Evelyn Pringle March 6, 2006
On January 3, 2006 the Global Exchange Report named the top fourteen “Worst Corporate Evildoers” in the world for 2005. Pfizer, one of the most profitable drug companies on earth, with sales over $52 billion in 2004, made the list of Evildoers.
Pfizer’s participation in the cover-up of the deadly side effects of Bextra surely contributed to its membership. Because the drug was promoted and sold off-label for so many unapproved uses, the company made hundreds of millions of dollars in pure profits during Bextra’s short life on the market. However, experts predict that when all is said and done, the total amount of the drug’s damage to consumers will be in the billions.
Bextra belongs to the same class of drugs as Vioxx and Celebrex, known as Cox-2 inhibitors. Millions of people world-wide have taken these drugs.
It is now apparent that Pfizer knew Bextra was associated with extremely harmful side effects long before it was yanked off the market. However, Pfizer had good reason to stall its inevitable removal after Vioxx was recalled.
Bextra was on the market for about 3.5 years, but did not reach its full sales potential until Vioxx was eliminated from the competition. After the Vioxx recall, in one month alone, Bextra prescriptions went from 1.15 million in September 2004, to 1.48 million in October. All total for 2004, Pfizer generated sales of about $1.3 billion.
The marketing history of Bextra involves a train of suspicious conduct. On November 16, 2001, the drug’s original maker, Pharmacia won FDA approval for treatment of pain associated with osteoarthritis, adult rheumatoid arthritis and menstrual pain only and immediately went into overdrive promoting the drug for off-label use.
In July 2002, Pfizer acquired Bextra from Pharmacia in a $58 billion dollar deal that was not approved by the FTC until the following year in April 2003.
An FDA Talk Paper on the agency’s web site on November 15, 2002, announced new warnings on Bextra and said, “labeling is being updated with new warnings following postmarketing reports of serious adverse effects including life-threatening risks related to skin reactions – including Stevens Johnson Syndrome, and anaphylactoid reactions.”
The following month, the “Congress of California Seniors,” filed a lawsuit against Pharmacia in a Superior Court in Los Angeles, alleging the company had illegally promoted Bextra for off-label use.
According to the group, after the FDA refused a request to approve Bextra for pain related to impacted molars, Pharmacia helped fund a study that claimed Bextra could be useful in fighting acute dental pain and got it published in dental journals which led to the suit alleging secretive encouragement of ‘off label’ uses and attempting to circumvent the FDA’s refusal.
On November 2, 2003, after a year-long analysis of prescribing records, Knight-Ridder reported that more than half of Bextra pills sold were for off-label use.
About 5 months later, on March 14, 2004, Pfizer disclosed in a regulatory filing that the Justice Department was investigating the company’s marketing practices of Bextra for uses not approved by the FDA.
In October, 2004, the New England Journal of Medicine carried two editorials calling for renewed scrutiny of all Cox-2 inhibitors to assess whether the other drugs also caused heart problems.
In one editorial, cardiologist, Eric Topol, one of the first people to raise a red flag on Vioxx, from the Cleveland Clinic in Ohio, called for a government investigation into why Merck and the FDA allowed Vioxx to remain on the market for so long after its association with heart risks were revealed.
The FDA’s inaction was also noted by the Washington Post pointing out that in the late 1990s, the FDA took action when safety concerns were raised by withdrawing 10 drugs within 3 years. “But until the Vioxx withdrawal, only one other drug had been pulled since the Bush administration began, leading some to conclude that the agency had made a quiet policy change that emphasized “benefit” and sought to manage “risk” less intrusively,” the Post said on April 11, 2005.
As it turns out, Pfizer knew Bextra was every bit as dangerous as Vioxx and that the incidence of heart attack and stroke among patients using Bextra was more than 2 times that of patients taking placebos, which was revealed in a study presented on November 9, 2004, during the annual meeting of the American Heart Association in New Orleans.
Dr Curt Furberg, a professor at Wake Forest University School of Medicine, helped conduct the study and said: “Basically, we showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information.”
On November 18, 2004, Dr David Graham, head of the FDA’s Office of Drug Safety, testified before the Senate Finance committee and listed Bextra as one of five drugs whose safety needs ”to be seriously looked at.”
