Zithromax: Another prescription drug that fails to justify its existence

By Steven Di Joseph -

At one time, writing about a dangerous prescription drug was an infrequent occurrence. Today, however, it has become difficult to keep up with the negative publicity generated by the seemingly unending list of unsafe drugs. In fact, a review of current online postings from various law firms engaged in pharmaceutical products litigation reveals well over 250 different drugs currently being investigated or actually involved in ongoing litigation.

Amazingly, between 1997 and the end of 2011, in the U.S. alone, 34 prescription drugs as well as numerous over-the-counter medications have been withdrawn from the market. In addition to this large number of outright withdrawals, dozens of other dangerous drugs have managed to stay on the U.S. market only because the Food and Drug Administration (“FDA”) has seen fit to require the manufacturers to include black box (the strongest and most serious) warnings in the drugs’ informational materials. Of course, those warnings, no matter how ominous, often go unheeded by the people taking the drugs much the same way as cigarette-package warnings are regularly ignored. There are also many dangerous drugs that have been withdrawn from the market in other countries (Avandia – withdrawn in Europe) that remain available in the U.S.

Approximately 20% of the prescription drugs that find their way to market have serious side effects that do not show up until long after they are approved. This unenviable record primarily results from two serious flaws in the “fast track” or “accelerated” approval process currently favored by the FDA, namely, the lack of longitudinal (long-term) testing and the use of small test groups that do not represent a true sample of the range of patients likely to take a particular drug.

For this reason, the public watchdog organization, Public Citizen, strongly recommends consumers follow its “Seven Year Rule” by not taking any potentially dangerous prescription drug until it has been safely marketed for 7 years. Most drugs pulled from the market do not even survive for 5 years and some even fail within two years of being approved.

Gradually, the FDA has gone from a guardian of the public’s safety to a conflict-ridden agency that, time after time, acts as little more than a “rubber stamp” for the drug manufacturers by prematurely approving dangerous drugs, failing to enforce post-approval reporting requirements, and delaying (or avoiding) ordering a drug off the market.

One reason the FDA is now viewed in such an anti-consumer light is because it has opted to accept huge sums of money from the pharmaceutical industry to fund the agency’s Approval Division which now favors “fast tracking” drugs to market when that is probably the last thing that should be happening with prescription drugs. Unfortunately, post-approval monitoring of adverse reactions and side effects receives far less funding and has only a fraction of the personnel allocated to the approval process. Fast-track approvals, which are usually based on short-term testing of small test groups, have had disastrous results when used for drugs which are specifically designed for long-term or lifetime use by large segments of the population.

As a result of the “rush-to-market” approach, it is now only a question of “when” and not “if” a suspect drug will fail and, when it does, the failure is, more often then not, catastrophic since it affects the public-at-large and not a small group of test subjects who

Zithromax has now fallen into the category of drugs that, because of over-expanded permissible applications or inadequate post-marketing testing, fall outside of any acceptable risk/benefit analysis. In short, it is being used for too many conditions and by too great a segment of the population. The drug was never intended for such widespread use.

Zithromax (Pfizer) was approved by the FDA in June 1996 for the treatment of Mycobacterium avium complex (MAC) in subjects with advanced HIV infection. At that time, Zithromax was to be taken in a once-weekly 1200 mg dose (two 600 mg tablets). Clinical trials found that “prophylaxis with once-weekly Zithromax reduced the risk of developing MAC bacteria in the bloodstream” as well as the clinical signs and symptoms associated with it.

Of course, even in the early 1990s, when Zithromax was being tested, advanced HIV infection was the precursor to AIDS which is 100% fatal (regardless of how long that takes to occur). Accordingly, the “risk/benefit” analysis was a no-brainer. (Even today, there is no “cure” for HIV/AIDS).

Risk/benefit, in short, is the analytical standard whereby a drug’s potential benefit is weighed against its potential risks. Thus, a drug that effectively treats a 100% fatal disease would be of great benefit and, as a result, a potential risk of 20 deaths per 1,000 users (1/50 or 2%) would be regarded as acceptable. However, a drug that treats toenail fungus but which may prove fatal to one out of every 10,000 users (1/10,000 or .01%) would not be seen as being worth the risk.

Unfortunately, that very logical standard, which was once a critical factor in the decision making process as to whether a drug was approved or not, has been seriously compromised and drugs with comparatively minimal benefits, or designed to treat relatively minor conditions, are frequently approved despite very serious potential risks or side effects.

