7 Drugs That Big Pharma Withdrew and Hopes You’ve Forgotten About
Do you remember the drugs Vioxx, Bextra, Baycol, Trovan, Meridia, Seldane, Hismanal, Darvon, Raxar and Redux? Pharma hopes not. How about Mylotarg, Lotronex, Propulsid, phenylpropanolamine (PPA), Prexige, phenacetin, Oraflex, Omniflox, Posicor, Serzone and Duract? After deaths and serious side effects surfaced, these meds went from wonder drugs to wonder-why-they-were-approved drugs and were withdrawn.
In some cases, there is little evidence the drugs were ever used or widely marketed or that anyone was injured. In certain cases, the withdrawn drugs were on the market for less than a year before things went “terribly wrong.” In other cases, the drugs were in wide use for decades despite well-recognized risks and pleas from public health figures to pull them. In almost all cases, Pharma companies maintained the drugs were safe and stuck to their story for as long as they could—not just to protect the company image and stock price but also to avoid adding fuel to injury lawsuits. ("The drug was so unsafe it was pulled” does not look great in court.)
When it comes to drug approvals, there is a basic tension between Pharma and regulators. The quicker a drug is approved, the more dangerous a drug potentially is but also the more quickly Pharma makes money. Since passage of the 1992 Prescription Drug User Fee Act (PDUFA), which lets Pharma pay the cash-strapped and underfunded FDA to “expedite” drug approvals, the scales have tipped toward Pharma and the time to get a new drug to market has decreased. While Pharma and the FDA have always been too collegial (and, with 23 industry links, the new FDA Commissioner Robert Califf essentially works for Pharma), PDUFA allowed drug companies to pay for approval and for safety to be “bought.” It should be noted that drugs expedited under PDUFA are not intended for serious and fatal conditions—separate FDA programs cover those.
PDUFA is not the only reason for quicker approvals. Clinical trials, which have to be approved by Institutional Review Boards (IRBs) to ensure ethical treatment of human subjects, used to occur in hospital and academic settings and take years. Now trials are conducted by for-profit groups called contract research organizations (CROs), which are owned and operated by Pharma. The trials themselves are increasingly conducted overseas. The IRBs themselves have also become for-profit. “The problem is that commercial IRBs are paid in full by the very companies conducting the research,” said a Public Library of Science (PLOS) article. “Anyone who can bring together five people, including a community representative, a physician, a lawyer and an ‘ethicist,’ can set up” an IRB.
Because of for-profit CROs and IRBs and the Prescription Drug User Fee Act, drugs are rushed to market with “post-marketing surveillance” replacing the lengthy human trials that used to be the norm—meaning a drug is literally presumed safe until it’s proved otherwise so Pharma can start making money. Why should patients have to wait for another “treatment option,” says Pharma, pretending to be selfless. Needless to say, the “market first/assess safety second” approach results in many deaths and injuries and Pharma simply builds injury settlements into its high costs. For example, Merck set aside $950 million to pay for Vioxx injuries—a mere fraction of the $3.4 billion a quarter it was earning.
Most people remember the withdrawal of Vioxx and the Bayer statin Baycol, but here are other drug withdrawals Pharma hopes you have forgotten about. This list of seven is far from complete... and it continues to grow.
Eli Lilly’s new pain reliever Oraflex (an NSAID, nonsteroidal anti-inflammatory drug) introduced in 1982 might have had the shortest life span of any approved drug: after only 10 weeks on the U.S. market, there was bad news from the U.K. where the drug was already in use. The British Committee on the Safety of Medicines told the FDA it knew of 3,500 adverse side effects from the drug including 61 deaths. The FDA then admitted it also had reports of 11 U.S. Oraflex deaths from associated kidney and liver damage and the drug was withdrawn.
Even in 1982, too-rapid drug approvals were becoming a safety factor. ''Oraflex shows that the FDA has already begun speeding up the review process,'' said Dr. Sidney Wolfe, former director of Public Citizen’s Health Research Group. ''It demonstrates that the process should be made more thorough instead of less so.'' Then, like now, Pharma defended its dangerous drugs and called the FDA overcautious. Lilly said the decision to withdraw Oraflex from the market “resulted from overwrought, unsubstantiated criticism of the drug,” wrote the New York Times. “The drug had not been on the market long enough to gain widespread, politically powerful support among doctors and arthritis patients,” whined Lilly.
Like Oraflex, Abbott’s antibiotic Omniflox was only on the market for a few weeks before serious adverse reports surfaced in 1992. More than 100 patients experienced adverse reactions like allergic events and hemolytic anemia during the first four months of use. There were also "several cases of severe low blood sugar, especially in very elderly patients with decreased kidney function," said the FDA. Half of the patients who incurred kidney dysfunction on Omniflox needed dialysis, said the FDA, and others suffered liver dysfunction.
