OxyContin’s 12-hour problem — and its central role in the prescription opioid epidemic

During the past two decades, OxyContin has earned its manufacturer, Purdue Pharma, more than $31 billion. But while it was making the company and its owners (the Sackler family) very, very rich, the drug was also becoming one of the most abused prescription drugs in U.S. history.

In fact, many health officials trace the current opioid epidemic in the U.S. to Purdue’s 1996 launch of OxyContin.

The federal government’s National Survey on Drug Use and Health estimates that 7 million Americans have become addicted to OxyContin since it came on the market.

And since 1999, more than 190,000 people have died from overdoses involving OxyContin and other prescription opioids.

Sales of OxyContin took off because Purdue told doctors that one dose would relieve pain for 12 hours — twice as long as the lower-costing generic painkillers available at the time. That would save patients from waking up in the night to take a pill.

The company also broadened the market for the drug, urging doctors to use it not only to treat cancer and the terminally ill, but also for common and often chronic conditions such as backache and knee pain.

But there was a huge problem with that sales pitch, as a team of reporters point out in a disturbing investigative article published Thursday in the Los Angeles Times. For Purdue knew — from its own studies as well as from feedback the company was receiving from doctors — that the painkiller wears off earlier than 12 hours in many people.

And they knew about that dosing problem even before they began selling the drug

Why does that matter? Because OxyContin’s inability to last for the prescribed time is a major factor in its addictiveness.

A long paper trail

For their article, the reporters — Harriet Ryan, Lisa Girion and Scott Glover — reviewed three decades of internal Purdue documents from court cases and government investigations, including many records previously sealed by various courts.

“The documents provide a detailed picture of the development and marketing of OxyContin, how Purdue executives responded to complaints that its effects wear off early, and their fears about the financial impact of any departure from 12-hour dosing,” the reporters write.

Here is their summary of what they uncovered: 

• Purdue has known about the problem for decades. Even before OxyContin went on the market, clinical trials showed many patients weren’t getting 12 hours of relief. Since the drug’s debut in 1996, the company has been confronted with additional evidence, including complaints from doctors, reports from its own sales reps and independent research.

• The company has held fast to the claim of 12-hour relief, in part to protect its revenue. OxyContin’s market dominance and its high price — up to hundreds of dollars per bottle — hinge on its 12-hour duration. Without that, it offers little advantage over less expensive painkillers.

• When many doctors began prescribing OxyContin at shorter intervals in the late 1990s, Purdue executives mobilized hundreds of sales reps to “refocus” physicians on 12-hour dosing. Anything shorter “needs to be nipped in the bud. NOW!!” one manager wrote to her staff.

• Purdue tells doctors to prescribe stronger doses, not more frequent ones, when patients complain that OxyContin doesn’t last 12 hours. That approach creates risks of its own. Research shows that the more potent the dose of an opioid such as OxyContin, the greater the possibility of overdose and death.

• More than half of long-term OxyContin users are on doses that public health officials consider dangerously high, according to an analysis of nationwide prescription data conducted for The Times.

A cousin of heroin

Purdue wants the blame placed on individuals for misusing OxyContin, but as the Times’ reporters point out, it’s the company’s insistence that the drug should be taken only on a 12-hour schedule that has driven many people to addiction.

“OxyContin is a chemical cousin of heroin,” they write, “and when it doesn’t last, patients can experience excruciating symptoms of withdrawal, including an intense craving for the drug.”

And from their own studies, Purdue knew the drug wasn’t lasting 12 hours in many patients. Write the Times’ reporters: 

In study after study, many patients given OxyContin every 12 hours would ask for more medication before their next scheduled dose.

For example, in one study of 164 cancer patients, one third of those given OxyContin dropped out because they found the treatment “ineffective,” according to an FDA analysis of the study. Researchers then changed the rules of the study to allow patients to take supplemental painkillers, known as “rescue medication,” in between 12-hour doses of OxyContin.

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. 

A revolving door

When Purdue was asked by the Times’ reporters to comment, the company sent a written statement in which it pointed out that the Food and Drug Administration (FDA) approved OxyContin as a 12-hour drug.

And that’s certainly true. The FDA did approve OxyContin’s drug application in 1995 as a 12-hour drug. It based that approval primarily on a Purdue-run study that involved 90 female surgical patients in Puerto Rico. 

But the company had to show the FDA only that OxyContin lasted 12 hours for at least half of the patients who take it. The Puerto Rico study did show that — although just barely.

“More than a third of the women [in the study] given OxyContin started complaining about pain in the first eight hours and about half required more medication before the 12-hour mark, according to an FDA analysis of the study,” write the Times’ reporters. 

In defense of its approval of OxyContin as a 12-hour medication, an FDA spokesperson told the Times’ reporters that it’s “well understood” that pain medications will have some variability in the length of their effectiveness and that “physicians should carefully individualize their approach to patients based on how quickly they metabolize the drug.”

The reporters offer an interesting — and troubling — footnote to the FDA’s approval of OxyContin: 

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.

A rapid transformation

Once it was launched, OxyContin quickly — and radically — transformed how doctors treated pain. 

“Other drug companies began marketing their own narcotic painkillers for routine injuries,” write the Times’ reporters. “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.”

“Rates of addiction and overdose have soared alongside the rise in prescriptions,” they add.

In 2007, Purdue and three of its executives pleaded guilty to fraud — and paid $635 million in fines — for downplaying OxyContin’s risk of addiction. But the company has continued to insist that the drug is both safe and effective at 12-hour intervals. It tells doctors that when patients complain about the drug’s effects wearing off earlier, they should prescribe the drug at higher amounts, not more frequently.

Those higher doses are dangerous, however. For, as one expert told the reporters, “The higher you go, the more likely you are to die.”

One Canadian study found that people put on high doses of OxyContin are 24 more times likely to die from opioid-related causes than those put on lower doses.

There’s plenty more disturbing information in this investigative report. Keep it in mind the next time you hear a politician, pundit or anyone else blaming our current, tragic epidemic of drug addiction on a lack of “values and principles.” Whose values? Whose principles?

FMI: You can read the L.A. Times report in full on the newspaper’s website.