Fast-Acting Opioids Get New Boxed Warning - FDA strengthens risk labeling for drugs such as Vicodin
The FDA is updating the labels on immediate-release opioids like Vicodin with new boxed warnings, and an indication for use only in the most severe pain, the agency announced.
The boxed warning alerts prescribers to the risk of misuse, abuse, addiction, overdose, and death associated with the drugs, as well as the risk of neonatal opioid withdrawal syndrome (NOWS) if taken during pregnancy.
The new indication also reserves the drugs for pain "severe enough to require opioid treatment" that doesn't respond to other therapies.
The agency is also updating label safety information on both immediate-release (IR) and extended-release/long-acting (ER/LA) opioids about the risk of drug interactions that can lead to serotonin syndrome, as well as effects on the endocrine system, including adrenal insufficiency, and on decreased sex hormone levels.
The updated label won't have specific information on limits regarding dose or duration of use. Though the press release mentioned changes to dosing information -- including initial dosage and changes during therapy -- Sharon Hertz, MD, director of FDA Center for Drug Evaluation and Research's (CDER) anesthesia and analgesic drugs division, told reporters on a conference call that there are no specific recommendations, and this labeling will depend on the product.
The CDC's opioid guidelines, released last week, suggested that physicians carefully assess the risks and benefits of continued therapy when daily doses hit 50 morphine milligram equivalents (MMEs) or more, and they should avoid increasing the dose to 90 MME per day or higher.
"This is a step in the right direction, but I'm disappointed that FDA didn't take the opportunity to add a maximum dose to the label," said Andrew Kolodny, MD, chief medical officer of the rehabilitation organization Phoenix House. "FDA should be supporting CDC's warning against use of doses exceeding 90 mg morphine. It's a shame FDA didn't change the label to reflect the new CDC recommendation."
Hertz added that the agency expects physicians to "use their clinical judgment to determine how to implement the label recommendations."
FDA Commissioner Robert Califf, MD, agreed. "FDA has a role to play [in mitigating the opioid crisis] and we don't want to back off in that role, but we don't regulate medical practice," Califf said on the call. "There are so many different types of pain and different types of patients based on the evidence we have. We have to let medical practitioners do their job."
Califf added that while he acknowledges many physicians don't read labels, it's still an important communication strategy for the FDA, and there are checkpoint measures, such as insurers and electronic health records systems, that rely on label information to enforce physician compliance.
The agency implemented a similar label change to ER/LA opioids in 2013, striking "moderate" pain from the indication, and limiting therapy to those with severe, refractory pain.
When asked why FDA didn't include immediate-release opioids in those changes -- given that these account for 90% of opioid prescriptions in the U.S., compared with only 10% accounted for by ER/LA scripts -- Douglas Throckmorton, MD, deputy director for regulatory programs at CDER, said they focused on the ER/LA products because they could release far higher dosages of opioids if abused.
The new changes affect 87 brands and 141 generics in total; that includes 175 immediate-release products and 34 ER/LA products.
The changes are part of FDA's larger response to the opioid crisis, which included ameeting of its Science Board on opioid policy, and upcoming meetings on opioid indications for pediatric patients.
There will also be a hearing in early May to ascertain whether the current REMS program for ER/LA opioids has been effective. Part of that discussion will include whether or not to extend REMS to immediate-acting opioids, Throckmorton said.
The agency is also focused on development of abuse-deterrent formulations, although during a press briefing last week, CDC Director Thomas Frieden, MD, said while these products may curb the ability to snort or inject these drugs -- an issue that remains under investigation -- they don't address the challenge of stopping oral abuse.
Source : Med Page Today (March 2016)
Overdose on Prescription Opioid Pain Killers
According to a January 2016 CDC report,1 over 47,000 Americans fatally overdosed on prescription opioid pain killers in 2014. This is a stunning fact. But almost as stunning is the apparent lack of concern expressed by the world's media when reporting it. TheNational Council on Alcoholism and Drug Dependence, for example, thought it worth a mere 214 words.2 NBC News was obviously more excited and pushed their coverage to a hefty 223 words.3 And even those who pushed their word totals up slightly higher ignored the real stories hidden behind the headlines.
With that in mind, let's take a look at the CDC report in detail--which virtually no news service did--and then explore the backstory that was pretty much ignored outside of a couple of surprising journalistic players. And finally, I want to take a look a stunning twist to the story that absolutely no one looked at but that to my mind is really the most important takeaway from the whole debacle.
The CDC Report on Increases in Drug and Opioid Overdose DeathsFirst of all, let's make note of the fact that the CDC report is not 200 words long, but 3200 words long. In movie-speak, that means that when the media reported on the story, they left most of it on the cutting room floor. So, what got dumped? As it turns out: the details. And as they say, the Devil is in the details. In broad terms, according to the report, the rate for drug overdose deaths has increased approximately 140% since 2000, driven largely by opioid overdose deaths.
