FDA Warning May Affect How Physicians Prescribe Zithromax
The FDA’s recent warning that the commonly used antibiotic azithromycin (Zithromax) has been associated with a risk of fatal heart rhythms in some patients may lead to changes in physician prescribing habits.
Azithromycin is used to treat acute bacterial exacerbations of chronic pulmonary disease, acute bacterial sinusitis, community-acquired pneumonia, pharyngitis/tonsillitis, uncomplicated skin and skin structure infections, urethritis and cervicitis, and genital ulcer disease.
“The FDA warnings are very sobering for what has been perceived as a very benign medication and should now give clinicians pause before prescribing,” said Stephen Brunton, MD, executive vice president for education at the Primary Care Education Consortium.
The March 12, 2013 warning was based on the agency review of a study published last May in the New England Journal of Medicine and a separate study by the drug’s manufacturer Pfizer.
Azithromycin belongs to the macrolides class of antibacterial drugs. The drug’s labeling has been updated with a stronger Warnings and Precautions section related to the risk of QT interval prolongation and torsades de pointes, a rare heart rhythm abnormality. Individuals at greatest risk include those with existing QT interval prolongation, low blood levels of potassium or magnesium, abnormally slow heart rate, or use of certain drugs known to prolong the QT interval, according to the FDA statement.
In an email to Consultant, Pfizer said that, in collaboration with the FDA, it has updated its drug label. “It is also important to note that the majority of patients treated with Zithromax (azithromycin) are not affected by this label update. This potential risk is well established in macrolide antibiotics, as well as other antibiotics, such as quinolones.”
“I will continue to use these medications when they are indicated, but I will be circumspect,” said Gregory Rutecki, MD, professor of medicine at the University of South Alabama College of Medicine. “First, I will correct other risk factors (e.g., low potassium and magnesium) if present and not use two drugs that prolong the QTc simultaneously. If a patient is already on a QTc prolonging drug, I may avoid adding a second.”
Edward Shahady, MD, clinical professor of family medicine at the University of Miami, said the concern about QT interval is noted with several antibiotics “but with the increased labeling it will change prescribing habits. However, it will take an increased awareness of lab tests and cardiac rhythms.”
The FDA recommends that healthcare professionals consider the risk of fatal heart rhythms associated with azithromycin when treating patients who are already at risk for cardiovascular events. The agency noted that alternative drugs in the macrolide class or non-macrolides also have the potential for QT prolongation or other significant side effects that should be considered when choosing an antibacterial drug.
“Before prescribing any antibiotic a clinician should consider the potential etiology of the infection,” explained Dr. Brunton. “For example, whether it is potentially bacterial and if so what its sensitivities may be.”
In the New England Journal of Medicine study, researchers reviewed the records of Tennessee Medicaid patients prescribed azithromycin between 1992 and 1996 and compared them to individuals treated with amoxicillin, ciprofloxacin, levofloxacin, or no drug. The results showed that during the 5-day course of therapy, patients taking azithromycin had an increased risk of cardiovascular death (hazard ratio [HR], 2.88) and death from any cause (HR, 1.85) compared with those taking no antibiotics.
Furthermore, patients taking azithromycin had an increased risk of cardiovascular death (HR, 2.49) and death from any cause (HR, 2.02) relative to those taking amoxicillin. The risk of cardiovascular death was also significantly higher with azithromycin than with ciprofloxacin, but it was not significantly different when compared with levofloxacin.
The FDA also considered the results of a Pfizer study that assessed the effects of azithromycin on the QT interval. The study results, which have been added to the drug label, indicated that azithromycin prolonged the QTc interval, according to the agency.
“Zithromax (azithromycin) has had a well established benefit risk profile for more than twenty years and continues to be an effective treatment option for patients all over the globe suffering from many types of bacterial infections,” said Pfizer.
The FDA warning may also serve as a reminder to clinicians about the appropriate use of antibiotics. Azithromycin has been used for years primarily to treat respiratory infections. However, it may be overused given that many respiratory infections clear up without antibiotics.
“Antibiotics are overused because patients demand it and have had their demands met in the past. We need more public awareness of the negative aspects of overuse and the natural history of upper respiratory infections [URIs],” said Dr. Shahady.
Dr. Rutecki agreed, “All antibiotics are overused for myriad reasons. URIs are a particular problem in this regard.” He said that research, including a recent study in the Journal of the American Medical Association, has looked at using procalcitonin as a marker for bacterial infections. “When it is not elevated in URIs, symptomatic viral therapy is prescribed without antibiotics.”—Eileen Koutnik-Fotopoulos
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