Prescription for Disaster: The Dirty Dozen FDA-Approved Pharmaceutical Drugs

By Gary Null, PhD and Jeremy Stillman

The Food and Drug Administration is mandated with the responsibility to ensure that our foods and medications are safe and effective. Hence, when a physician, primary health care provider or pharmacist provides a consumer with these medications, there is a fundamental belief that these work and will do minimal harm. Then we meet reality. The FDA has not only allowed extraordinarily inefficient, extremely toxic drugs onto the market, but then has ran interference on behalf of pharmaceutical companies and other special interests to protect their profits instead of immediately withdrawing their drugs from the market.

The consequence of eating at a restaurant you dont like is that you wont go back again. The consequence of taking a toxic drug is injury or death. The FDA has a long history of allowing deadly drugs to be promoted and marketed. The FDA has not sought prosecution when prima facie evidence proves that the manufacturers and their scientists, boards of directors and marketers knew all along that these drugs did not work as claimed or had dangerous side effects that they withheld from the FDA . These companies have engaged in overtly criminal activities and instead of ending up in prison or bankrupt, no one is held accountable. Bonuses are given and the value of their corporate holdings goes up- its all part of the cost of doing business today. This article is to show you clear and exact examples of lethal and harmful drugs that should never have been marketed some of which are still available to consumers. They are drugs that an honest and diligent FDA would never have allowed to be released on the market. Cumulatively, tens of

thousands of Americans have died and hundreds of thousands more have been injured. And the standard penalty meted out for such criminality? Pay a fine. Smile. You got out of jail free.

Fen-Phen (fenfluramine/dexfenfluramine/phentermine)

The fen-phen diet drug cocktail was popularized in the mid 1990s as Americans rushed to take pills that were heralded by Time Magazine as a new miracle drug.1 The new pill was known as Redux and was a slightly modified version of Pondimim, a diet drug that had been on the market since 1974.2 Both Redux and Pondimim were to be used in combination with the phentermine, an amphetamine-like stimulant. The drug was manufactured by American Home Products which changed its name to Wyeth-Ayerst in 2002, and was later taken over by Pfizer in 2009. The active ingredient in these diet pills were fenfluramine and dexfenfluramine - drugs that falls into the class of selective serotonin re-uptake inhibitors (SSRI). 3 These drugs increase levels of serotonin released in the body - a process that the drugs maker claimed would induce feelings of satiety and promote weight loss. In 1996 alone, over 18 million prescriptions for Redux were handed out by physicians.4

In the summer of 1997, an article appeared in the New England Journal of Medicine by researchers at the Mayo Clinic which linked fen-phen with primary pulmonary hypertension (PPH), a debilitating and incurable heart valve condition that is often fatal. The report profiled a 29 year old
1

Cohen, Kate. "The Fda - Fen Phen Nation | Dangerous Prescription | FRONTLINE | PBS." PBS: Public Broadcasting Service. http://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/fenphen.html (accessed October 21, 2011).
2 3 4

Ibid

"Interviews - Leo Lutwak, M.d. | Dangerous Prescription | FRONTLINE | PBS." PBS: Public Broadcasting Service. http://www.pbs.org/wgbh/pages/frontline/shows/prescription/interviews/lutwak.html (accessed October 21, 2011).

I Cohen, Kate. "The Fda - Fen Phen Nation | Dangerous Prescription | FRONTLINE | PBS." PBS: Public Broadcasting Service. http://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/fenphen.html (accessed October 21, 2011).

woman who died from PPH just 23 days after taking fen-phen.5 In response to this paper and dozens of reports to the FDA connecting fen-phen with serious cardiovascular problems, both Redux and Pondimim were recalled on Setpember 15, 1997. American Home Products had profited over $200 million dollars in the short time that Redux and Pondimum were on the market. 6

The dangerous side effects associated with taking this drug had been established before it was approved in April 1996. Months before approving the drug, a letter to FDA officials from watchdog group Public Citizen noted scientific studies linking dexfenfluramine with neurological damage and a nine-fold increase in the risk of primary pulmonary hypertension. The Public Citizen letter also cited clinical trials which concluded that the drug was largely ineffective in fighting obesity.
7

According to Debbie Danowski and Peter Lazaros book Why Cant I Stop Eating: Recognizing, Undertstanding and Overcoming Food Addiction, medical studies have shown the risk of developing PPH while taking fen/phen to be over 30 times greater. The book also points out that the difficulty in diagnosing PPH in connection with these drugs- it could happen that a persons only symptoms will be shortness of breath and then death. 8

The gross negligence on the part of FDA in approving this drug was made clear during a PBS interview with Dr. Stuart Rich, a consultant to FDA during the approval of Redux who now serves as the president of the Pulmonary Vascular Research Institute . Rich expressed his disbelief over
5

Brody, Jane E.. "Archive: Personal Health: Obesity drugs: Weighing the risks to health against the small victories.." The New York Times . http://www.nytimes.com/specials/women/warchive/970903_1241.html (accessed October 21, 2011).
6

Cohen, Kate. "The Fda - Fen Phen Nation | Dangerous Prescription | FRONTLINE | PBS." PBS: Public Broadcasting Service. http://www.pbs.org/wgbh/pages/frontline/shows/prescription/hazard/fenphen.html (accessed October 21, 2011).
7 8

Public Citizen. "Letter to FDA." Citizen.org. www.citizen.org/documents/1389.pdf (accessed October 17, 2011).

Danowski, Debbie , and Pedro Lazaro, M.D.. Why Can't I Stop Eating?: Recognizing, Understanding, and Overcoming Food Addiction. Center City: Hazelden, 2000. Print.

the FDA pushing fen-phen given the drugs known serious effects on cardiovascular health and marginal efficacy. Rich also explained that he was invited to testify with other experts before an FDA drug approval committee on the safety and efficacy of Redux at a meeting that took place in September 1995. During the meeting, the committee decided not to approve Redux on the grounds that it was unsafe. However, before the final vote was cast, FDA division head James Bilstad unexpectedly interrupted the proceedings and postponed the vote for another time. According to Rich, none of the experts who previously testified were invited back to the next meeting which ultimately resulted in the drug being approved in a 6-5 vote.9

After the approval of Redux, Dr. Rich appeared on the Today Show where he advised that the drug be prescribed with utmost caution by physicians due to its potentially damaging side effects and only in cases where obesity was a life-threatening problem. Rich explained to PBS that shortly after his television appearance he received a phone call by an executive from drug maker American Home Products. The doctor was told by the AHP representative in no uncertain terms that bad things would happen if he continued to speak to the media about the weight loss medication.10

All told, American Home Products /Wyeth Ayerst has paid out over $14 billion to more than 200,000 fen-phen victims in legal settlements.11 An estimate on how many deaths can be attributed to taking fen-phen is still the subject of debate but almost certainly numbers in the thousands.

