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OXYCONTIN UNDER FIRE
Pain pill leaves death trail
A nine-month investigation raises many questions about Purdue Pharma's powerful drug OxyContin.
By Doris Bloodsworth
Sentinel Staff Writer
October 19, 2003
Sylvia Cover remembers her husband telling the physician, "Just fix me up, Doc, so I can get back to work and take care of my family."
Six months later, Gerry Cover was dead.
Hooked on a powerful painkiller called OxyContin, the 39-year-old handyman and father of three died from an accidental overdose. The drug had been prescribed by his doctor for a mild herniated disc.
The Kissimmee man's death in September 2000 was an individual family's tragedy. But a nine-month investigation by the Orlando Sentinel found a broader, more disturbing pattern: During 2001 and 2002, more than 200 deaths statewide have been linked to the highly potent painkiller that has been criticized as being aggressively marketed and eagerly prescribed with only routine oversight from government regulators.
OxyContin, made by Purdue Pharma of Stamford, Conn., is a 12-hour time-release drug with the same potential for abuse and addiction as morphine.
The active ingredient in OxyContin and dozens of other strong painkillers is oxycodone, which comes from the opium poppy. The drug is so powerful it is sometimes called "heroin in a pill." It most recently has been linked to a prescription-drug investigation involving conservative commentator Rush Limbaugh.
The Sentinel's investigation tracked how three key forces -- Purdue's strong marketing campaign, the government's lax controls and a medical community unschooled in OxyContin's true power -- have contributed to a wave of addiction and death.
In turn, illegal use of the medicine has grown as more patients have become dependent on the drug and a new black market has emerged.
Jim McDonough, head of the governor's Office of Drug Policy, said he found the results troubling in light of unreleased reports that show oxycodone overdoses in Florida for the first half of this year continue to rise. He plans to respond with a number of legislative and educational proposals to counter what he called "overwhelming salesmanship to expound on the benefits of these drugs without enough cautions."
"There always was that suspicion when you did have data surrounding the death scene that the predominant drug that seemed to be there was OxyContin," McDonough said.
"If this was a rash of crimes resulting in death . . . we wouldn't stand for it."
The U.S. Food and Drug Administration, which approved OxyContin in 1995 and which has come under fire for failing to respond adequately to safety concerns about the drug, turned down repeated requests to comment on the Sentinel's findings.
Purdue denies its marketing ever put the public's safety at risk.
"Allegations that Purdue's marketing contributed to diversion and abuse are simply not true," said company spokesman Jim Heins, referring to the rerouting of drugs from medical to illegal use. "No evidence has been found to support these allegations."
Purdue executives, battling hundreds of lawsuits and several investigations throughout the country, blame bad publicity on a few criminal doctors and drug abusers who used their pain medication illegally.
In fact, the company says, there are about 2 million patients nationwide being helped by the painkiller. Purdue says no one has ever become addicted to OxyContin when taking it as prescribed.
The Sentinel's investigation, however, found evidence that dozens of oxycodone overdoses in Florida involved patients such as Gerry Cover.
The newspaper launched its inquiry after the Florida Attorney General's Office ended a tobacco-industry-style investigation last year of Purdue's marketing practices.
Officials wondered whether Purdue sales tactics played a role in addiction and abuse tied to the highly profitable pill. Investigators said their efforts didn't turn up anything significant, and they reached a settlement with the company. Their probe focused on the marketing. They did not examine the autopsy reports.
The yearlong investigation ended Nov. 1, when Florida Attorney General Bob Butterworth signed an agreement promising never to sue Purdue for any actions up to that point. Purdue pledged $2 million toward a prescription-tracking program that has failed to gain legislative approval.
Butterworth and one of his assistants who helped in the probe, Dave Aronberg, acknowledged that their enthusiasm was dampened by calls from pain patients who feared the drug might be pulled from the market and by an online poll that showed little support for a lawsuit.
Deaths from OxyContin
In its research, the newspaper examined 500 autopsy reports from across Florida, reviewed more than 5,000 pages from the state's inquiry and interviewed scores of health-care professionals, law-enforcement officers, OxyContin patients, addicts and drug-rehabilitation experts.
The Florida Department of Law Enforcement tracks drug-related deaths based on toxicology tests performed during autopsies. Everyone from doctors to law-enforcement officers follows deadly drug trends outlined in semiannual reports.