This epidemic isn't being driven by illicit drugs, but by a surge in the use of prescription opioid painkillers.
According to government statistics, nearly 1.9 million Americans now abuse or are dependent onlegal opioids. On the slightly positive side, after increasing steadily every year since the 1990s, deaths involving the most commonly prescribed opioid pain relievers declined slightly in 2012 and remained steady in 2013, showing some signs of progress. Unfortunately, that pause was brief as drug overdose deaths jumped significantly in the last year of the study--from 2013 to 2014. In fact, in 2014, 19,000 people fatally overdosed on prescription painkillers, which represents a 16 percent increase over 2013. Increases in opioid overdose deaths were the main factor in the increase in drug overdose deaths. The death rate from the most commonly prescribed opioid pain relievers (natural and semisynthetic opioids) increased 9%. Concomitantly, the death rate from heroin increased 26%, and the death rate from synthetic opioids, a category that includes illicitly manufactured fentanyl and synthetic opioid pain relievers other than methadone, increased 80%. Nearly every aspect of the opioid overdose death epidemic worsened in 2014. And then there's heroin. In fact, heroin overdose deaths have been sharply increasing since 2010. Surprisingly, as we will discuss later, heroin overdose deaths may not mean quite what you think they mean.
Now, as bad as those broad statistics are, the details behind this epidemic of drug overdose deaths are even worse. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving both opioid pain relievers and heroin. During 2014, a total of 47,055 drug overdose deaths occurred in the United States. From 2013 to 2014, the largest increase in the rate of drug overdose deaths involved synthetic opioids, other than methadone (i.e., fentanyl and tramadol), which nearly doubled from 1.0 per 100,000 to 1.8 per 100,000. Meanwhile, as already stated, heroin overdose death rates increased by 26% from 2013 to 2014 and have more than tripled since 2010, from 1.0 per 100,000 in 2010 to 3.4 per 100,000 in 2014.
As the CDC report explained, from 2000 to 2014, nearly half a million persons in the United States died from drug overdoses. But it gets worse. The killer statistic is that more people died from drug overdoses in the United States in 2014 than during any previous year on record. In 2014, there were approximately one and a half times more drug overdose deaths in the United States than deaths from motor vehicle crashes or gun violence.4 Let that sink in for a moment. Again, we're talking about prescription pain relievers and heroin as the main drugs associated with these overdose deaths, and, surprise, those heroin deaths are likely connected to prescription pain relievers, not to junkies on the street. In summary, the 2014 data demonstrates that the United States' opioid overdose epidemic includes two distinct but interrelated trends: a 15-year increase in overdose deaths involving prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.
But what does that mean?
Drug overdose deaths involving heroin have continued to climb sharply, with heroin overdoses more than tripling in 4 years. This increase mirrors large increases in heroin use across the country and has been shown to be closely tied to opioid pain reliever misuse and dependence. Past misuse of prescription opioids is the strongest risk factor for heroin initiation and use, specifically among persons who report past-year dependence or abuse.5 As it turns out, the increased availability of heroin, combined with its relatively low price and high purity (compared with diverted prescription opioids) appear to be major drivers of the upward trend in heroin use and overdose.6 Finally, illicit fentanyl is often combined with heroin or sold as heroin. Illicit fentanyl might be contributing to recent increases in drug overdose deaths involving heroin. Therefore, increases in illicit fentanyl-associated deaths might represent an emerging and troubling feature of the rise in illicit opioid overdoses that has been driven by heroin.
Bottom line: we're not talking about your typical junkies now, but average people (your friends, neighbors, and co-workers) migrating from prescription pain killers prescribed by their doctors to addiction and then to heroin--and dying as a result.
The Backstory Available to Anyone Who LookedIn the old days, when reporters actually worked stories and practiced journalism, they would have run with the CDC report (heck, they would have actually looked at the CDC report itself rather than merely copying the AP summary of that report) and dug into the story behind it--perhaps even turning it into a series of reports exposing the underbelly of what has grown to become one of the leading causes of death in the United States. But that's when reporters were paid to actually ask questions.
Today, not so much.
In fact, very few media outlets made any attempt to go the extra mile. Two that did were Business Insider7 and The Week magazine, whose staff, in their February 19th issue, pushed beyond the preliminaries to report that it was medical doctors who had fueled this crisis of addiction and deadly overdoses by freely doling out prescription painkillers over the years.8
As stated in their article, "Addiction experts say doctors have fueled this crisis by recommending that patients with even minor ailments and aches take highly addictive opioids like Vicodin, Percocet, and OxyContin. Physicians wrote 259 million opioid prescriptions in 2012, triple the number two decades ago and enough to provide every adult in the country with a bottle of these pills." They then went into the history behind prescription painkillers. I've expanded upon it.