Vioxx (Rofecoxib)

"Interviews - Stuart Rich, M.d. | Dangerous Prescription | FRONTLINE | PBS." PBS: Public Broadcasting Service. http://www.pbs.org/wgbh/pages/frontline/shows/prescription/interviews/rich.html (accessed October 16, 2011).
10 11

Ibid

"The Fen-Phen Follies." American Lawyer, March 1, 2005. http://www.law.com/jsp/tal/PubArticleTAL.jsp? id=900005424104&slreturn=1 (accessed October 19, 2011).

The recall of Mercks Vioxx stands as one of the largest drug recalls in history. Despite internal studies associating the drug with serious cardiovascular side effects before it came on the market, the FDA approved Vioxx in 1999 to be used as a painkiller to treat conditions such as arthritis and menstrual pain. Vioxx falls into the class of non-steroidal anti-inflammatory drugs (NSAID). Over the next four and a half years, 100 million prescriptions for Vioxx were handed out as Merck would rake in $2.5 billion a year in worldwide sales.12 All the while, thousands were dropping dead from heart attacks induced by their drug.

One of the most outspoken critics of Vioxx has been Dr. David Graham, a physician who worked for over 20 years with the FDA. He received degrees in from Johns Hopkins University Medical School and trained at Yale and UPenn. In 2004, while holding the position of Associate Director for Science and Medicine in the FDAs Office of Drug Safety, he testified before Congress about serious dangers associated with Vioxx that were ignored by FDA officials before it was approved and expressed his conviction that harmful and dangerous drugs would continue to be released on the market under the FDAs dubious drug review process. 13 Graham also noted that studies carried out by drug manufacturer Merck before Vioxx was approved indicated that taking Vioxx would increase the risk of heart attack by five to seven times. 14

According to Shannon Brownlees book Overtreated: Why Too Much Medicine Is Making Us Sicker and Poorer, a comprehensive study conducted by Merck that was released in 2000 confirmed previous studies on Vioxx linking it with an increased risk of cardiac arrest and stroke. Brownlee
12 13 14

Nesi, Thomas J.. Poison pills: the untold story of the Vioxx drug scandal. New York: Thomas Dunne Books, 2008.

"Testimony of David J. Graham, MD, MPH, November 18, 2004." finance.senate.gov. finance.senate.gov/imo/media/doc/111804dgtest.pdf (accessed October 18, 2011).

Ibid

writes that instead of pulling the drug off the shelves, the FDA spent 18 months discussing with Merck how to word the warning that was to be placed on the label. By the time the warning did appear on the label, it was so benign-sounding that it had very little effect on sales. 15

In a 3 year epidemiological study released in August 2004, Dr. Graham and his team uncovered that taking a low-dose of Vioxx increased the risk of heart attack and sudden death nearly twofold while a high-dose amount would increase that risk by 3.7.16 With such clear evidence of a heart attack risk, Graham advised that Vioxx not be prescribed or taken by patients. On election day of that same year, the FDA quietly posted to their website a report based on Grahams study which purported that Vioxx was responsible for an estimated 28,000 excess cases of heart attack or sudden cardiac death. Graham contends that this is an underestimation and that it is more likely that the sum lies between 88,000 to 139,000 and that 30%-40% of those individuals died while others sustained life-altering damage to their health. 17

Graham intended on presenting his disturbing findings at the International Conference on Pharmacoepidemiology in France. However, upon learning of his plans, directors within the FDAs Office of New Drugs and the Office of Drug Safety attempted to dissuade him sharing his conclusions unless they were significantly altered. Graham was shocked at how unresponsive management at the FDA was to these alarming revelations with one director going so far as to suggest that Graham should change his conclusions because the FDA wasnt contemplating placing a warning on high-dose Vioxx. 18
15 16 17 18

Brownlee, Shannon. Overtreated: why too much medicine is making us sicker and poorer. London: Bloomsbury, 2007. Testimony of David J. Graham, MD, MPH, November 18, 2004." finance.senate.gov. finance.senate.gov/imo/media/doc/111804dgtest.pdf (accessed October 18, 2011).

Ibid Ibid

Graham also spoke before Congress of the dangerous culture of non-disclosure and resistance that exists within FDA offices, particularly the Office of Drug Safety and the Office of New Drugs, where numerous cases of risky drugs were approved without taking into consideration serious health concerns and other risky drugs were kept on the market despite indications they were unsafe.19

It was only after numerous other studies had been published connecting Vioxx with heart attacks and strokes that it was recalled 2004.20 Lawsuits stemming from the Vioxx scandal have obligated Merck to pay out nearly $5 billion in compensation to victims in the United States.21

Rezulin (Troglitazone)

Warner-Lambert (which was later acquired by Pfizer in 2000) was the manufacturer of the diabetes drug Rezulin. The drug was approved in January 1997 and within a matter of months, dozens of hospitalizations due to liver toxicity in connection with Rezulin were being reported to the FDA. Despite the dangers of the drug becoming manifest, agency officials remained supportive of the drug . The agency was slow to take any action besides adding a warning on Rezulins label explaining that patients taking the medication should have frequent tests evaluating their liverfunction.

19 20 21

Ibid

Brownlee, Shannon. Overtreated: why too much medicine is making us sicker and poorer. London: Bloomsbury, 2007. Goldstein, Jacob. "Merck Vioxx Litigation: Settlements and Pending Cases - Health Blog - WSJ." WSJ Blogs - WSJ. http://blogs.wsj.com/health/2010/02/10/vioxx-lawsuits-whats-been-settled-whats-still-going/ (accessed October 21, 2011).