Illegal substances such as heroin once topped the charts. Today, prescription drugs turn up more often than street drugs. Drugs with oxycodone were not tracked as a separate class until 2001, after state officials said they became alarmed about anecdotal reports of OxyContin overdoses.
From Jan. 1, 2001, to Dec. 31, 2002, Florida's 24 medical-examiner districts reported that oxycodone overdoses caused 573 deaths. But because oxycodone is available in almost 60 medications, no one knew which specific painkillers were involved in the overdose deaths.
To find out, the Sentinel obtained copies of the 500 autopsy reports in the 573 overdose cases. Some deaths are still under active law-enforcement investigation and autopsy results were not public record. The newspaper also reviewed hundreds of police records and talked to relatives or witnesses to identify the pain medication involved.
The key findings:
Oxycodone was more deadly than heroin during 2001 and 2002 in Florida. The 573 deaths reported as caused by oxycodone overdoses compare with 521 deaths caused by heroin overdoses during the same period.
The most recent statistics publicly available, from 2000, show OxyContin accounted for 25 percent of the market for oxycodone prescriptions. But the Sentinel's research showed OxyContin was the drug identified in about 83 percent of the 247 cases linked to a specific medication. In the remaining 253 oxycodone deaths, the Sentinel did not determine a brand-name drug.
The Sentinel review of the 500 oxycodone deaths found 87 people who had a history of back pain, 19 who were recuperating from surgery and 157 others with health conditions that included arthritis, AIDS, cancer and car-crash injuries. By contrast, 38 cases could be identified in which users had no health issues beyond recreational-drug abuse.
Purdue has directed drug-education efforts mostly toward teenagers. But the average oxycodone overdose victim is 40 years old, the autopsy reports show. And white, middle-aged men between ages 30 and 60 -- many with back pain or other medical problems -- accounted for 254 oxycodone deaths.
Purdue officials would not comment on the details of the Sentinel's autopsy review, referring instead to the company's own study of more than 1,000 "drug-abuse deaths" nationwide involving oxycodone from 1999 to 2002. That study, published in March, found only 30 of the deaths involved oxycodone alone, and only 12 of those were specifically tied to OxyContin.
The newspaper's approach differed from the Purdue study in many ways. One key difference: The Sentinel pinpointed cases in which medical examiners had determined oxycodone to be the cause of death, not simply "involved." And Purdue's study relied on a scattershot sampling of cases from 23 states, not a comprehensive review of a single category of overdoses in one state.
Behind the paper trail and the statistics are countless heartaches for people such as Mary Brady and Larry Jones.
Brady's husband, Doug, 39, enjoyed restoring a 1968 Camaro when the disabled dad wasn't looking after the couple's two school-age children. He died from an OxyContin overdose Aug. 14, 2001. Police said it appeared he took the pills as directed.
Jones said his wife, Grace, 48, loved taking her grandchildren to yard sales on weekends. She took OxyContin for back pain and died from an overdose of the drug March 24, 2002.
"When you've been together for over 20 years, you think you're going to be together forever," Jones said.
Marketing a 'wonder drug'
One of the more significant accomplishments of the Butterworth investigation was securing the 5,000 pages from Purdue to help determine whether the company's promotion of OxyContin played a part in overdose deaths and abuse of the drug.
Among the stacks of documents were clinical trials testing OxyContin's benefits and safety, eight years of marketing plans, hundreds of reports detailing problems that patients had with OxyContin and complaints from a former employee that the company used unauthorized marketing material.
After Florida's investigation was halted, Purdue fought to keep its marketing plans private, citing trade secrets. But the Sentinel went to court to make them public, and a circuit judge in Broward County agreed. The documents open a window into the private company's business.
When Purdue launched OxyContin in 1996, it was considered a new "wonder drug" for cancer patients because it quickly eased their pain and, by many accounts, promised fewer side effects. While OxyContin was first marketed primarily to cancer patients, Purdue's marketing plans show that company officials realized early on that the drug would be more profitable if prescribed to nonmalignant patients.
As use of the drug spread to the general population, it became increasingly available to doctors unfamiliar with its potency and, worse, to some physicians who profited from patients abusing it.
Historically, strong opioid painkillers that had high potential for abuse and addiction, including morphine and hydromorphone, were reserved mainly for cases of severe pain caused by cancer or life-ending conditions.
But the FDA had approved OxyContin for "moderate to severe pain." That opened the door for Purdue to market its use for a much wider class of patients with lesser ailments.
