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AZITHROMYCIN WARNINGS GET STRONGER AFTER 19 YEARS


The FDA issued a warning on March 12, 2003 regarding the antibacterial drug, azithromycin. Also known as Zithromax or Zmax, azithromycin was approved to treat acute bacterial infections. Most commonly it is prescribed to treat acute bacterial sinusitis and community-acquired pneumonia, pharyngitis and tonsillitis.

The March 12, 2003 warning was about an increased risk of abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. However, it was just on May 17, 2012 that the FDA released a statement about a study that reported an increase in cardiovascular deaths and death from any cause in persons treated with a 5-day course of azithromycin. The FDA recommended at that time that health care professionals should consider this increased risk when prescribing azithromycin for patients already at risk for cardiovascular events.

It was a medical/scientific study published in the respected New England Journal of Medicine that led to the FDA’s May 17, 2012 statement. That study compared the risks of cardiovascular death in patients treated with azithromycin (Zithromax), amoxicillin, ciprofloxacin (Cipro), levofloxacin (Levaquin), and no antibacterial drug, and found what the FDA reported was a small increase in cardiovascular deaths.

The FDA also points out in its 2012 statement that in 2011, the FDA reviewed macrolide drug labeling information related to these very risks. That review resulted in the WARNINGS AND PRECAUTIONS section of the Zmax drug label being revised in March 2012 to include new information regarding risk for QT interval prolongation, still referring to the risk as low. So one year later, the FDA was able to conclude that the risk is low, not small.

So in 2011, the FDA determined the risk was small, in 2012 the FDA determined that same risk to be low, and in 2013 the FDA deletes these downplay of the risk and warns that azithromycin can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. However, this hide the ball game has been going on much longer than that.

The first azithromycin drug, Zithromax, was approved in September 1994, and in that first label through the October 2007 label, it had a very weak warning about this very serious side effect:

There has been a spontaneous report from the post-marketing experience of a patient with previous history of arrhythmias who experienced torsades de pointes and subsequent myocardial infarction following a course of azithromycin therapy. (Emphasis added.)

In 2010 and thereafter the warning mirrored that of Zmax (below).

The second azithromycin drug, Zmax, was approved in 2005, and its first and subsequent labels changes in August 2007, September 2008, and October 2010, list adverse reactions in post-marketing reports to include:

Cardiovascular: palpitations and arrhythmias including ventricular tachycardia and hypotension. There have been rare reports of QT prolongation and torsades de pointes.

It was not until the 2011 Zmax label that this warning was strengthened in content and placement, now appearing fifth in order of severity in the Warnings and Precautions section of the label:

Prolongation of the QT interval and cases of torsades de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval. (5.5)

Doing its best to downplay the risk in the March, 2012 label, Zmax manufacturer Pfizer stated the following:

Although the absolute risk is unknown, it appears to be low with azithromycin likely due to the lack of appreciable drug interactions, and the observation that it is rarely reported as a post-marketing adverse event. (Emphasis added.)

In conclusion, it is evident from 1994 that Pfizer knew that its azithromycin could cause Prolongation of the QT interval and cases of torsades de pointes, both serious conditions that can result in death. The FDA knew this too because it approved the content of the original label and every change thereto. Yet, over the next 17 years, the FDA believed Pfizer’s representations that the risk was small and low, even though very serious. Then, after the FDA’s review of the New England Journal of Medicine study, it determined that the risk was greater than that and required strengthened warnings in 2012 and 2013.

The problem is that patients, their doctors, and the FDA are totally dependent upon the drug companies to provide accurate and complete information and warnings about the serious risks of their drugs. Remember, the FDA does not do its own testing or studies about the drugs it approves. The FDA gets its information from the drug company, and until it gets information from an independent source, such as a study published in a respected medical journal such as the New England Journal of Medicine, it knows no different. Further, the drug company is charged with the responsibility of collecting and reporting to the FDA all after-market reports of adverse events from their drugs.

Where is the drug companies motivation to provide accurate and complete information when billions of dollars are at stake? With the fox guarding the hen house, it is more likely than not that the drug companies pro