The toxic effect of Rezulin on the liver had been proven in tests before the drug was given the green light by the FDA. During the review process, concerns over the drug were raised by agency officer Dr. John L. Gueriguian who showed that Rezulin was harmful to the the liver and heart and accordingly should not be approved. Before the drug was approved, Warner-Lambert relieved Gueriguian of his role reviewing the new medication and none of his work documenting the dangers was submitted for the final review. 22 In his testimony before Congress, Dr. David Graham asserted that when it came to Rezulin, the FDAs Center for Drug Evaluation and Research relied on risk management strategies that were utterly ineffective and it persisted in relying on these strategies long after the evidence was clear that they didnt work.23 Dr. Robert Misbin one of the FDAs medical reviewers, voiced his misgivings over the drug as the death toll rose by the hundreds before the drug was recalled in 2000. Misbin was subject to intimidation and threats of being fired by FDA superiors after he submitted internal e-mail correspondences to colleagues which detailed his concerns over Rezulin to Congress. 2425

Even though official estimates place the number of deaths from Rezulin at fewer than 100, some suspect that that figure could be 4 times higher.26 As of 2009, both state and federal

22

Willman, David. "REZULIN: Fast-Track Approval and a Slow Withdrawal - latimes.com." Los Angeles Times California, national and world news - latimes.com. http://www.latimes.com/news/nationworld/nation/la122001rezulin,0,4831559.story (accessed October 21, 2011).
23

"Testimony of David J. Graham, MD, MPH, November 18, 2004." finance.senate.gov. finance.senate.gov/imo/media/doc/111804dgtest.pdf (accessed October 18, 2011).
24

Willman, David. "REZULIN: Fast-Track Approval and a Slow Withdrawal - latimes.com." Los Angeles Times California, national and world news - latimes.com. http://www.latimes.com/news/nationworld/nation/la122001rezulin,0,4831559.story (accessed October 21, 2011).
25 26

Willman, David. " The Pulitzer Prizes | Physician Who Opposes Rezulin Is Threatened by FDA With Dismissal ." The Pulitzer Prizes . http://www.pulitzer.org/archives/6484 (accessed October 21, 2011). "Drug Recalls - Rezulin Linked to Liver Failure & Heart Disease." Drug Recalls . http://www.drugrecalls.com/rezulin.html (accessed October 21, 2011).

courts have required Pfizer to compensate most of the 35,000 personal injury claims have been filed by Rezulin users. The pay outs have totaled around $750 million.27

Avandia (Rosiglitazone):

Originally marketed as a safer diabetes medication in the wake of the controversy over Rezulin, the drug Avandia has generated one of the largest scandals in the history of pharmaceuticals. Before and after the approval of the drug in 1999, numerous tests determined that Avandia was dangerous to heart health. A study undertook by manufacturer SmithKline Beecham (which after merge in 2000, became GlaxoSmithKline) shortly before the drug was approved, concluded that patients taking Avandia were at a significantly higher risk of experiencing heart problems compared to individuals taking Actos, another competing drug.28 Not until 2010 were the results of this study made public in an investigation by the New York Times.

A deposition reported on by the publication documented Avandia's deleterious effects on cardiovascular health and provided a glimpse into the cozy relationship between the FDA and leadership of GlaxoSmith Beecham. Unearthed in the deposition was an inter-office email message in which a director at GlaxoSmith Beecham expresses his hopefulness that Dr. John Jenkins, the head of the FDA's office of new drugs, would facilitate the drug's approval process despite its dangers. The director wrote in his message that it is clear the office of new drugs is trying to find minimal language that will satisfy the office of drug safety.29
27 28

Feeley, Jef. "Pfizer Ends Rezulin Cases With $205 Million to Spare (Update1) - Bloomberg." Bloomberg . http://www.bloomberg.com/apps/news?pid=newsarchive&sid=act0akCefQwo (accessed October 21, 2011). Harris, Gardiner. "Diabetes Drug Maker Hid Test Data, Files Indicate - NYTimes.com." The New York Times . http://www.nytimes.com/2010/07/13/health/policy/13avandia.html? adxnnl=1&ref=avandiadrug&adxnnlx=1319223846-h0flJ11Cg/QhDShZ5ZTTPg# (accessed October 21, 2011).
29

Ibid

The NYT also profiled a supervisor who was employed by the FDA's drug safety office, Dr. Rosemary Johann-Liang. After recommending that Avandia's warning label be more stronglyworded, Dr. Johann-Liang was admonished by agency officials and resigned from her position soon thereafter. Commenting on the apparent conflict of interest between Jenkins and the company she stated that this should not happen.30

A Time Magazine investigation revealed that in 2007, GlaxoSmithKline representatives successfully lobbied the FDA to keep Avandia (which had netted the company $3.2 billion the previous year) on the market despite the companys internal studies which demonstrated that the drug increased the risk of heart attack by 46%. That same year, a study published in the New England Journal of Medicine concluded that Avandia users were 43% more likely to have heart attacks than the general population.31 This corroborated the findings of another independent study linking the drug with myocardial ischemia in 2007 carried out by researchers at the Cleveland Clinic.32

One study referenced in a New York Times article estimated that from 1999-2009, more than 47,000 people taking Avandia needlessly suffered a heart attack, stroke or heart failure, or died. 33 After an investigation of Avandia, members of the Senate Finance Committee criticized the FDA

30 31 32 33

Ibid

Calabresi, Massimo. "Avandia Approval: FDA's Drug-Safety Protection in Doubt - TIME." TIME.com. http://www.time.com/time/magazine/article/0,9171,2010181-2,00.html (accessed October 21, 2011). Ibid Harris, Gardiner. "F.D.A. to Severely Restrict Diabetes Drug Avandia - NYTimes.com." The New York Times. http://www.nytimes.com/2010/09/24/health/policy/24avandia.html?pagewanted=all (accessed October 21, 2011).

for failing to act as 83,000 reports of serious adverse events directly related to taking Avandia flooded the agencys offices from 1999-2007.34

Incredibly, Avandia has still not been fully recalled. In the fall of 2010, FDA officials placed heavy restrictions on the drug only if patients can prove they have tried every other anti-diabetes drug and are aware of the risks involved can they be prescribed the medication. 35

In a mega-settlement involving over 10,000 victims seeking compensation from GlaxoSmithKline for Avandia-related injury in 2010, the company agreed to pay $460 million. This comes on the heels of the first round of Avandia lawsuits which obligated GlaxoSmithKline to pay around $60 million. About 3,000 additional cases are still waiting to be decided on.