One of the pain experts who had pushed for broader use of opioids was Dr. J. David Haddox, who served from 1995 to 1996 as president of the American Board of Pain Medicine. In 1996, when Purdue began marketing OxyContin, Haddox led a joint task force that produced watershed guidelines encouraging the use of opioids in treating chronic pain.
Haddox joined Purdue in 1999 and is now the company's senior medical director of health policy. After he arrived, the company continued to distribute thousands of videos titled "From One Pain Patient to Another" that claimed less than 1 percent of patients taking opioids became addicted.
The marketing plans are an extension of the confidence that opioids could be used safely for a variety of conditions. The 1997 plans state: "OxyContin will be launched into the nonmalignant pain market. The most common diagnoses for nonmalignant pain are back pain, osteoarthritis, injury and trauma pain."
Sales took off, and so did the available dosages as Purdue added 80- and 160-milligram tablets in addition to its 10-, 20- and 40-milligram tablets. By 1998, two out of three OxyContin prescriptions were written for noncancer pain. The sales goal that year was $220 million, followed in succeeding years by $493 million and $922 million.
Federal records show that between 1996 and 2000, prescriptions for other opioids, such as morphine, Vicodin and Dilaudid, increased by 23 percent. OxyContin prescriptions rose by almost 2,000 percent.
The 2001 sales goals were to generate $1.4 billion in sales, which Purdue surpassed, and to be among the top 10 pharmaceutical companies by 2010. Purdue's records show that more than 40 percent of OxyContin patients had not used opioids previously.
Some critics, including pain-management specialists who advocate the use of opioids, question why patients with such ailments as minor back pain, arthritis and headaches were ever prescribed a painkiller as powerful as OxyContin.
Dr. Marc Gerber, an Orlando pain specialist who prescribes OxyContin, said the opioid should be used only after less-addictive therapies have been tried.
"An opioid is not going to cure everything," Gerber said. "A lot of times, chronic patients just want an ear to listen."
But the use of OxyContin has become so common that it is having a major impact on health-care and workers-compensation costs. The Medicaid program in Florida pays out more than $30 million a year for OxyContin prescriptions, placing it fourth among all pharmaceuticals in Medicare.
Hartford Financial Services Group, one of the nation's largest workers-compensation carriers, said its study showed OxyContin is the most-prescribed drug, accounting for 10 percent of total pharmacy charges.
The doctors' role
It is widely acknowledged in the medical community that doctors often have little education about pain management, narcotics and addiction. Purdue's marketing plans show the company tried to fill that vacuum of knowledge as it encouraged rank-and-file doctors to prescribe OxyContin for a range of ailments.
Kathryn Weiner, executive director of the American Academy of Pain Management in Sonora, Calif., said that even with awareness about complexities of treating pain, most medical schools have failed to change their programs.
"If you miss the three hours they spend on pain management, you've missed the entire curriculum," she said.
Purdue set itself up as a source of knowledge, records show. It armed its sales force with sophisticated data pinpointing a wide range of doctors, including family physicians, who sometimes had little experience in dealing with powerful narcotics.
The Florida investigative files show Purdue sales representatives and the company's advertising made appealing claims. They told doctors OxyContin was less likely to be abused or cause addiction because of its continuous 12-hour relief.
The sales force reinforced those ideas with marketing giveaways that critics claimed were directed at consumers -- which would be a violation of guidelines set by the pharmaceutical and health-care industries.
One of the items was a compact disc of big-band music featuring an elderly couple dancing over the OxyContin logo; another was a video of pain-patient testimonials.
Hundreds of doctors were flown on expense-paid trips to resorts across the country where they were promised speakers' fees if they encouraged other doctors to use OxyContin. While common practice for many drugs, such efforts were unusual for Schedule II narcotics, which have a high potential for abuse.
Purdue's documents show doctors also were told there was no "ceiling," or limit, on doses. Unlike its oxycodone competitors, OxyContin does not contain aspirin or acetaminophen, which could cause stomach and liver problems.
Purdue said a patient's previous opioid use, pain-assessment needs and ability to tolerate a medication determine appropriate dosage. OxyContin's package insert states, "There is no defined maximum dose; the ceiling to analgesic effectiveness is imposed only by side effects, the more serious of which may include somnolence and respiratory depression."
While many doctors unwittingly bought into Purdue's claims in good faith, there are a few who have unscrupulously used OxyContin to boost the number of patients making office visits, and hence profits. But law-enforcement officials say it takes only a few bad doctors to create large pockets of addicts.
