Reformulation of OxyContin to make it abuse-deterrent is main reason for shift to heroin and deaths from it, study concludes

By Melissa Patrick
Kentucky Health News

The reformulation of  OxyContin in 2010 is the main reason for the large increase in heroin overdose in recent years, according to a working paper by the RAND Corp. and the Wharton School of economics at the University of Pennsylvania.

Purdue Pharma released OxyContin as a 12-hour-release opioid for acute or chronic pain in 1996. The original formulation could be easily crushed or dissolved, allowing a person to get the 12-hour dosage all at once, making it ripe for abuse.

In 2007, Purdue Pharma pleaded guilty to misleading consumers about the risk of abuse associated with the drug and paid $600 million in federal fines. In 2010, it released a new formulation of OxyContin that made it "abuse-deterrent," the first drug to get this designation from the Food and Drug Administration. The report says the formula reduced non-medical OxyContin use as much as 40 percent.

This effort, along with prescription-monitoring programs and "pill mill" laws in Kentucky, Florida and other states, have all been credited with reducing prescription-painkiller deaths, but also the increase in the abuse of "substitute" opiates such as heroin and fentanyl.

Click on chart to see a larger version of it

Kentucky has one of the highest OxyContin misuse rates in the nation, at 0.97 percent, says the report. To combat this, the state instigated the Kentucky All-Schedule Prescription Electronic Reporting (KASPER) system and passed a pill-mill bill in 2012 that put additional restrictions on pain clinics and requires people who have certain controlled-substance prescriptions to submit to a regular urine test.

In 2015 Kentucky had 1,220 total overdose deaths, with 605 of them from prescription opioids and 289 from heroin. Five years earlier, 538 of the 996 total overdose deaths were from prescription opioids and only 34 from heroin, according to the Kentucky Injury Prevention and Research Center.

The study, statistically controlling for the monitoring programs and pill-mill laws, concluded that the reformulation of OxyContin played a larger role in the shift to heroin, accounting for "as much as 80 percent of the three-fold increase in heroin mortality since 2010," the study report says.

Researchers based their conclusion on the differences in heroin deaths after 2010 in states that had differing rates of OxyContin abuse before then.

"States with the highest initial rates of OxyContin misuse experienced the largest increases in heroin deaths," they write. "Results show that this differential increase in heroin deaths began precisely in the year following reformulation."

It also found that prior to 2010, there was no correlation between OxyContin abuse and heroin deaths. "Both the levels and trends in heroin deaths were nearly identical across states with high or low initial rates of OxyContin misuse before 2010," the study report said.

Graph is from the report, deaths per 100,000
 Data from the National Vital Statistics System

The study found that after the OxyContin reformulation in 2010, prescription opioid abuse and overdose deaths from them in the U.S. decreased for the first time since 1990, but this drop coincided with "an unprecedented rise in heroin overdoses," which "more than tripled between 2010 and 2014 (from 1.9 to 3.4 deaths per 100,000)." Heroin was responsible for the deaths of more than 10,000 Americans in 2014.

"Each percentage-point reduction in the rate of OxyContin misuse due to reformulation leads to 3.1 more heroin-related deaths per 100,000," the study report said. It also said the "impact of the reformulation on heroin and opioid deaths largely offset each other, leading to no net reduction in overall overdose deaths."

The study concluded that "supply-side strategies," like creating abuse-deterrent drugs, as the FDA is actively encouraging, or making it harder for patients to gain access to them, won't solve the nation's drug problems. However, it said they could deter new abuse: "Treating underlying demand may prove to be the more effective strategy for dealing with the current opioid epidemic, particularly because substitutes are readily available."

Data for the report, published by the National Bureau of Economic Research, is from the National Survey on Drug Use and Health and the National Vital Statistics System.

OxyContin sales reps used food, gifts to convince doctors to buy drugs, says investigative report

Pharmaceutical sales representatives from health-care giant Abbott Laboratories sales reps "were instructed to downplay the threat of addiction with OxyContin and make other claims to doctors that had no scientific basis," David Armstrong reports for Stat, the health-and-medicine supplement to The Boston Globe, after reading internal documents in a lawsuit that were unsealed by a judge.