Celebrex (celecoxib)

Originally manufactured by Pharmacia (which was taken over by Pfizer in 2002) Celebrex was approved in late 1998 by the FDA and like Vioxx and Bextra, is a special type of non-steroidal antiinflammatory drug (NSAID) known as a COX-2 inhibitor. Touted as a new wonder drug to help patients suffering from rheumatoid arthritis and osteoarthritis more effectively and with fewer side effects than other medications, Celebrex was soon shown to have serious effects on cardiovascular health. Just 3 months after Celebrex was being prescribed, the Wall Street Journal reported on 10 deaths related to the drug.36
34

Emord, Jonathan. "Clear Case of Big Pharmas Hold on FDA: Agency Ignored Dangers of Diabetes Drug Avandia | Health Freedom Alliance." Health Freedom Alliance. http://healthfreedoms.org/2011/01/12/clear-case-of-big-pharmashold-on-fda-agency-ignored-dangers-of-diabetes-drug-avandia/ (accessed October 21, 2011).
35

"Avandia (Drug) - Health - The New York Times." Times Topics - The New York Times. http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/avandiadrug/index.html? scp=1&sq=rezulin&st=cse (accessed October 21, 2011).
36

" Searle Responds to Journal Report On Celebrex Side Effects." P\S\L Group. http://www.pslgroup.com/dg/f8f2e.htm (accessed October 14, 2011).

Celebrex was marketed as an alternative to traditional NSAIDs such as ibuprofen that had been known to cause gastrointestinal side effects. This claim was later found to be untrue when a Health Canada study in 2002 showed that, in fact, Celebrex was not less damaging to the stomach than either ibuprofen or another NSAID, Voltaren. In less than two years on the market in Canada, health authorities had already received 70 reports of gastrointestinal bleeding related to the medication.37

In 2005, Pfizer admitted that an internal study from 1999 on the elderly showed that Celebrex posed a serious risk to heart health. The results of this study which were disclosed to the FDA in 2001 revealed that, compared to the placebo group, individuals taking Celebrex were nearly 4 times as likely to experience a heart attack. 38 An additional study appearing in the New England Journal of Medicine documented that taking the prescribed 400mg dose of celecoxib resulted in a 3.4 fold increase in cardiovascular-related death, myocardial infarctions or stroke. Among those taking the 200mg dose, the risk was 2.5 times greater. 39 In light of these findings, Pfizer agreed to withdraw public advertisements for Celebrex in 2004- still, the pharmaceutical giant continues to manufacture the pills and enjoys the full approval of the FDA.40

Bextra (valdecoxib)

37 38

"Vioxx, Celebrex: Concerns over popular arthritis drugs." CBC. http://www.cbc.ca/news/background/drugs/cox2.html (accessed October 19, 2011). Berenson, Alex, and Gardiner Harris. " Pfizer Says 1999 Trials Revealed Risks With Celebrex." The New York Times . http://www.nytimes.com/2005/02/01/business/01drug.html?adxnnl=1&adxnnlx=1319464929du17+q0mWBTaw02euxZRqA (accessed October 18, 2011).
39

Solomon, Scott D et al "Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention." New England Journal of Medicine 325: 1071-1080 (2005). http://www.nejm.org/doi/full/10.1056/NEJMoa050405#t=abstract (accessed October 18, 2011)
40

Berenson, Alex. "Pfizer to Halt Its Advertising of Celebrex to Consumers." The New York Times . http://www.nytimes.com/2004/12/19/business/19cnd-cele.html (accessed October 24, 2011).

Bextra was approved by the FDA in 2001 to treat arthritis; at the time of approval the agency turned down a bid from the drugs maker, Pharmacia ( later taken over by Pfizer in 2002), to approve Bextra for patients dealing with acute pain after surgery. According to Melody Petersens book Our Daily Meds, the FDA did not disclose to the public that they did not approve the drug for postsurgical pain. The reason for this was concealed in secret agency documents which discussed a clinical trial of Bextra being used on patients undergoing heart bypass surgery. In the trial, patients were shown to have an excess of serious adverse events, including death. These confidential documents also established that Bextra, despite claims by the manufacturer, was shown to be no more effective at alleviating pain than lower-priced painkillers such as naproxen and ibuprofen. 41

In an interview with the New York Times in 2004, Dr. Garret FitzGerald, a cardiologist and pharmacologist at UPenn and a leading expert in COX-2 drugs, expressed his concerns over the dangers of Bextra saying the drug was a time bomb waiting to go off that appeared even more deadly than Vioxx. 42 He drew his assertions in part on a study of 12 clinical trials whose results were presented at a meeting of the American Heart Association; the study concluded that patients taking Bextra were more than twice as likely to suffer heart attacks and strokes. One of the studys authors interviewed by the newspaper was Dr. Curt Furberg of Wake Forest Universitys School of Medicine. Furberg stated that we showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information. 43

41 42 43

Petersen, Melody. Our daily meds: how the pharmaceutical companies transformed themselves into slick marketing machines and hooked the nation on prescription drugs. New York: Farrar, Straus and Giroux, 2008. Harris, Gardiner. "New Study Links Pfizer's Bextra, Similar to Vioxx, to Heart Attacks." The New York Times. http://www.nytimes.com/2004/11/10/business/10drug.html (accessed October 13, 2011). Ibid

Further, Bextra was never shown to decrease cases of adverse events related to gastrointestinal health.44 Bextra was finally removed from the market in 2005 when the FDA asked Pfizer to carry out a voluntary withdrawal of the drug as evidence piled up linking Bextra with heart attack, stroke as well as acute skin conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
45

This request for voluntary withdrawal came less than 2 months after the FDA Panel Advisory