Zithromax was originally developed as a treatment for people with advanced HIV infection and was shown to be effective in reducing the risk of developing disseminated MAC in two randomized, double-blind trials using people with advanced HIV infection. In fact, in one of the studies, Zithromax was compared to rifabutin as well as to the combination of the two. The finding was that there was a statistically significant difference in favor of Zithromax and the Zithromax-rifabutin combination therapy was more effective than rifabutin alone.

In addition, the “overall” side effects associated with Zithromax were primarily believed to be mild to moderate in nature consisting primarily of diarrhea, nausea, abdominal pain, and loose stools.

However, through the years, Zithromax (and levofloxacin) gradually became accepted as a treatment for a wide range of bacterial infections and by 2010, over 48 million yearly prescriptions for azithromycin and over 9 million for levofloxacin were written. In fact, many of these millions of prescriptions were (and are) written pointlessly for viral (as opposed to bacterial) infections, for which azithromycin, levofloxacin and other antibiotics are of no benefit. Moreover, while azithromycin (and levofloxacin) can be effective in some cases, there are many safer options for the treatment of bacterial infections. Zithromax was even approved for children.

Azithromycin is now used to treat bacterial infections, such as bronchitis, pneumonia, sexually transmitted diseases (STDs), and ear, lung, skin, and throat infections.

As far back as 2001, however, the Zithromax label was updated to include warnings about potential liver damage.  Since Zithromax is a very strong antibiotic and, as with all “macrolides,” is eliminated from the body through the liver, the potential for liver damage and liver failure is significant. The warning states that abnormal liver function, jaundice, necrosis, hepatic failure and death have been reported.

Significantly, Pfizer actually began receiving reports of liver damage associated with Zithromax as early as 1996.  Many of those reports noted the liver damage linked to Zithromax was severe and sometimes fatal.  However, it was not until 2000 (and only after an FDA directive) that Pfizer warned the public about these reports.

On May 17, 2012, the FDA notified healthcare professionals of the study published in the New England Journal Medicine that day (http://www.nejm.org/doi/full/10.1056/NEJMoa1003833) that reported an increase in cardiovascular deaths, and in the risk of death from any cause, in patients treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug. (levofloxacin [LEVAQUIN] was also included in the study report).

The study showed azithromycin to be associated with cardiovascular effects; specifically, prolongation of the QT interval. The study was based on an examination of the medical records of 3.5 million Tennessee Medicaid patients. The analysis showed that those who took azithromycin (commonly dispensed in a five-day “Z-pak”) were almost 300% more likely to die from cardiovascular causes, such as sudden cardiac death, during the five days of therapy than those who took no antibiotics and 250% more likely to die from cardiovascular causes than those who took amoxicillin (AMOXIL). In real numbers, there were 47 to 245 more cardiovascular deaths for every 1 million patients than those who were treated with amoxicillin. The highest risks were in Zithromax patients with existing heart problems.

As a result of the study, many major law firms involved in mass-tort as well as pharmaceutical products litigation have launched their own investigations into whether to pursue claims for damages resulting from injuries associated with Zithromax. Those damages would likely include past and future pain and suffering, wrongful death, medical expenses, lost earnings, medical monitoring, and past and future medical expenses.

Some important lessons to take away from the Zithromax story are: (1) the FDA is not always on the side of the consumer; (2) the pharmaceutical industry is hardly in the business of worrying about the damage done by dangerous prescription drugs as long as profits outpace liability awards and settlements; (3) the longer a drug remains on the market, the more likely it is that it will be granted application to a broader range of conditions as well as to more segments of the general population. (Of course, if the drug turns out to be dangerous or defective, this means that more people will be injured or killed by it); (4) the FDA is more likely to opt for Black Box warnings than it is to order a drug pulled from the market (A close corollary to #1, above); (5) the “Seven Year Rule” is quite sensible and, if followed, would probably prevent a great deal of suffering and death; and (6) drugs, unlike fine wines, do not get better with age. Thus, if they start out with problems, the problems will only get worse, and worse, and worse…

Zithromax side effects can be reported to the FDA’s MedWatch Adverse Event Reporting program at http://www.fda.gov/Safety/MedWatch or 1-800-332-1088.

Diseases, Drugs, General

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