But OxyContin’s stunning success masked a fundamental problem: The drug wears off hours early in many people, a Los Angeles Times investigation found. OxyContin is a chemical cousin of heroin, and when it doesn’t last, patients can experience excruciating symptoms of withdrawal, including an intense craving for the drug.
The problem offers new insight into why so many people have become addicted to OxyContin, one of the most abused pharmaceuticals in U.S. history.
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In a 1992 submission to the Patent Office, the company portrayed OxyContin as a medical breakthrough that controlled pain for 12 hours “in approximately 90% of patients.†Applying for a separate patent a few years later, Purdue said that once a person was a regular user of OxyContin, it “provides pain relief in said patient for at least 12 hours after administration.â€
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Over the last 20 years, more than 7 million Americans have abused OxyContin, according to the federal government’s National Survey on Drug Use and Health. The drug is widely blamed for setting off the nation’s prescription opioid epidemic, which has claimed more than 190,000 lives from overdoses involving OxyContin and other painkillers since 1999.
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OxyContin taken at 12-hour intervals could be “the perfect recipe for addiction,†said Theodore J. Cicero, a neuropharmacologist at the Washington University School of Medicine in St. Louis and a leading researcher on how opioids affect the brain.
Patients in whom the drug doesn’t last 12 hours can suffer both a return of their underlying pain and “the beginning stages of acute withdrawal,†Cicero said. “That becomes a very powerful motivator for people to take more drugs.â€
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Purdue developed OxyContin as a cure for pain — and for a financial problem.
The company’s owners were the Sacklers, a New York family of physicians and philanthropists who bought Purdue in 1952. By the late 1980s, the patent on its main source of revenue, a morphine pill for cancer patients called MS Contin, was running out. Executives anticipated a massive loss of revenue as generic versions drove down the price of MS Contin, according to internal company correspondence from the period.
The company was focused on finding a new moneymaker. In a 1990 memo, Robert F. Kaiko, vice president for clinical research, laid out why it was important to develop a second painkiller.
“MS Contin may eventually face such serious generic competition that other controlledbless-release opioids must be considered,†Kaiko wrote.
Purdue already had developed a technique to stretch a drug’s release over time. In MS Contin, the technique made morphine last eight to 12 hours. Kaiko and his colleagues decided to use it on an old, cheap narcotic, oxycodone.
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Dr. Curtis Wright, who led the agency’s medical review of the drug, declined to comment for this article. Shortly after OxyContin’s approval, he left the FDA and, within two years, was working for Purdue in new product development, according to his sworn testimony in a lawsuit a decade ago.
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By the third year, sales were more than double MS Contin’s peak, according to sworn testimony by a Purdue executive. By the fifth, OxyContin was generating annual revenue of more than $1 billion. Sales would continue to climb until 2010, when they leveled off at $3 billion.
Purdue’s owners, the Sackler family, were already rich — the family name adorns a wing of the Metropolitan Museum of Art and several galleries in the British Museum. The success of OxyContin brought a whole new level of wealth. Forbes magazine last year estimated the Sacklers’ worth at $14 billion, which, the magazine noted, put the family ahead of American dynasties such as the Mellons and Rockefellers.
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In another study of 87 cancer patients, “rescue was used frequently in most of the patients,†and 95% resorted to it at some point in the study, according to a journal article detailing the clinical trial.
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OxyContin’s impact on the practice of medicine was similarly transformative. Other drug companies began marketing their own narcotic painkillers for routine injuries. By 2010, one out of every five doctor’s visits in the U.S. for pain resulted in a prescription for narcotic painkillers, according to a Johns Hopkins University study.
OxyContin accounted for a third of all sales revenue from painkillers that year, according to industry data.
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The U.S. Justice Dept. launched a criminal investigation, and in 2007 the company and three top executives pleaded guilty to fraud for downplaying OxyContin’s risk of addiction. Purdue and the executives were ordered to pay $635 million. The case centered on elements of Purdue’s marketing campaign that suggested to doctors that OxyContin was less addictive than other painkillers.
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Boosting the dosage could extend the duration to some degree, but it didn’t guarantee 12 hours of relief. Higher doses did mean more money for Purdue and its sales reps. The company charged wholesalers on average about $97 for a bottle of the 10-milligram pills, the smallest dosage, while the maximum strength, 80 milligrams, ran more than $630, according to 2001 sales data the company disclosed in litigation with the state of West Virginia. Commissions and performance evaluations for the sales force were based in part on the proportion of sales from high-dose pills.
A West Virginia supervisor told one of his highest performing sales reps in a 1999 letter that she could “blow the lid off†her sales and earn a trip to Hawaii if she persuaded more doctors to write larger doses.
In an August 1996 memo headlined “$$$$$$$$$$$$$ It’s Bonus Time in the Neighborhood!†a manager reminded Tennessee reps that raising dosage strength was the key to a big payday.
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A separate study underwritten by a Purdue competitor, Janssen Pharmaceutica, reached a similar conclusion. Researchers surveyed chronic pain patients treated with OxyContin and reported that less than 2% said the drug lasted 12 hours and nearly 85% said it wore off before eight, according to a 2003 journal article detailing the research.
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While Purdue’s litigators were working in courthouses around the country to fend off civil suits, its regulatory attorneys in Washington, D.C., made a blunt admission to the FDA: The 12-hour dosing schedule is, at least in part, about money.
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Their final reason: It was better for business.
“The 12 hour dosing schedule represents a significant competitive advantage of OxyContin over other products,†the lawyers wrote.
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In the fivebless-minute presentation, Egilman accused Purdue of ignoring its own science for financial reasons and sending patients on a dangerous roller coaster of withdrawal and relief.
“In other words,†he said, “the Q12 dosing schedule is an addiction producing machine.â€
Egilman noted that he had reviewed confidential Purdue documents and sealed testimony of company executives through his work as an expert witness. But, he said, because of court orders sought by Purdue, he was barred from revealing what he’d read in those documents or giving them to the FDA.