Panel recommended the drug remain available to consumers. 46

In February 2005, Senate Finance Committee Chairman Charles Grassley blasted FDA authorities over the apparent conflict of interest between Big-Pharma and members of the regulatory panels that voted in favor of keeping both Bextra and Vioxx on the market. Grassley pointed out that 10 members sitting on the 32-person advisory board had worked as consultants or had otherwise been employed by Pfizer.47 In the cases of Bextra and Vioxx, these 10 people voted in favor of the drugs remaining available to consumers. The Center for Science in the Public Interest noted that nearly all of the panel members charged with making these life-altering decisions had ties to other pharmaceutical corporations.48

In a 2008 settlement, Pfizer agreed to settle nearly all the injury cases related to Celebrex and Bextra in an $894 million settlement with about 7,000 parties.49 In addition to personal damages, in 2009, Pfizer was mandated by the Justice Department to pay $2.3 billion for an off-label, illegal
44 45

Ibid

Fields, Theodore et al "Bextra Withdrawal from the Market - HSS Physicians Reflect on Options for Patients in Pain - HSS.edu - HSS." Hospital for Special Surgery. http://www.hss.edu/conditions_bextra-withdrawal-hss-physiciansreflect-options.asp (accessed October 24, 2011).
46 47

Ibid

Alonso-Zaldivar, Ricardo. "Senator Questions FDA Panelists' Ties to Industry - latimes.com." Los Angeles Times . http://www.latimes.com/news/nationworld/washingtondc/la-na-fda26feb26,0,7305839.story (accessed October 24, 2011).
48 49

Ibid

Johnson, Linda A.. "Pfizer Reaches Massive Settlement In Celebrex, Bextra Lawsuits." The Huffington Post. http://www.huffingtonpost.com/2008/10/17/pfizer-reaches-massive-se_n_135518.html (accessed October 21, 2011).

campaign that advertised Bextra and several other drugs. Pfizer was charged with making claims that the medication could be used as a substitute for drugs like morphine for patients dealing with pain after surgery. 50 One Pfizer executive, Mary Holloway, who helped spearhead the illegal campaign, was fined $75,000 and given two years probation. Another sales manager at the company involved in the scandal was Thomas Farina who was ordered to serve a 6 month sentence of home confinement.51

Baycol (Cerivastatin)

Baycol was approved by the FDA in 1997 as a cholesterol-lowering statin drug.

The drug was

manufactured by German company Bayer which teamed up with SmithKline Beecham (later became GlaxoSmithKline) to market the drug. Baycol quickly drew criticism for its potentially fatal side effects including rhabdomyolysis, a rare condition characterized by the disintegration of muscle tissue and subsequent release of myoglobin into the bloodstream. 52 Myoglobin has been shown to damage kidney tissue and in some cases, lead to acute kidney failure.53

A 2003 German study concluded that individuals taking Baycol were 16-80 times as likely to develop Rhabdomyolysis compared to people taking other statins.54 In October 1999, the FDA openly recognized the dangers associated with the Baycol in a letter to the drugs maker which
50

Edwards, Jim. "Pfizer Exec: Company Approved of Off-Label Bextra Promotion | BNET ." BNET - The CBS Interactive Business Network. http://www.bnet.com/blog/drug-business/pfizer-exec-company-approved-of-off-label-bextrapromotion/1934 (accessed October 21, 2011).
51 52 53 54

Ibid

"Documents suggest Bayer knew Baycol problems - Page 2 - CNN." CNN.com. http://articles.cnn.com/2003-0223/justice/bayer.documents_1_baycol-bayer-philip-beck/2?_s=PM:LAW (accessed October 21, 2011) "Rhabdomyolysis - PubMed Health." National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001505/ (accessed October 24, 2011). M, Zeitlinger . "Clinico-pharmacologic explanation models of cerivastatin associated rhabdomyolysis." Wien Med Wochenschr. 153(11-12):250-4. (2003). http://www.ncbi.nlm.nih.gov/pubmed/12879633 (accessed October 18, 2011).

specifically stated that the medications package insert was minimized the risk of rhabdomyolysis.55 Even still, the FDA approved 0.8 mg dose of the drug in 2000 doubling the previously allowable amount. 56

The drug was recalled in August 2001 after it was linked to 53 deaths worldwide. More recently. researchers have discovered that the number of deaths attributable to Baycol exceeds 100. 57 There have been roughly 8000 personal injury lawsuits related to the drug which have obligated Bayer to pay victims more than $1.1 billion.58 Over 1000 more lawsuits are still pending.59

In 2004, officials with the Journal of the American Medical Association issued a public statement stating that the FDA is incapable of policing itself in matters of drug safety. The editors referenced Baycol in particular as a clear example of the agencys unresponsiveness and slowness in pulling dangerous drugs off the market. The JAMA authors also recommended that an independent oversight committee be commissioned to review the safety of approved pharmaceuticals. 60

Accutane (isotretinoin):

55

"Baycol (cerivastatin sodium tablets)." U S Food and Drug Administration Home Page. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm172265.htm (accessed October 12, 2011).
56

"Baycol Timeline -- Key Events in the History of the Recalled Cholesterol Drug Baycol | Market Wire | Find Articles." Business Library. http://findarticles.com/p/articles/mi_pwwi/is_20050229/ai_mark02051931/?tag=content;col1 (accessed October 18, 2011).
57

Homola, Victor . " BAYER SAYS IT FACES 400 MORE BAYCOL LAWSUITS - New York Times." The New York Times . http://www.nytimes.com/2003/02/06/business/company-news-bayer-says-it-faces-400-more-baycol-lawsuits.html? src=pm (accessed October 5, 2011).
58 59 60

"Baycol Lawsuits." Lawyers.com. http://toxic-torts.lawyers.com/Toxic-Torts/Baycol-Lawsuits.html (accessed October 4, 2011).

Ibid

Russel, Sabin. "FDA lax in drug safety, journal warns / Independent agency is sought to prevent conflicts of interest." SFGate. http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/11/23/MNGSPA04NI1.DTL (accessed October 24, 2011).