The documents revealed that offering sugary sweets was the secret to getting one surgeon to listen to sales pitches for OxyContin, and to buy the painkiller, according to internal documents obtained by Using a tip from nurses that the surgeon liked junk food, the sales rep "showed up with a sheet cake box filled with doughnuts and snack cakes arranged to spell out the word 'OxyContin'," Armstrong reports. (Stat photo illustration)

"The doughnut ploy . . . shows the lengths to which Abbott went to hook in doctors and make OxyContin a billion-dollar blockbuster," Armstrong writes. "The sales force bought takeout dinners for doctors and met them at bookstores to pay for their purchases. In memos, the sales team referred to the marketing of the drug as a 'crusade,' and their boss called himself the 'King of Pain'.”

What Armstrong calls "a treasure trove of internal documents" became available a few months ago, when a Kentucky judge ordered their release in response to a motion by Stat, reported Kentucky Health News, published by the Institute for Rural Journalism and Community Issues, which also publishes The Rural Blog: "Documents were part of a state attorney general's lawsuit settled in December by payment of $24 million from Purdue Pharma, the maker of OxyContin."

Armstrong writes, "Abbott, a much larger company than Purdue, had a sales force entrenched in hospitals and surgical centers, and had existing relationships with anesthesiologists, emergency room doctors, surgeons, and pain management teams. Abbott devoted at least 300 sales reps to OxyContin sales—about the same number of people Purdue initially dedicated to the drug—as part of a co-promotional agreement with Purdue."

Abbott marketed OxyContin from 1996 through 2002 after it was approved by the U.S. Food and Drug Administration, Armstrong writes. "With Abbott’s help, sales of OxyContin went from a mere $49 million in its first full year on the market to $1.6 billion in 2002. Over the life of the partnership, Purdue paid Abbott nearly a half-billion dollars, according to court records." (Read more)

Rogers, other drug-caucus chair file bill to reverse FDA's approval of new painkiller; competing company has alternative

Illustration from PainAndDepression.com

U.S. Reps. Hal Rogers of Somerset and Stephen Lynch of Massachusetts have introduced a bill to withdraw federal approval of a new formulation of hydrocodone that is highly addictive and produced in crushable pills, which they say threatens to start a new wave of prescription drug abuse. They are the Republican and Democratic co-chairs, respectively, of the Congressional Caucus on Prescription Drug Abuse.

But the Food and Drug Administration might act against Zohydro ER on its own, because Purdue Pharma LP has completed testing of a competing, non-crushable drug and will ask for "a priority review that would cut two to three months off the 10 months the agency sets as a goal to examine applications" for regulatory approval, Drew Armstrong of Bloomberg News reports. "Purdue’s pill is hard to crush and snort or inject."

That is important to the FDA. “If and when they, or another manufacturer, are able to create an abuse-deterrent formulation that remains safe and effective for patients, we would certainly give serious consideration to assuring that any non-abuse formulations are removed from the market,” FDA pain-drug director Bob Rappaport said in his Oct. 25 review of Zohydro’s approval.

Zohydro ER is an extended-release hydrocodone medication made by Zogenix Inc. for patients who need round-the-clock, long-term pain treatment and have found other treatments to be inadequate. Unlike recent formulations of the popular painkillers OxyContin and Opana, is not crush-resistant, but the company has said it is working on a crush-resistant version.

Citing concerns about abuse, the FDA's scientific advisory panel voted 11-2 against approving Zohydro ER, and a coalition of more than 40 health, consumer and other organizations urged the FDA to revoke its approval. Attorney General Jack Conway was among 28 attorneys general who sent the FDA a letter asking it to reconsider. Sen. Joe Manchin, D-W.Va., has introduced a companion bill to the one filed by Rogers and Lynch.

Hal Rogers (Associated Press photo)

Rogers said in a press release, "“While the FDA continues to send mixed signals to drug companies about the need to invest in abuse deterrent technologies, the Act to Ban Zohydro will make it abundantly clear – life saving measures are critical to the development of powerful painkillers like Zohydro. . . . In Southern and Eastern Kentucky, we lost nearly an entire generation when crushable OxyContin was first prescribed, and I fear this crushable, pure hydrocodone pill will take us backwards with a new wave of addiction and tragic, untimely deaths."

