One of our most popular columns is our 'Fact Or Fiction' column, where we investigate certain rumors or misconceptions out there regarding anything pharmacy. In our latest edition, we discuss the whether or not the antibiotic azithromycin is unsafe.

Fact Or Fiction

Is Azithromycin Safe?

The rumor that azithromycin is an unsafe antibiotic choice has been greatly sensationalized. Like all medications, it is associated with possible negative reactions, some of which can be extremely serious. In most cases however, it an appropriate choice in therapy depending on its prescribed use.How did it come about that azithromycin has been deemed dangerous? 

The first thing that should be noted regarding azithromycin is that it belongs to a family of antibiotics known as macrolides. Some other familiar medications in the class you have heard of include erythromycin and clarithromycin.

Macrolides have always been associated with some cardiac risk in patients with certain high risk factors. it was just originally thought that azithromycin may be the exception. The new information about azithromycin simply makes health care professionals consider both the risks and benefits for the macrolide class as a whole.

What Do The Studies Say?

Study 1

A study in the New England Journal of Medicine was published in May of 2012 that compared the cardiovascular risks in patients treated with the commonly used antibiotics amoxicillin, azithromycin, ciprofloxacin, levofloxacin and no medication. The study results showed that there was a small increase in cardiac death among patients on azithromycin as well as patients on levofloxacin.

Based on this study, the FDA added a black box warning to the product information stating that azithromycin is associated with a risk of QT interval prolongation. QT prolongation, for those unfamiliar, can lead to something known as torsades de pointes (TdP), a type of abnormal heart rhythm. In serious cases, it can lead to death. Since this information came out, it raises the question of just how safe azithromycin is to take.

All data points to it being just as safe as other antibiotic classes as long as the patient being treated doesn't have existing risk for QT prolongation, hypokalemia (low potassium), hypomagnesemia (low magnesium) or is currently taking other drugs that have cardiac risks. 

The study in the New England Journal of Medicine did find that levofloxacin (Levaquin) is associated with the same cardiac as azithromycin. Azithromycin seemed to come under more scrutiny based on the volume of prescriptions that have dispensed for patients (over 40 million in 2011). The New England Journal study was NOT a randomized controlled trial proving causation. It was an observational cohort study meaning they simply looked upon and gathered past data from a select group of patients. The following was their selection criteria for who to include in the study.

"Eligible cohort members were 30 to 74 years of age, had no life-threatening noncardiovascular illness, had not received a diagnosis of drug abuse or resided in a nursing home in the previous year, and had not been hospitalized in the prior 30 days".

A current randomized blinded study for azithromycin would never be able to use these parameters and would certainly need to exclude patients with high cardiac risk.

The New England study looked at ALL patients within the age group of 30-74 and did not exclude patients with a known history of cardiac problems, had a high risk for QT prolongation or who were on other medications that could also cause QT prolongation. Now that we know azithromycin can cause problems in those with high cardiac risk, the findings in the study are no surprise.

Azithromycin statsHere we can see the data the was collected during the observational study. The two biggest things that jump out are cumulative incidence of total cardiovascular deaths and  the associated hazard ratio.

They are both significantly higher than patients on either amoxicillin or no antibiotic. We again have to remember that we don't know the  patients current risk factors who were taking these antibiotics. In the discussion portion of the study, the authors make a point of saying the study did not take into account any sort of pre-existing conditions or other lifestyle choices and could have been a significant. actor in the study results.

Clearly, based on this data we would want to find out if the increased incidence in cardiovascular deaths with azithromycin is in fact only because it was being given to the wrong patients who should not have been on it anyway. Fortunately, there are a few studies that investigate this. 

Study 2

A recent study in Journal of Pharmacy Practice published in December of 2013 set out to review and evaluate various medical journals and literature to assess the incidence and clinical relevance of the FDA warning of QT prolongation with azithromycin.

The study found that the literature certainly does point to an increased risk of cardiovascular problems, but is mostly limited to high risk patients, including those who has pre-existing heart conditions and were on other drugs that could cause QT prolongation.

Other Studies

Two additional studies completed in 2013, one published in the New England Journal of Medicine and the other in the Annals of Pharmacotherapy reached the same conclusion that azithromycin can be regarded as safe in patients without risk factors for QT prolongation.

Final Words

The rumor that azithromycin is unsafe depends on the intended treatment population, just like any other drug. While the studies confirming the possible risk of azithromycin have been beneficial to medical providers, it has created much unsubstantiated worry for the public.

As always, prescribers need to be aware of the both the risks and benefits of prescribing a drug and patients should be aware that, without underlying risk of QT prolongation, they should feel safe taking azithromycin.

Result: Questionable