Manufactured by the the Swiss pharmaceutical company Hoffman-LaRoche , Accutane was approved by the FDA in 1982 as a treatment for severe cystic acne. Included in the long list of side effects that have been associated with Accutane are depression, psychosis, suicidal behavior, hepatitis, birth defects, acute pancreatitis, night blindness and inflammatory bowel disease.61 The FDA also advised users that it may stop long bone growth in teenagers who are still growing. 62

In a testimony before congress, Dr. Janet Woodcock, the director of the FDAs Center for Drug Evaluation and Research, spoke about the serious dangers posed by Accutane to its users noting that over a 20 year period, government authorities have received over 23,000 reports of adverse events in connection with the drug. Among the top five most commonly reported adverse events were induced abortion as well as suicidal ideation. 63 Woodcock's testimony before lawmakers came in 2002- about 7 years before the drug would finally be pulled from the shelves in June 2009. The drug's withdrawal was prompted not by the FDA, but Roche, which made the decision while facing a growing number of Accutane-related lawsuits. The drug is still being marketed by other firms internationally under different names.64

One prominent figure who opposed the drug was US Congressman Bart Stupak. Stupaks 17 year old son committed suicide with a firearm after taking the drug. Upon reviewing internal FDA

61

Edwards, Jim. "Acne Drug Accutanes Side Effect Is Death. So Why Is It Still on the Market? | BNET ." BNET - The CBS Interactive Business Network. http://www.bnet.com/blog/drug-business/acne-drug-accutanes-side-effect-isdeath-so-why-is-it-still-on-the-market/4240 (accessed October 10, 2011).
62 63 64

"Medication Guide- Accutane." FDA.gov. www.fda.gov/downloads/drugs/drugsafety/ucm085812.pdf (accessed October 12, 2011). "Concerns Regarding Accutane (isotretinoin)." FDA.gov. http://www.fda.gov/newsevents/testimony/ucm115126.htm (accessed October 18, 2011). Edwards, Jim. "Acne Drug Accutanes Side Effect Is Death. So Why Is It Still on the Market? | BNET ." BNET - The CBS Interactive Business Network. http://www.bnet.com/blog/drug-business/acne-drug-accutanes-side-effect-isdeath-so-why-is-it-still-on-the-market/4240 (accessed October 10, 2011).

documents, Stupak surmised that the FDAs estimate that 167 suicides had been caused by Accutane was inaccurate and that the number could be as high as 20,000. 65

James T. O Donnells book Drug Injury: Liability, Analysis and Prevention highlighted the debate over Accutane within the offices of the FDA. In 1990, the FDA's Dr. David Graham noted in one correspondence with his peers that the magnitude of injury and death has been great and permanent, with 11,000 to 13,000 Accutane-related abortions and 900 to 1,100 Accutane-related birth defects. There is no alternative to immediate withdrawal. 66 ODonnell also writes that 90% of the women who had been treated with the drug from 1982-1987 did not have severe cystic acne.67

So far, more than 5,000 personal injury lawsuits have been brought against Roche, the majority of which are still pending. 68 One case that has been settled involved New Jersey resident Andrew McCarrell, who developed inflammatory bowel disorder and had to have his colon removed after taking the medication. In 2010, he won a $25 million lawsuit against Roche. He won on the grounds that the labeling of Accutane did not adequately represent the risks involved. 69

65

Mitchell, Steve. "Hill committee: Accutane causes suicide - UPI.com." UPI.com. http://www.upi.com/Science_News/2002/12/11/Hill-committee-Accutane-causes-suicide/UPI-56881039653795/ (accessed October 2, 2011).
66 67 68

Donnell, James T.. Drug injury: liability, analysis and prevention. 2. ed. Tucson: Lawyers & Judges Publishing Company, 2005. Ibid Edwards, Jim. "Bad Data: How Quants Convinced Roche to Compromise Patient Safety | BNET ." BNET . http://www.bnet.com/blog/drug-business/bad-data-how-quants-convinced-roche-to-compromise-patient-safety/5354? tag=mantle_skin;content (accessed October 17, 2011).
69

"Accutane Lawsuit: Andrew McCarrell Wins $25 Million After Having Colon Removed." The Huffington Post. www.huffingtonpost.com/2010/02/17/accutane-lawsuit-andrew-m_n_465598.html (accessed October 13, 2011).

Cylert (pemoline):

In 2005, Abbot Laboratories discontinued its production of Cylert; a drug used to treat attention deficit hyperactivity disorder. After 30 years on the market, Cylert was removed by the FDA after public outcry over the medication's effects on liver health. During its time on the market, several studies concluded that the users of Cylert were much more likely to experience acute liver failure than the general population.

Cylert was responsible for at least 13 deaths and hundreds of serious adverse reactions.70 Cylert is a perfect example of how a harmful drug can remain in good standing with the FDA for many years even when it is known to be deadly and there are safer alternatives. After a 1995 study concluded that individuals taking Cylert were 45 times more likely to suffer liver failure, health authorities in the UK acted swiftly to pull the drug off the market. It would be another 10 years before the FDA agreed to do the same. 71

Even though the FDA required stronger warning labels that advised physicians to test the health of the liver of patients taking Cylert, agency documents reveal that these warnings went unheeded.72 This is a frightening notion considering that the agency wrote in one alert to health care professionals that the reporting rate for liver failure with pemoline is 10 to 25 times greater than the background rate of liver failure in the general population. 73
70 71

"Public Citizen Letter to FDA." citizen.org. www.citizen.org/documents/1389.pdf (accessed October 11, 2011).

DuBois, Shelley. "Why the EU banned Avandia but the FDA didn't - Sep. 24, 2010." CNNMoney . http://money.cnn.com/2010/09/24/news/companies/FDA_Avandia_GSK_ban.fortune/index.htm (accessed October 12, 2011).
72

Harris, Gardiner. "Citizens' Group Wants Hyperactivity Drug Taken Off the Market." The New York Times . http://www.nytimes.com/2005/03/25/business/25warning.html?pagewanted=print&position= (accessed October 24, 2011).
73

Moore, Elaine A.. The amphetamine debate: the use of Adderall, Ritalin, and related drugs for behavior modification, neuroenhancement, and anti-aging purposes. Jefferson: McFarland & Co., 2011.