A number of Florida doctors who were among Purdue's top subscribers found themselves behind bars. A Panhandle doctor became the first in the country to be convicted of manslaughter by overprescribing OxyContin. Other doctors in Florida have been charged with murder or drug trafficking.
Dr. Sarfraz Mirza, who ran the We Really Care Clinic in Melbourne, was arrested July 29 on 11 counts of trafficking OxyContin. Investigators said they are looking into the possibility that up to eight patients may have died from overdoses.
Purdue under attack
The Sentinel study showing OxyContin was identified in 205 deaths in Florida during a two-year period comes at a time of intensifying controversy about Purdue's "wonder drug." Reports of deaths blamed on OxyContin extend from Key West to Seattle, and hundreds of consumers have sued the drug maker.
The most recent shot came from someone formerly inside the company.
In July, one of Purdue's former top researchers, Marek Zakrzewski, sued the company, alleging it had tried to cover up defects in OxyContin that may have led to addiction and fatal overdoses. Zakrzewski said he was fired in May, a month after he went to the FDA to report his concerns.
Zakrzewski, who had been hired as an assistant director in July 2000, stated in court records that he discovered inconsistencies in OxyContin that caused some tablets to dissolve more quickly than others.
"The faster form could potentially dissolve more quickly into the human body than expected and cause overdosing and potentially lead to addiction," he stated in the lawsuit.
Zakrzewski said company officials told him not to share his concerns about OxyContin because Purdue "did not want problems with" the FDA. In an amended complaint filed Oct. 7, he named 17 Purdue officials who were told about irregularities, including the allegation that some OxyContin was unstable "when exposed to increased humidity or the passage of time."
The lawsuit mentions other concerns, including inaccurate testing methods, refusal to adhere to FDA specifications and problems with alcohol used in making OxyContin. The alcohol, critical to controlling the release rate of the drug, was previously the subject of a warning letter to Purdue from the FDA. As a result of the November 2001 letter, Purdue pulled 388 lots of the tablet from the market.
In interviews, Purdue officials called Zakrzewski's claims "absolutely without merit" and said the company expects to show they are baseless "if and when this case goes to trial."
But the company may have still more questions to answer on Oct. 27, when the U.S. General Accounting Office releases the results of its investigation into whether Purdue's marketing practices contributed to drug abuse and addiction.
Meanwhile, Purdue is set to launch another painkiller that is 10 times more powerful than morphine. Purdue's Palladone, which the FDA reviewed in September, is a time-released version of hydromorphone, sold under the brand name Dilaudid. A drug-enforcement official called Dilaudid "the drug of choice for addicts."
The FDA is weighing the drug's potential for abuse before making a final decision. OxyContin was approved before consideration of abuse potential was required.
1 family's story
Gerry Cover, the Osceola County man who sought relief for an aching back, never intended to become an addict.
In March 2000, Cover and his wife went to a new doctor in Celebration. For the first month, Sylvia Cover said, the doctor prescribed codeine, a narcotic her husband had tolerated well in the past. On the second visit, she said, the physician prescribed 40-milligram OxyContin tablets twice a day. Cover said the doctor reassured them OxyContin was safe.
Within days, Gerry Cover became a changed man, his family said. The self-employed construction manager, who rarely took a day off, began spending most of his time in bed. He complained that he could not last the full 12 hours before taking another pill. So he ran out before the end of the month.
Sylvia Cover said her husband became disoriented and confused, forgetting conversations and dates. He was obsessed with counting pills. He made sure his OxyContin was always close at hand, fearing the horrendous withdrawal symptoms that might kick in otherwise.
On Sept. 19, 2000, it looked as though the Covers' lives were turning around.
Gerry Cover was seeing a pain-management specialist who was helping him reduce his medication to 20-milligram doses. Just what happened that night might never be fully known. Sylvia Cover and her son Gerry Jr., 18, were watching television while Gerry Sr. was napping. Sylvia checked on her husband and heard him snoring.
When she returned a little later, she found him blue and cold. An autopsy determined that he had a lethal dose of oxycodone.
Cover's death left his wife and children emotionally and financially devastated, and they are suing Purdue Pharma. Foreclosure of their modest home hangs over their heads.
Last Christmas, Sylvia Cover made a homemade card for her son. Inside was an IOU until the day comes she can afford to buy a present.
"Our house used to always be full of family and friends," she said. "We even had a party for Groundhog Day.
"But I no longer have a life."
Doris Bloodsworth can be reached at [email protected] or 407-420-5411.
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