Kentucky ranks third in the nation for overdose deaths, with more than 1,000 Kentuckians dying each year from prescription drug overdoses. The number has leveled off following passage of laws that target pill-pushing clinics and doctors, and put stricter regulations on painkillers.

Zogenix has said it is committed to exceeding FDA requirements to make sure the drug is used appropriately, will monitor for misuse, and will allow an outside group to monitor and analyze its data. It noted that Zohydro ER will be regulated as a Schedule II drug, which means it can only be dispensed through a physician’s written prescription, with no refills, and does not contain acetaminophen, longtime use of which can cause liver failure.

Beshear, Stumbo credit law for reducing prescription-drug deaths, but reduction was far outnumbered by rise in heroin fatalities

UPDATE: Final, revised data show that prescription-drug deaths in Kentucky actually increased slightly, from 1,022 in 2011 to 1,031 in 2,012, according to the Kentucky Injury Prevention and Research Center. Heroin-related deaths rose from 42 in 2011 to 129 in 2012, a smaller increase than preliminary data showed but still a rise of 307 percent.

Deaths from prescription-drug abuse in Kentucky declined last year for the first time in a decade, and top state officials are crediting a law passed by that year's General Assembly.

However, passage of the law has prompted many drug users to switch to heroin, and the increase in heroin deaths (121) was much larger than the decline in prescription-drug fatalities (19).

"Autopsied overdose deaths attributed to the use of heroin increased 550 percent over the previous year, from 22 in 2011 to 143 cases in 2012," a release from Gov. Steve Beshear's office said. The decline in prescription-drug deaths was 1.9 percent, from 1,023 to 1,004, but the release said nothing else about the new problem and did not link it to the 2012 law that cracked down on abuse of prescription drugs.

“The impact of this bill can’t be measured just in the numbers of pills we’ve kept off the streets,” Beshear said in the release. “This bill, I believe, has literally saved lives in Kentucky.”

House Speaker Greg Stumbo, D-Prestonsburg, said, “I’m proud of the results, and the fact that other states are following our lead. Our goal now is to build on these gains and to improve access to treatment, so that abusers can truly escape this deadly cycle once and for all.”

The first quote in John Cheves' Lexington Herald-Leader story came from Van Ingram, executive director of the state Office of Drug Control Policy, which the new law required to begin publishing annual reports on drug overdose fatalities in the state: "There's no great victories here. I'm glad that we're at least seeing a leveling off and some small decline. I've been in this job for nine years and have watched a steady rise in numbers that whole time."

Top counties: Leslie, Clinton, Clay, Estill, Floyd, Nicholas, Perry, Whitley, Monroe (Herald-Leader)

The law, known as House Bill 1 before Beshear signed it, required pain-management clinics to be owned by a licensed medical provider, required all drug prescribers to register with a state monitoring system, and reduced the number of prescriptions for heavily abused controlled substances, a release from the governor's office said.

"Since the law was passed, 20 non-physician-owned pain management facilities have closed," the release said. The "Cabinet for Health and Family Services has issued cease-and-desist letters to another four pain management facilities operating outside the scope of state regulations."

"Of the 1,004 overdose fatalities in 2012, 888 were found to be unintentional, 59 were suicides and 57 remain undetermined," the release said. "Alprazolam (Xanax) remained the most-detected controlled substance in overdose deaths, present in 41 percent of all autopsied cases. Morphine was found in 32 percent of autopsies, followed by hydrocodone at 26 percent and oxycodone at 24 percent."

"Autopsies often found more than one drug present," Cheves notes. "The youngest overdose fatality was 16; the oldest was 72. Slightly more than half of the victims were men. Leslie County (population 11,170) reported the state's top per-capita rate of an annualized 85 fatal overdoses for every 100,000 people. The county had 11 overdose deaths in 2012, up from eight the previous year. In descending order, the other leading counties were Clinton, Clay, Estill, Floyd, Nicholas, Perry, Whitley, Monroe and Magoffin." (Read more)

Read more here: http://www.kentucky.com/2013/07/26/2734183/kentucky-drug-deaths-decline-slightly.html#storylink=cpy

Deaths by overdose, mainly of prescription drugs, hit a new record in U.S. in 2011; a huge problem in Kentucky

Drug overdose deaths in the U.S. rose for the 11th straight year and accidental deaths involving addictive prescription drugs overshadow deaths from illicit narcotics, new federal data show.