On December 9, 2004, the FDA announced that Bextra would come with a new bolded warning contraindicating its use in patients undergoing coronary artery bypass graft (CABG) surgery.
The FDA knew Bextra was being widely marked for off-label use. Its December 9, Talk Paper, noted that Bextra was “not approved for use in the treatment of postoperative pain of any type;” but added: “however, FDA believes that these new findings should be made available to healthcare professionals and patients, and the bolded warning specifically contraindicates Bextra for treatment of pain immediately following CABG.”
The FDA also ordered a black boxed warning on the label stating that patients taking Bextra had reported serious, potentially fatal skin reactions, including Steven-Johnson Syndrome and toxic epidermal necrolysis.
Come to find out, as of November 2004, the FDA had received reports of 87 cases of SJS associated with Bextra. Thirty-six patients required hospitalizations, and 4 people died. Twenty involved patients with a known allergy to sulfa.
Although the other Cox-2 selective inhibitors also showed a risk for SJS, the FDA found reported cases to be greater with Bextra.
SJS is a devastating reaction affecting the skin and mucous membranes, causing severe burning, blistering and sloughing of involved tissue. SJS commonly causes blindness and results in death in 10 to 30 percent of the cases, according to a December 12, 2004 press release by the SJS Foundation.
People also develop SJS as a reaction to other commonly prescribed drugs, including antibiotics, anti-convulsants, and non-steroidal inflammatory drugs (NSAIDS), including over-the-counter drugs such ibuprofen products.
On January 26, 2005, Jean Farrell McCawley, the founder of the SJS Foundation testified before a joint meeting of the FDA’s Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee.
Ms Farell-McCawley told the panel that although SJS was referred to as a rare skin reaction, since 1995, the SJS Foundation had been notified of far more cases of the condition than those recorded by the FDA.
By one estimate, each year, SJS effects three to eight people per million in the US. However, the frequency is thought to be much higher since the FDA acknowledges that only between one and 10% of all adverse drug reactions are reported each year.
“SJS is not as rare as we are led to believe,” Ms Farrell McCawley advises. “During the winter months, we learn of 15 new cases a week, and that’s only people with Internet access,” she says.
It is hard to imagine a more severe adverse drug reaction than SJS. In the April 2005 SJS Newsletter, SrA Tanner Claybaugh published a letter describing what his sister, Mollie, went through after developing SJS as a reaction to children’s Advil.
Shortly after taking drug, Mollie developed blisters and rashes all over her body and was hospitalized. “She was put in the Intensive Care Unit (ICU) where there were countless machines keeping her alive,” SrA says.
“After about a weeks time,” he continued, “she was put in the burn unit as if she had burns from a fire, but the allergic reaction was the cause of her third degree burns.”
She was hanging on to life by a thread for weeks. “Back and forth she went,” her brother said, “from the burn unit to ICU.”
“As soon as her condition improved it worsened,” he noted. “It was always the same pattern entering ICU,” he recalls, wash your hands with warm water and soap and then put on medical mask and gloves.
“I was an 11 year old boy,” he wrote, “who had to do this just to watch my sister through a glass door of an isolation room.”
Mollie’s head had to be shaved and her skin was covered in blisters. “Her whole body was wrapped in gauze to stop the bleeding blisters,” SrA recalls.
“I remember sitting in her burn unit room watching two therapists lift her up and try to sit her in a wheelchair,” he said and described how drops of blood would fall from Mollie’s burnt flesh.
SrA says Mollie could not even scream out in pain. “All she could do is cry because her vocal cords had been burned,” he said.
After five months in the hospital Mollie was allowed to go home.
“Our living area transformed into that of a hospital room,” SrA said, “it had a ventilator for her tracheotomy, IV stand, stomach tube stand, heart rate monitor, and medications galore.”
Therapists came everyday and a nurse was always with Mollie giving her care. She required surgeries almost every other week to stretch her esophagus and the ligaments in her feet and hands. She also had cornea surgery.
According to SrA, today Mollie cannot walk, see, or talk very well. “She is fed through a stomach tube and it’s hard for her to breath,” he says.