Omniflox is part of a class of antibiotic drugs called fluoroquinolones, which continue to force Pharma withdrawals. The Pfizer antibiotic Trovan was linked to 14 acute liver failure cases and six deaths during its first year of use, 1997; the next year it was withdrawn. (During a 1996 Nigerian meningitis epidemic, Trovan was linked to the death of 11 children before it was approved for U.S. use.) During the same time period, ï¿¼Raxar, a fluoroquinolone antibiotic from Glaxo Wellcome, was also withdrawn from the market after links to heart rhythm problems and sudden death. Four patients had died during clinical trials, two likely from heart rhythm disturbances, but approval went ahead.
This spring, 24 years after Omniflox’s withdrawal, the FDA no longer recommends the drug class. The serious side effects “generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options,” it wrote.
Wyeth-Ayerst Laboratories’ Duract, marketed in 1997, was also an NSAID painkiller. While NSAIDs are considered so safe they are sold over the counter, there was evidence of liver risks with Duract. Patients in long-term studies had showed dangerously elevated liver enzymes and an FDA medical officer said that in his judgment, Duract caused more liver cell damage than any other similar medication available. "We have seen a 'liver flag,’” he warned.
Before any patient deaths were reported, the FDA told Wyeth-Ayerst to put a black box on Duract packages warning against using the drug beyond 10 days, but reports of liver injuries kept surfacing. In fact, it was estimated that one of every 20,000 patients who took Duract suffered serious injury. After four patients died and eight required liver transplants, the drug was taken off the market.
There was a safety cloud over this widely marketed diet drug immediately after its 1997 approval. According to FDA records, 30 people died of cardiovascular problems from 1997 to 2003, and 224 others experienced nonfatal strokes, heart attacks and other cardiovascular ailments.
Instead of pulling Meridia from the market, the FDA relied on warnings on Meridia’s label to protect patients as it does with so many dangerous drugs. Meridia was only recommended for people with 30 pounds or more to lose, said the FDA, with no poorly controlled hypertension and no history of heart disease, stroke or severe liver or kidney disease. How many overweight people are free from such conditions, which are so often linked to obesity?
FDA reviewer and highly respected safety advocate Dr. David Graham in congressional testimony in 2004 listed Meridia among drugs that were so dangerous their sales should be limited or stopped. The drug was not withdrawn until 2010.
Meridia was not the only diet drug linked to heart problems and deaths. Who remembers Fen-Phen—the combo of fenfluramine and phentermine? Even as millions of Americans were finally losing their saddlebags and muffin tops because the drug actions of Fen-Phen actually worked, “Fen,” marketed by a company that later became Wyeth and then became Pfizer, was linked to potentially fatal pulmonary hypertension and heart valve problems and withdrawn.
Like so many withdrawn drugs, the serious side effects could have been predicted. A similar drug to Fen had already been linked to lung damage, and the book Dispensing with the Truth: The Victims, the Drug Companies, and the Dramatic Story behind the Battle over Fen-Phen claims that one of Wyeth’s own reports listed cases of pulmonary hypertension connected to Fen-Phen including 101 deaths. The book also says a company memo condemned the idea of an FDA heart and lung warning on the drug’s label because it would cost the company $800 million in revenue.
6. Darvon and Darvocet
The public watchdog group Public Citizen first called on the FDA to ban or severely restrict the painkillers Darvon and Darvocet in 1978, but they were not banned until 2010. According to Public Citizen, the drugs are “toxic at doses not much higher than the recommend dose because a heart-toxic metabolite accumulates in the body” and the drugs have been “linked to many thousands of U.S. deaths since 1981, a large proportion of which were likely caused by cardiac toxicity, including the interruption of electrical conduction in the heart.”
While the U.K. banned the drugs in 2005, the FDA waited until 2010 to ban them, likely causing 1,000 to 2,000 or more deaths, said Public Citizen. In four years in Florida alone, 395 deaths were "caused" by the drug, Public Citizen charged.
Like Omniflox and Oraflex, GlaxoSmithKline’s Lotronex, a drug for Irritable Bowel Syndrome (IBS), was on the market for less than a year before reports of deaths and serious injuries surfaced. Within a few months of release, there were five deaths from inflammation and injury of the small intestine, 49 cases of inflammation and injury of the large intestine and 21 cases of severe constipation, 10 of which required surgery. Hospitalizations and more serious injuries followed. The drug was withdrawn.
Still, Lotronex was brought back with restricted conditions and an awareness campaign about IBS from actress Lynda Carter, who had played Wonder Woman in the 1970s TV series. "IBS has been so shrouded in darkness," said Carter. "I know the truth about how people suffer. It is just one more closeted condition that we need to shine some light on."
"While IBS is not a life-threatening disorder, it does impact the individual's quality of life,” agreed an article promoting Lotronex in USA Today.
That assurance could be said about most of Pharma’s withdrawn drugs: they treated non-life-threatening disorders... until life-threatening side effects developed.