In 2010, there were 38,329 drug overdose deaths nationwide, and prescription drugs were the cause of nearly 60 percent of them.  As in recent years, opioid drugs such as OxyContin and Vicodin were the biggest problem, contributing to three-fourths of medication-overdose deaths, report Lindsey Tanner and Mike Stoppe of The Associated Press.

Anti-anxiety drugs including Valium were involved in almost 30 percent of medication-related deaths.  Most were unintentional overdoses; 17 percent were rules suicides. The data were reported Tuesday in the Journal of the American Medical Association.

In Kentucky, drug abuse is epidemic and more than 1,000 Kentuckians a year die from prescription-drug overdoses, more than the number who die in car accidents, according to a 2012 Kentucky Justice & Public Safety Cabinet report. About 85 percent of Kentucky's drug-related deaths were accidental and approximately 2 percent were suicides, according to federal Centers for Disease Control and Prevention data.

The number of drug-overdose deaths in Kentucky rose a staggering 296 percent from 2000 to 2010. In 2010, the record number of deaths reflected the national trend and also involved opioid painkillers, according to a study by the Kentucky Injury Prevention and Research Center. The highest rates of overdose deaths during the study period were concentrated in Eastern Kentucky and among men, reports Bill Estep of the Lexington Herald-Leader.

Many doctors and patients don't realize how addictive these prescription drugs can be, and that they're too often prescribed for pain that can be managed with less risky drugs, said Dr. Thomas Frieden, head of the CDC. He said the data show a need for more prescription drug monitoring programs at the state level, and more laws shutting down "pill mills" -- doctor offices and pharmacies that over-prescribe addictive medicines, AP reports.

That was the aim of House Bill 1, passed in last year's legislative session. The Kentucky All-Schedule Prescription Electronic Reporting  (KASPER) system has undergone several changes since the bill's passage to help crack down on so-called pill mills.

Last month, a federal panel of drug safety specialists recommended that Vicodin and dozens of other medicines be placed in a more restrictive drug category, which would make them harder to prescribe. Refills wouldn't be allowed without a new prescription, and faxed or called-in prescriptions wouldn't be accepted; only a handwritten prescription from a doctor would be allowed.

Kentucky's pill-mill problem and law to fight it get national airing, with issues of patient privacy versus public health debated

Kentucky's "pill problem" went more public Thursday when David Hopkins, head of the state's prescription drug monitoring program, told the National Conference of State Legislatures the true extent of our prescription pain pill addiction. Maggie Clark of Stateline reports that lawmakers "shook their heads in disbelief" when Hopkins said the state's doctors issued 60 million prescriptions for the 4.4 million Kentuckians in August of this year alone. The stark admission was a way to start talking about where patient privacy ends and public health concerns begin, Clark writes.

Kentucky is among 42 states with operational prescription-monitoring laws but few others require physicians to use the database to chronicle each patient and their drug use before prescribing as Kentucky does. And while the commonwealth allows its law-enforcement officers access to the database, the database is not controlled by the attorney general's office but, as a nod to patient privacy, by the Cabinet for Health and Family Services. In Vermont, legislators fought that battle earlier this year, with police there needing a warrant to access it. When Kentucky's law enforcement officers were surveyed about the law in 2010, 73 percent said they found the tool "excellent" for obtaining evidence.

At the conference, a report citing a Centers for Disease Control review explained that data collected through 2005 in a limited number of studies shows that having a prescription drug monitoring program in place had no clear impact on overdose mortality, Clark reports.

Cheaper heroin showing up in Eastern Kentucky as crackdown on pain pills makes that trade less attractive

About 60 grams of heroin, worth about
$8,000. (AP photo)

It was only few months ago that Northern Kentucky law enforcement officers and substance abuse clinics began expressing grave concern that heroin was fast becoming the go-to drug in their region. Today, there are signs that the drug is already moving swiftly east, into the already drug-ravaged mountains of Eastern Kentucky. The reason for the uptick in heroin use? Because pain pills aren't as available anymore.

