Margaret A. Hamburg, M.D., Commissioner
Joshua Sharfstein, M.D., Principal Deputy Commissioner
Food and Drug Administration
Department of Health and Human Services
10903 New Hampshire Avenue
Silver Spring, MD, 20993
Dear Drs. Hamburg and Sharfstein,
You both have brought welcome, increased focus and action to protect people from unsafe or possibly unsafe foods. The most recent example is the massive recall last week of products containing hydrolyzed vegetable protein in which the FDA stated that although “no illnesses are known to be associated with this problem of [salmonella bacterial] contamination” the agency was “taking steps to protect the public.”
In contrast to becoming more active and cautious in enhancing food safety by removing potentially dangerous products before they have caused harm, several FDA decisions in the past year regarding prescription drugs can only be described as reckless. By deciding not to ban three drugs in particular, the FDA has endangered the lives and health of hundreds of thousands of people. For each of these drugs there is unequivocal evidence that their dangers, resulting collectively in hundreds of deaths each year, clearly outweigh their health benefits.
This evidence is so clear that two of the drugs – the pain killer propoxyphene (included in Darvocet) and the diet drug sibutramine (Meridia) – have already been removed (propoxyphene) or removal has been recommended (sibutramine) from the market in the U.K. and in Europe. The American and European Diabetes Associations recommended a year ago that the third drug, the diabetes drug Avandia, should not be used. In 2009, there were a total of approximately 23 million prescriptions filled for these three drugs in the U.S.
In deciding to ban propoxyphene in mid-2009, the European Medicines Agency (EMA) stated that “the available evidence suggests that the combination of propoxyphene and acetaminophen [as in Tylenol] is no more effective than acetaminophen on its own” and that “the benefits of all medicines containing propoxyphene, either on its own or in combination, do not outweigh their risks.” An earlier announcement of the eventual ban in the UK has resulted in “a major reduction in deaths involving coproxamol [propoxyphene and acetaminophen] compared with the expected number of deaths (an estimated 295 fewer suicides and 349 fewer deaths including accidental poisonings), but no statistical evidence for an increase in deaths involving either other analgesics or other drugs.” In announcing the UK withdrawal, the government stated: “It has not been possible to identify any patient group in whom the risk-benefit [ratio] may be positive.”
Last year, the FDA ignored the recommendation of one of its own advisory committees to ban propoxyphene, deciding instead to merely increase the warnings. Former FDA Commissioner Dr. Donald Kennedy and former Bureau of Drugs Director Dr. Richard Crout, both at the FDA when it rejected our earlier petition to ban propoxyphene in 1978, now support our petition to ban this drug.
When it recommended the ban of sibutramine in January of this year, the EMA stated that “the benefits of sibutramine-containing medicines do not outweigh their risks,” based on a 10,000 person study showing significantly increased heart attacks, strokes or cardiovascular deaths in people taking the drug compared with those who got a placebo. The FDA, in contrast, said that it had not yet analyzed the data from this same study but will strengthen the drug’s warning label and have an advisory committee meeting in the fall.
A large Canadian study published last year found that for every million people using Avandia instead of a similar but safer diabetes drug, Actos, there would be an excess of 8,300 cases of heart failure and 3,500 excess deaths. Earlier evidence of these needless deaths and other harms were the reason that the American and European Diabetes Associations concluded that “given that other [treatment] options are now recommended, the consensus group members unanimously advised against using rosiglitazone [Avandia].”
Why is it that the FDA is cautious on food safety but reckless on prescription drug safety? The two of you have clearly made a decision to take the lead and insist that the agency does a more public health protective job in the food area. But unfortunately, you have deferred to the existing, dangerously flawed leadership in FDA’s Center for Drug Evaluation and Research (CDER), because you are evidently unwilling to challenge its decisions, including leaving these three dangerous drugs on the market, despite the lack of clear evidence of important health benefits. For foods with possible harm but no evidence yet, there have been recalls, but for these three drugs with the certainty of harm already having been established and other countries acting accordingly for two of them, the FDA seems incapable of protecting the public.
If the agency, under your leadership, is to act on your statements in a June 11, 2009, New England Journal of Medicine article, that the “overriding purpose [of the FDA is] protecting the public health,” and that “some benefits are not worth the risk,” you will insist on the ban of these three drugs, as we have previously petitioned the agency to do. You should also insist on the replacement of the current top drug officials who are responsible for these dangerous decisions with people more intent on protecting the public health, instead of artificially preserving the life of drugs doomed, eventually, to be banned. Until they are banned, you will be complicit, as leaders of the FDA, in the needless, preventable deaths of hundreds or more people a year from drugs with no unique benefits, only unique, life-threatening risks.
If you have further questions about these three drugs or other matters of drug safety or efficacy please contact me and I will be pleased to meet with you.
Sidney M. Wolfe, M.D.
Health Research Group of Public Citizen
cc: Senator Charles Grassley
Representative Henry Waxman
 Hawton K, Bergen H, Simkin S, Brock A, Griffiths C, Romeri E, Smith KL, Kapur N,
Gunnell D. Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales: time series analysis. BMJ 2009;338:b2270.
 Juurlink DN, et al. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. British Medical Journal 2009;339:b2942
 D. M. Nathan & J. B. Buse & M. B. Davidson & E. Ferrannini & R. R. Holman & R. Sherwin & B. Zinman. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care (released electronically 10/22/08)