In an open letter to the FDA's Acting Commissioner, Lester Crawford, the advocacy group Public Citizen raised concern over the use of pemoline and pointed out the critical fact that only about 10% of all adverse events are reported to FDA officials. Using the agency's own data on acute liver failure caused by pemoline, Public Citizen extrapolated that the actual incidence of liver failure among users of pemoline could be 168 times greater than in the general population. Further, the watchdog group claimed that the 13 deaths officially linked to Cylert is a deceptive underestimate of the actual figure.74

DES (Diethylstilbestrol)

DES was a synthesized form of estrogen widely used in the USA from 1940-1971 to prevent miscarriages and premature labor. A 1953 study carried out by the University of Chicago revealed that the drug was no more effective at preventing miscarriages than the placebo.75 Between 5 to 10 million women were prescribed DES by their physicians - even after its ineffectiveness had been established.76 In 1971, a study connected DES with an uncommon vaginal cancer known as clear cell adenocarcinoma in the daughters of women who had been given DES. In 1971, the FDA rescinded its approval of the drug to be used on pregnant women.77

The numerous health hazards linked to DES have become evident over the years. Research has shown that DES daughters are 30% more likely to develop breast cancer than the general

74 75 76 77

Public Citizen Letter to FDA." citizen.org. www.citizen.org/documents/1389.pdf (accessed October 11, 2011).

"DES timeline ." Boston.com. http://articles.boston.com/2011-04-18/lifestyle/29444354_1_des-education-desexposure-des-lawsuits (accessed October 24, 2011). "Ibid

Ibid

population.78 In addition, research has shown that DES daughters have higher rates of infertility and they are more likely to develop abnormal precancerous cells in the cervix.79 Among DES sons, the health risks posed by the drug are also significant. DES has been linked to non-cancerous epididymal cysts, genital abnormalities and infertility in DES sons. 80 These health complications have been found to extend to the grandchildren of DES users.81

On behalf of their constituents who were affected by the DES scandal, Massachusetts senators John Kerry and Scott Brown wrote a letter to FDA commissioner Margaret Hamburg in the winter of 2010 requesting that the agency issue an apology. In February 2011, the FDA responded in writing, calling the fallout from the misuse of DES a tragedy but did not apologize for their lack of oversight on this multi-generational health disaster.82

Determining how much money was paid out to victims of DES in court by the drugs various manufactures is a difficult task. Around 200 companies manufactured the drug. Many of the lawsuits brought against the manufacturers occurred decades after the damage had been done and most plaintiffs did not recall the company who produced the pills that they or their mothers had taken.83 Accordingly, in all cases settled after 1980, companies were required to compensate victims according to the percentage of the market share they held while the drug was being

78 79 80 81 82 83

Rothke, Joy. "Health Library Articles." HealthDay. http://consumer.healthday.com/encyclopedia/article.asp? AID=647261 (accessed October 12, 2011). Diethylstilbestrol (DES) and Cancer - National Cancer Institute." National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Risk/DES (accessed October 2, 2011).

Ibid
"Ibid

"John Kerry - United States Senator for Massachusetts: Press Room." kerry.senate.gov. http://kerry.senate.gov/press/release/?id=fd5e856f-6e84-4332-b434-3f17549071b5 (accessed October 7, 2011). Wehmhoefer, Richard A.. Statistics in litigation: practical applications for lawyers. Dubuque, Iowa: Shepard's/Mcgraw-Hill, 1985.

prescribed. A 1983 issue of Mother Jones reported that the Indianapolis-based pharmaceutical firm Eli Lilly was involved in DES-related claims that exceeded $3 billion in the 1970s. 84

Yaz (Drospirenone)

Bayers biggest moneymaking drug, Yaz is an oral contraceptive that was approved by the FDA in 2006. It is also used to treat premenstrual dysphoric disorder and moderate cases of acne. Known side effects of Yaz include blood clots, stroke and heart attack. While the drug has yet to be taken off the market, recent months have witnessed growing public concern over the safety of the popular medication.

Two 2011 studies on drospirenone determined that women taking the drug have a 2 to 3 times higher risk of deep vein thrombosis than women taking another contraceptive containing the synthetic hormone levonorgestrel.85 These findings were consistent with an FDA-run study that showed a 50% increase in the incidence of venous thromboembolism among women taking drospirenone.86 FDA authorities issued a statement in September 2011 saying that the agency has not yet reached a conclusion, but remains concerned, about the potential increased risk of blood clots with the use of drospirenone-containing birth pills.87

84 85

Johnson, JT, and Mark Dowie. "DES Revenge." Mother Jones, Feb. - Mar. 1983.

Gardner, Amanda. "FDA turns to advisory panel for Yaz safety analysis - USATODAY.com." USATODAY.com. http://yourlife.usatoday.com/health/medical/breastcancer/story/2011-09-27/FDA-turns-to-advisory-panel-for-Yazsafety-analysis/50568528/1 (accessed October 3, 2011).
86 87

Ibid

"FDA Drug Safety Communication: Safety review update on the possible increased risk of blood clots with birth control pills containing drospirenone." FDA.gov. http://www.fda.gov/Drugs/DrugSafety/ucm273021.htm (accessed October 25, 2011).

The FDA, in fact, quietly went about recalling several batches of Yaz in 2009 after Bayer failed to manufacture over 32,000 boxes of the product within specification.88 Jim Edwards of the bNet news network reported in 2010 that the recall went largely unnoticed because the agency chose to place the recall information in the small print of an Enforcement Report from November 25, 2009, on their website; not bothering to add it to the section titled Recalls, Market Withdrawals & Safety Alerts.89 Edwards also wonders how many women were exposed to tainted pills unnecessarily due to slow action by the FDA; he notes that the recall occurred over 6 months after the FDA inspected Bayers contraceptive drug.90

Overall, 285 cases of death has been reported to the FDA in connection to Yaz and over 3,000 cases of pulmonary embolism and 2,000 incidents of deep vein thrombosis both of which are potentially life-threatening.91 In the US and Canada, approximately 5,000 women have filed lawsuits against Bayer seeking compensation for injuries related to taking Yaz.92

Premarin

88

Edwards, Jim. "Did You Know the FDA Recalled Bayers Yaz Contraceptive? Neither Did Anyone Else | BNET ." BNET. http://www.bnet.com/blog/drug-business/did-you-know-the-fda-recalled-bayers-yaz-contraceptive-neither-didanyone-else/4754 (accessed October 2, 2011).
89 90

"Enforcement Report for November 25, 2009." FDA/gov. http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm192035.htm (accessed October 24, 2011). Edwards, Jim. "Did You Know the FDA Recalled Bayers Yaz Contraceptive? Neither Did Anyone Else | BNET ." BNET. http://www.bnet.com/blog/drug-business/did-you-know-the-fda-recalled-bayers-yaz-contraceptive-neither-didanyone-else/4754 (accessed October 2, 2011).
91 92

"Drug Report: Yasmin." Adverse Events. www.adverseevents.com/drugdetail.php? AEDrugID=2381&BrandName=YASMIN (accessed October 11, 2011). "VIDEO: Marketplace looks into alleged Yasmin risks - Health - CBC News." CBC.ca . http://www.cbc.ca/news/health/story/2011/01/20/yasmin-marketplace.html (accessed October 24, 2011).

