and high blood pressure. The study, which appears in the September 9 issue of the New England Journal of Medicine, was conducted by the Vanderbilt University Medical Center CERTs center.
“The new study shows the need for continued research on the safety of older medicines, including looking at how they interact with newer drugs,” said Dr. Wayne A. Ray, principal investigator at the Vanderbilt center and lead author on the paper.
Erythromycin is a widely used, inexpensive drug that has been on the market for 50 years and thought to be relatively innocuous. However, there have been case reports of patients experiencing cardiac arrest when using the antibiotic orally and intravenously. For example, the once popular allergy drug Seldane was pulled from the market in 1998 after reports of sudden cardiac death were linked with concurrent use of erythromycin.
Until now, the magnitude of the risk had not been fully addressed in a quantified study. To examine the issue, the team of researchers studied medical records of 4,404 patients enrolled in the Tennessee Medicaid program, known as TennCare, from 1988 to 1993, who died of cardiac arrest. They reviewed prescriptions for erythromycin, amoxicillin, and other medications from computerized Medicaid pharmacy files that included drug, dose, and total medication dispensed.
Many of the medications at risk when combined with erythromycin are those newer drugs to which Dr. Ray referred, and some of them inhibit a specific type of drug enzyme known as cytochrome P450 3A (CYP3A). These CYP3A inhibitors slow down the erythromycin's breakdown, thereby increasing its concentration in the bloodstream. This process can trigger an abnormal, potentially fatal heart rhythm.
Three patients from the study had died of cardiac arrest when combining erythromycin with blood pressure drugs: verapamil (Calan, Isoptin, and Verelan) and diltiazem (Cardizem and Tiazac).
Other specific drugs that pose a risk in combined form are the antibiotic clariothromycin (Biaxin); antidepressant Nefazodone (Serzone); and certain anti-fungal drugs, such as fluconazole (Difucan), ketoconazole (Nizoral), and itraconazole (Sporanox). Among this group, only pills and injections carry risk, and topical forms do not.
Also, the AIDS/HIV drugs known as protease inhibitors should be avoided, as well as grapefruit juice, which is a recognized catalyst of drug interactions.
Also important is that researchers did not find the same increased risk of cardiac arrest with other commonly prescribed antibiotics, such as amoxicillin, or for those patients who had taken erythromycin in the past.
“This study provides critical scientific evidence that can be used to improve health care quality and safety by preventing potentially dangerous drug interactions,” said Agency for Healthcare Research and Quality Director Carolyn M. Clancey. “These findings will help clinicians to make more informed choices about which antibiotics should be used with patients who are taking multiple medications.”
With safer alternatives, such as amoxicillin, readily available, researchers from the study conclude that clinicians should avoid prescribing a combination of erythromycin and CYP3A inhibitors concurrently.
Funding for this Vanderbilt CERTs center study was provided by grants from the Agency for Healthcare Research and Quality.
Joining Dr. Ray were Katherine T. Murray, M.D., Sarah Meredith, M.B., B.S., Sukumar Suguna Narasimhulu, M.B., B.S., M.P.H., Kathi Hall, M.S., and C. Michael Stein, M.B., Ch.B.