Today the FDA released a Safety Announcement to warn the public and health professionals that azithromycin can cause heart abnormalities leading to sudden death. Azithromycin is a macrolide antibiotic, a type of antibiotic already known to be associated with abnormal heart rhythm and an increased risk of sudden death. But azithromycin was widely believed to have minimal toxicity to the heart, because prior studies had not detected the potentially lethal effect. It was that belief that lead it to become widely prescribed, often in elderly patients with heart disease who may be more susceptible to the drug's cardiac effects.
In 2009 JAMA published a study of antibiotic use for acute respiratory tract infections (colds) with Big Data from a national database. The study had encouraging findings of an overall decrease in the use of antibiotics for colds - most caused by viruses which are not treatable with antibiotics. But it also found that even though most antibiotic use decreased, azithromycin use increased substantially, six times between 1995 and 2006. This data shouldn't surprise us. The Z-pack has become so common that patients ask for it by name.
The FDA summary of the data that prompted the warning comes from a NEJM study published in May of 2012 and a manufacturer study that found azithromycin is associated with QT interval prolongation - an irregularity of the heart rhythm that can lead to sudden death.
The NEJM study was a very well designed and conducted large study in a very large population with relatively complete medical record. The NEJM study is a good example of the use of Big Data to examine a
patient safety issue. The study authors used a statewide database to
evaluate the risk after published case reports suggested it. But it was an observational study, a design often disparaged outside the research community. However, well done observational studies are often our best chance at finding harm associated with therapy because, thankfully, harms are relatively rare. Randomized Controlled Trials (RCTs) are often too small or too short in follow-up time to detect increases in harmful side effects. Large observational studies that are carefully planned and carried out to reduce the risks associated with non-experimental design can find these increases.
So we have data that the Z-pac is not as safe as once believed. Data to consider when balancing the benefit and risk to an individual patient. Even when side effects are rare, as they are in this instance, we need to evaluate the seriousness of the side effect, in this case sudden cardiac death. We must balance that risk against the potential benefit from using the drug and assess whether or not the patient needs this specific antibiotic or even any antibiotic.
We have data that while overall antibiotic prescribing for colds is down, prescribing for azithromycin is up, way up. It kills more bacteria and it's easier for patients to complete a full course of therapy. Patients ask for it by name.
And we are concerned about antibiotic resistant bacteria.
Do we need more evidence to Choose Wisely when considering a prescription for antibiotic therapy? The FDA is not saying we should stop using azithromycin. The FDA is warning that our prior belief that it did not share the cardiac toxicity of others in its class was wrong. Dead wrong.
It's time to consider this drug choice more carefully and choose wisely when evaluating antibiotic therapy. Does this patient need azithromycin? Would amoxicillin be effective? Does this patient need an antibiotic at all?
Postscript -Dr. Ireland commented on this issue last year, shortly after the release of the study and the FDA statement.