Are We Big Pharma's Guinea Pigs? 8 Drugs Used by Millions Before Being Pulled for Dangerous Side-Effects
Blockbuster drugs like Viagra, Lipitor, Prozac and Nexium have made Big Pharma one of the nation's top industries. Even before direct-to-consumer advertising on TV, there were blockbuster drugs like Ritalin, Valium, Tagamet and Premarin. To be a blockbuster a drug has to 1) be usable by almost everyone; 2) be used every day; 3) be used indefinitely; 4) solve an everyday health problem like heartburn or high cholesterol; 5) have a fun or memorable ad campaign; 6) get social buzz; and 7) be sold to a large number of people quickly.
The last qualification—quick sales to millions—is crucial because Big Pharma has a small sales window before a patent runs out. But it's also dangerous because many risks don't emerge until millions take the drug so the public serves as unwitting guinea pigs. In fact, the "early user/guinea pig" factor is what sunk Vioxx 10 years ago.
Because of patent pressure, minor drug risks are often only admitted when the patent runs out, a ruse AlterNet has written about. But when risks can't be ignored, even if the drug is selling briskly, the drug will be unceremoniously withdrawn and seldom mentioned again. Here are some blockbusters in the drug graveyard that Big Pharma hopes we will forget about.
1. Darvon and Darvocet
Is an opioid-linked medication that relieves pain worth the overdoses, death, addiction and abuse that are often in its wake? It is a question we hear today with drugs like OxyContin, but dates all the way back to 1957 when Eli Lilly began marketing Darvon.
Darvon and Darvocet (Darvon with acetaminophen, approved in 1972) were synthetic weak opioids that found themselves under safety clouds almost from the beginning. In 1978, Public Citizen called for their ban or severe restriction due to heart toxicity and deaths. Instead of banning or restricting Darvon, the government allowed Lilly to run an “educational program” about the risks. How did it work out? Lilly "converted its education program into a marketing initiative," said the Department of Health Education and Welfare. No kidding! In 2004, Darvon was still the 12th highest selling generic in the U.S. with 23 million prescriptions filled.
In 2006, Public Citizen again called for a ban saying that Darvon had been linked to 10,000 confirmed U.S. deaths since its introduction and that coroners "note its presence in more deaths each year than most other prescription drugs." Why is Darvon so lethal? A dose and overdose are very close in strength, it is extremely toxic when mixed with alcohol, it eliminates slowly from the body and it appears to be impervious to naloxone, the drug carried by beat cops and paramedics to treat/reverse heroin overdoses.
Finally, in 2010 the FDA heeded the decades of warnings and banned Darvon and all products containing Darvon. The ban came five years after the United Kingdom began withdrawal of the drug.
Pills that promise weight loss are never hard to sell and Abbott's Meridia offered the added benefit of a "high," since it was closely related to amphetamines. Debuted in 1997, as direct-to-consumer advertising was beginning, Meridia ads showed overweight women crediting the drug with giving them more will power while the ads simultaneously warned of heart and other health risks and "dependence" in those who abused the controlled drug.
When it came to safety, there was a cloud over Meridia even before it was approved. In 1996, an FDA advisory committee voted 5 to 4 that the drug's benefits did not outweigh its risks. In 2002 Public Citizen petitioned the FDA to ban the drug for its heart and cardiovascular risks revealed in several studies. In 2009 there were 84 reports of Meridia deaths from cardiovascular reasons in the FDA Adverse Event Reactions database.
Still, three years after its approval, Meridia had been used by 2 million people in the U.S. and was widely marketed in other parts of the world as Reductil, Siredia and Sibutrex. It was not until 2010, after Meridia was sold for 13 years, that Abbott withdrew it from the U.S. market under FDA pressure.
Some of Meridia's quick rise stemmed from it being approved just as Fen-Phen was withdrawn. Pondimin or "fen" (fenfluramine) was not popular until marketers combined it with phentermine. Fen-Phen certainly took pounds off but in combination, fen was linked to at least 41 cases of pulmonary hypertension, a rare lung disorder in which arteries narrow and can cause high blood pressure, valve problems and possible right heart failure. American Home Products (which became Wyeth, then Pfizer) quickly developed Redux, a similar drug to fen that it hoped would be safer. But in 1997 the FDA withdrew both drugs for heart valve problems.
Perhaps no blockbuster drug equaled the crash and burn of Merck's Vioxx. Billed as "super-aspirin" for everyday pain whether menstrual or arthritis, Vioxx was aggressively advertised by celebrity athletes like skater Dorothy Hamill and track star Bruce Jenner as a wonder drug. Except that it wasn't.