Federal and state law enforcement have been cracking down on the prescription pain-pill drug trade for years in these parts. They've created electronic prescription-tracking systems, staked out pain management clinics and shut down a drug pipeline that starts in Florida. Some argue that last year's passage of House Bill 1 has discouraged even legitimate doctors from prescribing pain drugs. All these things make heroin usage an unintended consequence of their success, officials fear.

 "There's always some type of drug to step up when another gets taken out," Dan Smoot, law enforcement director of Operation UNITE, which handles drug investigations in 29 Eastern Kentucky counties, told Brett Barrouquere of The Associated Press. "We didn't know it was going to be heroin. We knew something was going to replace pills."

Officials say the heroin is trafficked from Mexico into the U.S., where it first goes to Illinois, Michigan and Ohio. Northern Kentucky counties have been the epicenter of heroin abuse in the state, but law enforcement officials in Louisville, Lexington and Appalachian counties are reporting "a dramatic rise in the number of arrests and seizures related" to heroin. Kentucky State Police seized 11 doses of heroin and other opiates in 2008 in the eastern half of the state; they have seized 395 doses there so far this year.

Users are attracted to heroin's low cost compared to pain pills, Barrouquere reports. A single oxycodone pill can cost from $80 to $100, but heroin can cost as little as $15 to $20 for an amount that will produce the same level of intoxication as one pain pill for 24 hours, Kentucky Office of Drug Control Policy Director Van Ingram said. (Read more)

New form of Oxy is harder to inhale and inject, so drug users are turning to heroin, Opana for high

A new formulation of OxyContin makes it harder to
inhale or inject. Drug Enforcement Administration photo.

A change in the formulation of the powerful drug OxyContin has addicts turning to another high to fuel their habit: heroin.

Researchers at the Washington University School of Medicine in St. Louis had more than 2,500 patients from 150 drug rehabilitation treatment centers in 39 states respond to survey questions that had a particular focus on the reformulation of OxyContin, reports research-reporting service Newswise. The new formula makes it harder to crush the pills, making inhaling or injecting them more difficult.

Since the new version of the drug was introduced, "inhalation or intravenous administration has dropped significantly," said lead investigator Theodore J. Cicero. But drug use has not lessened, with addicts turning to heroin instead, which is also inhaled or injected. "We're now seeing reports from across the country of large quantities of heroin appearing in suburbs and rural areas," Cicero said.

OxyContin was originally designed to be released in the body slowly, preventing an immediate high. But by crushing the pills and inhaling them or dissolving them in water and then injecting the solution, addicts were able to get "an immediate rush," Newswise reports.

Moreover, because OxyContin was designed to be slow-release, it contained large amounts of the generic drug oxycodone, which spurred even more in demand. The new version of the drug was introduced in 2010.

Survey results show "users who selected OxyContin as their primary drug of abuse has decreased from 35.6 percent of respondents before the release of the abuse-deterrant formulation to 12.8 percent now," Newswise reports. (Read more)

The Centers for Disease Control and Prevention has called prescription drug abuse an "epidemic." In Kentucky, about a 1,000 people die each year from prescription drug overdoses. More people die in Kentucky from prescription drug overdoses than they do from traffic accidents.

Law enforcement is also seeing that drug seekers are switching from OxyContin to the prescription drug Opana, reports Donna Leinwand Leger for USA Today. "A few years ago, it was OxyContin. Now it's Opana," said Raquel Foster, a police spokeswoman for the Fort Wayne Police Department.

As a new, harder-to-abuse formulation of Opana hits the market, however, "they are going to find a way to satisfy their addiction," said DEA Special Agent Gary Boggs of the Office of Diversion Control. "When they either can't get those particular pharmaceuticals or can't afford them, they now gravitate to heroin."  (Read more)

Prescription pill abuse 'a holocaust' in Kentucky, hitting 1 in 16; big drug firms and even well-meaning doctors are to blame

Another in-depth look at Kentucky's prescription drug abuse problem hit the pages of The Courier-Journal yesterday, this time exploring the history of OxyContin and how well-meaning doctors started over-prescribing opioids in the 1990s in response to vigorous marketing campaigns. 