This estrogen-based hormone replacement therapy is sold by Wyeth Pharmaceuticals (part of Pfizer since 2009) to alleviate the symptoms of menopause in women. First approved by the FDA in 1942, the drug is created from pregnant mares' urine hence its name.

Similar hormonal drugs marketed by Pfizer are Prempro and Premphase. The family of drugs has been linked to increased risk of cancers and promoting the onset of dementia in elderly women.93 Research carried out in the 1970s that appeared in the New England Journal of Medicine showed that Premarin increased the risk of developing endometrial cancer fivefold.94 A study undertaken in 1980 Boston university Medical Center concluded that roughly 15,000 cases of endometrial cancer could be attributed to the drug between 1971-1975 alone.95

Tens of thousands of cases of breast cancer and more than 1500 reports of death have been reported to authorities in connection with Premarin and its variations.96 Along with the litany of dangerous side effects attributed to the drug, many animal rights activists have raised objections over the production of Premarin which subjects mares to uncomfortable living conditions throughout their lives and results in the premature slaughter of horses.97 Despite all this, Premarin, Premphase and Prempro remain on the market.

93 94

Singer, Natasha, and Duff Wilson. "Menopause, as Brought to You by the Drug Companies." The New York Times . http://www.nytimes.com/2009/12/13/business/13drug.html?pagewanted=all (accessed October 24, 2011). Ziel, Harry K., and William Finkle. "Increased Risk of Endometrial Carcinoma among Users of Conjugated Estrogens." New England Journal of Medicine 293:1167-117 (1975). http://www.nejm.org/doi/full/10.1056/NEJM197512042932303 (accessed October 12, 2011).
95 96 97

Singer, Natasha, and Duff Wilson. "Menopause, as Brought to You by the Drug Companies." The New York Times . http://www.nytimes.com/2009/12/13/business/13drug.html?pagewanted=all (accessed October 24, 2011). "Search Results: Premarin." Adverse Events. http://www.adverseevents.com/searchresults.php?keywords=premarin (accessed October 9, 2011). "PMU Industry." Equine Advocates. http://www.equineadvocates.org/issueDetail.php?recordID=5 (accessed October 6, 2011).

Wyeth has successfully won most of the lawsuits brought against it connected with to damage from Premarin. Still, the company has paid hundreds of millions of dollars worth of compensation to victims and upwards of 10,000 cases are still pending.98 In a landmark case from 2008, Wyeth was ordered by a Nevada court to pay a combined $134 million to three women who developed breast cancer after taking Premarin.99 In 2009, a Philadelphia state court ruled in favor of two women in a lawsuit seeking compensation from Pfizer for damages related to the companys hormonal drugs. In total, the women were given a payout of $103 million.100 Bloomberg News reported in June 2011 that Pfizer agreed on a settlement of $330 million settling 2,200 separate claims from individuals seeking compensation for developing breast cancer related to the use of Prempro.101

98 99

"Potential Premarin Recall Lawsuit for its Side Effects." rotlaw.com. http://www.rotlaw.com/premarin/ (accessed October 5, 2011). . "Verdicts & Settlements January 14, 2008: Nevada woman wins $47.6M in hormone therapy case | Lawyers USA | Professional Journal archives from AllBusiness.com." AllBusiness.com. http://www.allbusiness.com/legal/tortsdamages/8890217-1.html (accessed October 9, 2011).
100 101

Wilson, Duff. "Another Loss for Pfizer in Hormone Drug Suits." The New York Times. http://www.nytimes.com/2009/11/24/business/24wyeth.html (accessed October 24, 2011). Feeley, Jef. "Pfizer Said to Pay $330 Million to Settle Prempro Lawsuits Claiming Cancer - Bloomberg." Bloomberg . http://www.bloomberg.com/news/2010-08-27/pfizer-settles-arkansas-prempro-case-before-retrial-over-punitivedamages.html (accessed October 2, 2011).

Looking Ahead at the FDA and Pharmaceutical Drugs

An impartial investigation of the FDAs record on prescription drugs reveals a sordid history defined by rampant negligence and depraved subservience to special interests. By allowing these drugs to be released and remain available to consumers despite ample evidence of their toxicity, the FDA has failed to protect the health and safety of Americans. The decisions of this group are directly responsible for the death of tens of thousands of people and the injury of hundreds of thousands more.

We are currently in the midst of a national health crisis marked by soaring rates of obesity, diabetes and cancer. As the health of Americans declines, more and more people are turning to a dizzying array of prescription medication for help. A 2010 report from the CDC showed that spending on prescription drugs in 2008 topped $234.1 billion more than double what Americans were paying in 1999.102 If the standards drug safety enforced by the FDA continued to be left unchecked, we can
102

" Data Briefs - Number 42 - September 2010." Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/databriefs/db42.htm (accessed October 19, 2011).

expect to see unprecedented death and injury from taking pharmaceuticals in the coming years. It is therefore more important than ever that we hold the FDA accountable for approving harmful drugs and failing to remove them once are on the market. We must demand that measures be implemented that ensure comprehensive oversight and transparency in the FDAs drug review process. Anything less than a complete overhaul of the current system will undoubtedly send us on a dangerous path of medical tyranny that we cant afford to tread.

Dr. Gary Null is the host of the nations longest running public radio program on nutrition and alternative medicine, and a multi-award-winning director of progressive documentary films, including Vaccine Nation (2008) and Autism: Made in the USA (2009) Jeremy Stillman is a Research Associate with the Progressive Radio Network. Endnotes