The Vioxx saga was the first time in recent memory that the possibility of deliberate Pharma subterfuge surfaced. Even as 20 million people were using Vioxx, it was found to double the risk of heart attack—and Merck was reported to have known about the risk. According to many news reports, Vioxx's cardiovascular risk data was deliberately withheld from the FDA, medical journals, the drug-taking public and their doctors, presumably so Merck could get its "patent's worth."
In Merck's 1999 annual report announcing Vioxx, the drug giant could barely contain its glee. "Vioxx—Our Biggest, Fastest and Best Launch Ever!" it trumpeted, predicting the drug would graduate from being a mere painkiller to preventing Alzheimer's disease and colon cancer. Instead, Merck found itself compensating 20,591 heart attack and 12,447 stroke plaintiffs in 2010 out of a $4.85 billion settlement fund. Some press reports placed the number of heart attacks linked to the super-aspirin at 140,000.
Increasingly, Big Pharma is eyeing poor countries to market, manufacture and test new drugs and the story of Trovan is a case in point. During a meningitis epidemic in Nigeria in 1996, Pfizer administered the not-yet-approved antibiotic Trovan to children, 11 of whom died while others sustained permanent injuries. Nigerian officials said Pfizer "unlawfully conducted a clinical trial without obtaining a valid clinical trial certificate," and failed to obtain required approvals and consent from the patients.
Pfizer "strongly disagree[d] with any suggestion that the company conducted its study in an inappropriate and unethical manner," contending it was trying to help with a meningitis outbreak that killed more than 12,000 children in six months near Kano. Pfizer paid the Nigerian government and state of Kano millions in a settlement, but Wikileaks documents suggested that Pfizer tried to extort Nigeria's former attorney general to drop the lawsuits.
In 1998, two years after the deaths and safety questions, the FDA inexplicably approved Trovan for use in the United States, though not in children. During its first year, 300,000 patients a month were prescribed Trovan and it made $160 million. Investors predicted it would be a $1 billion-a-year drug. But during its first year, the FDA cautioned doctors of 14 acute liver failure cases and six deaths linked to Trovan. Less than two years after its approval, U.S. regulators forced Pfizer to withdraw Trovan because of its liver toxicity.
If doing the same thing and expecting different results describes insanity, the FDA is clearly insane. A year before it approved Trovan, it approved the antibiotic Raxar which was linked to heart rhythm problems and sudden death. Raxar was withdrawn from the market in 1999 and there were even questions about its original safety testing.
Direct-to-consumer advertising, which began in the late 1990s, is widely credited with popularizing "GERD" (gastroesophageal reflux disease), a condition that was largely known as heartburn before TV drug ads. Soon an array of preparations like Nexium, Prevacid and Prilosec debuted which became blockbusters despite their links to osteoporosis and the dread diarrhea condition C. difficile.
One GERD medicine that lost out on the gravy train was Propulsid. Approved in 1993, by 1999 there were 341 reports of heart rhythm abnormalities and 80 reports of deaths. In 1998, Propulsid sales exceeded $1 billion even as warnings were added to the dangerous drug. Amazingly, Johnson & Johnson promoted Propulsid for children as well as adults and 20 percent of babies in neonatal intensive care units received it, according to a survey. After all, don't babies "spit up"? In 2000, Janssen Pharmaceutica, part of Johnson & Johnson, announced it would stop marketing Propulsid.
6. and 7. Seldane and Hismanal
Direct-to-consumer advertising also boosted seasonal allergies. But even as Claritin, one of the first advertised drugs, became a household word, the older antihistamines Seldane and Hismanal were under safety clouds. Seldane, an early non-drowsy antihistamine approved in 1985, was linked to heart problems especially when taken with certain antibiotics or antifungal drugs. Hismanal, approved in 1988, was linked to cardiovascular events and deaths and dangerous when combined with some antibiotics, AIDS drugs and antidepressants, said the FDA. Both drugs were withdrawn after millions used them and profits were taken. In Seldane's last year, 4.3 million prescriptions were written for the dangerous drug. Hismanal made $180 million a year in its last years.
Baycol was an early statin that tried to compete with Lipitor. Guess who won? Approved in 1997, Baycol was withdrawn in 2001 after postmarketing surveillance revealed 52 deaths from rhabdomyolysis and 385 nonfatal cases. Rhabdomyolysis is a condition seen with statins in which muscle tissue breaks down and can lead to kidney failure. Made by the drug giant Bayer, Baycol did well for itself, making between $900 million to $1 billion a year before its withdrawal. So sorry.
While Baycol's rival, Lipitor, went on to be the best-selling drug in the world, questions remain about the popular statin drugs. In 2012, the FDA made a label change to all statins warning of diabetes, liver injury, muscle damage and memory impairment. The warnings came the year Lipitor went off patent.