The problem continues to be gargantuan, with Laura Ungar reporting about one in 16 Kentuckians misused prescription painkillers in the past year. Kentucky ranks "as the fourth-most-medicated state in a nation that fills enough painkiller prescriptions each year to keep every American adult medicated around the clock for a month," Ungar writes.

A review published in the journal Pain Physician last year found evidence is lacking for how effective opioids are in treating long-term pain. "They're not M&Ms," said Dr. Lee Tannenbaum, founder of the Bel Air Center for Addictions in Maryland. "As physicians, we need to be really, really, really careful as to when we put someone on these drugs. Cancer pain may need opioids, but someone out shoveling snow who hurt his back doesn't. We have created so many addicts."

A C-J investigation found physicians fuel the problem in three ways. First, they do not screen patients adequately. They prescribe powerful pills for moderate pain. And they do not use the state's monitoring program, Kentucky All Schedule Prescription Electronic Reporting, known as KASPER.

The problem started in the 1990s when "medical organizations, concerned that pain wasn't being treated adequately, encouraged doctors to do more to relieve suffering," Ungar reports. OxyContin was approved by the Federal Food and Drug Administration in 1995, with OxyContin prescriptions for noncancer pain increasing by tenfold between 1997 and 2002. A report found the drug's maker, Purdue Pharma "directed its drug representatives to focus on physicians in their sales territories who were high opioid prescribers, while also issuing OxyContin 'starter coupons' for patients and distributing promotional items, such as fishing hats and plush toys," Ungar reports.

In October 2007, Kentucky and Pike County sued Purdue Pharma for its deceptive marketing campaign, alleging it misled doctors about the potency of the drug, which is twice as powerful as morphine. U.S. Rep. Harold "Hal" Rogers, R-5th District, called OxyContin "the guilty party that got this epidemic going." In Kentucky, the retail distribution of oxycodone grew from 83,000 grams in 1997 to 950,000 grams in 2010.

Part of the problem is that doctors do not have the time they need to properly assess patients for potential abuse. "You've got an awful lot of doctors prescribing not out of ill intents. They've got a limited amount of time, and pain patients require a lot of time," said Robert Walker, assistant professor of behavioral science at University of Kentucky's Center on Drug and Alcohol Research. "The easiest solution is the opioid."

While easy, they are not necessarily effective for all pain. Evidence is "very, very mixed" on whether the drugs work in the long term on chronic pain and "the evidence is pretty scant" that they are effective against treating chronic lower back pain, said Dr. Timothy Ives of the University of North Carolina.

Though the problem is never expected to be solved completely, there are steps being taken to combat the issue. In 2010, the FDA approved a reformulation of OxyContin which makes it more resistant to being cut, chewed, crushed or dissolved — methods that make the drug more powerful. The Kentucky Board of Medical Licensure has spelled out "the steps physicians need to take as they seek to help patients control pain unrelated to terminal illness," Ungar reports. And the Kentucky General Assembly passed a comprehensive bill that requires doctors to use KASPER when prescribing certain drugs and take a full medical history of patients to whom they are considering prescribing drugs. (Read more)

Prescription pill problem in Kentucky, elsewhere under microscope on NPR program

The growing prescription-drug abuse problem in Kentucky and other states was under the microscope Thursday during National Public Radio's "On Point," hosted by Tom Ashbrook.

The Courier-Journal's Laura Ungar, who wrote an extensive series on pain-medicine abuse this year, was one of three journalists who spoke about the epidemic. Dealers visit various pain-management clinics, which have been labeled "pill mills," fill the prescriptions and then sell the drugs at a high profit.

Ungar, left, called the prescription drug trade "akin to the illegal drug trade, where many of our folks in Kentucky are getting drugs that originated in Florida." Indeed, 98 of the nation's top 100 prescribers of drugs Oxycontin and Xanax are in Florida, the journalists conveyed.

One caller to the show, identified as Michelle of Carter County, Kentucky, shared what it was like when her mother was a pain-meds addict. "We would wake up in middle night and have to put her to bed because she was like a zombie," she said. "It was like no one was there."To read more and listen to the show, click here.