Before SJS, Mollie was a dancer. “She was suppose to perform in the opening show for the 1996 Olympics in Atlanta,” her brother says. However, the room where she used to practice her dance moves and back flips has now become a rehabilitation center.
SrA says Mollie cannot receive any more therapy because of the healthcare budget cuts so his mother became a nurse to take care of Mollie.
SrA believes there needs to be more public awareness of the dangers associated with the drugs that cause this horrible reaction.
In January 2005, the Bextra related cardiovascular problems were back in the news when the results of two trials were released that showed the drug tripled the incidence of heart attack and stroke in coronary bypass graft surgery patients.
On February 14, 2005, the Associated Press reported that while Vioxx and Celebrex increased patients’ risk of heart attack and stroke by about 20 percent, Bextra increased the risk by 50%, citing a study by WellPoint Inc.
In April 2005, Pfizer finally took Bextra off the market at the request of the FDA. At the same time, the FDA told Pfizer to include a black box warning on Celebrex.
In a prepared statement, Pfizer reported that the FDA said Bextra’s risk to the heart was not distinguishable from other drugs and that it was the skin reaction that led to the decision.
The FDA advisory said it “concluded that the overall risk versus benefit profile is unfavorable and has requested that Pfizer, the manufacturer of Bextra, voluntarily withdraw Bextra from the market.”
The FDA explained that the request to recall the drug was based on:
1) The lack of adequate data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse CV events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use.
2) Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The risk of these reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa allergy, and after both short- and long-term use.
The FDA also cited a lack of any demonstrated advantages for Bextra compared with other NSAIDs and instructed patients taking Bextra to contact their physicians and consider alternative treatments.
At the same time, FDA officials said all painkillers in the category known as “nonsteroidal anti-inflammatory drugs,” or NSAIDS, would have to carry stronger warnings about risks of heart attack, stroke, ulcers, internal bleeding or skin reactions, the Philadelphia Inquirer announced on April 9, 2005.
The warnings affected dozens of medications sold by prescription, as well as over-the-counter, with worldwide sales of at least $18.7 billion, according to the British pharmaceutical research firm Lead Discovery.
The drugs included Wyeth’s biggest-selling over-the-counter product Advil, which had sales of $620 million in 2004, Wyeth spokesman Doug Petkus told the Inquirer.
Teva Pharmaceutical’s ibuprofen, diclofenac and naproxen were included as also McNeil’s biggest-selling NSAID Motrin.
A report in the San Francisco Chronicle on February 27, 2005, said the “painkillers Vioxx, Celebrex and Bextra may go down in history as a classic example of the danger posed by aggressive industry promotion of prescription drugs to both patients and doctors.”
“In 2003,” the report said, “their manufacturers spent more than $1.5 billion to promote the drugs through television spots, print ads and pitches to doctors,” the report wrote.
And the $1.5 billion turned out to be a sound investment because by 2003, combined sales of the 3 drugs topped $5.3 billion, according to IMS Health, a pharmaceutical information and consulting company.
People who helped derail this deadly money train by standing up to the giant drug makers responsible for marketing this class of drugs often end up with a bitter pill. In the third civil lawsuit against Vioxx, Dr Topel gave testimony against Merck in a deposition and less than a week after his videotaped testimony was played in a Houston courtroom, he lost his title as chief academic officer of the Cleveland Clinic’s medical college.
On December 10, 2005, Dr Topol told the New York Times he was fired as a result of going up against Merck and said in part:
“The hardest thing in the world is just trying to tell the truth, to do the right thing for patients, and you get vilified. No wonder nobody stands up to the industry.”
But the icing on the cake for the Cox-2 inhibiter saga came on December 2, 2005, when Gooz News ran an article titled, “Pricey Pain Pills No Better at Reducing Tummy Distress.”
“It looks like the billions spent on expensive new Cox-2 inhibitors,” Gooz said, “was wasted – and not just because Vioxx was the likely cause of tens of thousands of heart attacks among its users.”
Citing a report in the British Medical Journal that day, Gooz said that “Cox-2 inhibitors do not reduce the gastrointestinal side effects of over-the-counter pain pills like ibuprofen.”
“This was the whole rationale for justifying the drug industry’s massive investment in this new class of medicines,” Gooz noted, “since they don’t reduce pain any more effectively than older pain pills.”