For centuries--before pharmaceutical drugs--people relied on natural pain killers like opium. In fact, laudanum, which is a tincture made from opium, was used as a painkiller as far back as the 1500s until it fell out of favor because of its addictive nature. It was replaced by morphine, an opium isolate that Merck began marketing in 1827. Unfortunately, morphine is even more addictive than laudanum, which caused it too to fall out of favor. Amazingly, morphine was replaced by heroin, which was marketed by Bayer as a non-addictive opioid alternative--despite the fact that it is synthesized from morphine and is two to four times stronger than morphine. Nevertheless, doctors believed the marketing hype and prescribed heroin extensively from the late 1800s to the early 1900s. Obviously, it soon became abundantly clear that heroin was anything but non-addictive. This provided yet another opening for the pharmaceutical companies, which they grabbed onto with a vengeance.
In 1917, three years before heroin was banned in the US, oxycodone was developed by two German scientists. Oxycodone is a semisynthetic opioid synthesized from an alkaloid found in the Persian poppy. In 1939, it was introduced to the US, but it was not until 1950 when it was combined with aspirin and sold as Percodan that it really took off as American physicians began to prescribe it by the truckload. By 1963, the state of California had determined that one-third of all drug addiction in the state was the result of Percodan abuse. Nevertheless, it still took another seven years before the DEA classified it as a Schedule II drug with a high potential for abuse.
Moving on, Percocet and its close cousin Vicodin became the next prescription opioids of choice. Theoretically, they were only to be used for managing pain during terminal illnesses such as cancer, or for acute short-term pain, like recovery from surgery--to ensure patients wouldn't get addicted. But, as The Week explained, in the 1990s, doctors came under increasing pressure to use opioids--particularly Purdue Pharma's new drug OxyContin--to treat the millions of Americans suffering from chronic nonmalignant conditions, like back pain and osteoarthritis. Sensing a marketing opportunity, the National Pharmaceutical Council released a report that actually reframed pain as the "fifth vital sign" that doctors needed to monitor…and treat. In response, numerous "pill mills" began to pop up all over the country. Pill mills are shady doctor's offices, clinics, or health care facilities that routinely conspire in the over-prescribing and dispensing of controlled substances outside the scope of the prevailing standards. In other words, they don't ask too many questions. The bottom line is that the increased availability and acceptability of opioid drugs led to an explosion in prescriptions. Dr. Russell Portenoy, an influential New York--based pain specialist, helped lead the campaign. He claimed prescription opioids were a "gift from nature," and assured his fellow doctors--based on his own 1986 study of just 38 patients--that fewer than 1 percent of long-term users became addicted.9
Purdue Pharma made similar claims for its own drug, OxyContin, and promoted it like diet cola. As The Week reported:
"In fact, when OxyContin went on sale in 1996, Purdue launched a "promotional campaign unlike [anything] we have ever really seen," says opioid abuse expert Dr. Andrew Kolodny. The company gave doctors 34,000 coupons for free OxyContin prescriptions, bombarded them with branded stuffed toys and coffee mugs, and aggressively promoted the idea that the new drug, which is stronger than morphine, was both safe and highly effective. "Drug reps were going to family-care doctors and insisting that OxyContin had no real risks -- only benefits," says Kolodny. Purdue pleaded guilty in 2007 to criminal charges that it misled regulators, doctors, and patients about OxyContin's addictive qualities. But by that point, hundreds of thousands of Americans were hooked."
By 2011, according to an IMS Health National Prescription Audit, 219 million opioid prescriptions were being handed out each year.10 At that point, the prescription painkiller crisis could no longer be ignored, and federal, state, and local law enforcement began to crack down on both drug abusers and doctors who over-prescribe and pressed for the establishment of prescription drug monitoring programs that make it more difficult for drug abusers to get prescriptions from more than one doctor. The number of states with prescription drug monitoring programs has more than doubled, from 20 states in 2006 to 48 states now. Unfortunately, no good deed goes unpunished.....
Source : LaLeva.org
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How Doctors Helped Drive the Addiction Crisis
THERE has been an alarming and steady increase in the mortality rate of middle-aged white Americans since 1999, according to a study published last week. This increase — half a percent annually — contrasts starkly with decreasing death rates in all other age and ethnic groups and with middle-aged people in other developed countries.
So what is killing middle-aged white Americans? Much of the excess death is attributable to suicide and drug and alcohol poisonings. Opioid painkillers like OxyContin prescribed by physicians contribute significantly to these drug overdoses.
Thus, it seems that an opioid overdose epidemic is at the heart of this rise in white middle-age mortality. The rate of death from prescription opioids in the United States increased more than fourfold between 1999 and 2010, dwarfing the combined mortality from heroin and cocaine. In 2013 alone, opioids were involved in 37 percent of all fatal drug overdoses.
Driving this opioid epidemic, in large part, is a disturbing change in the attitude within the medical profession about the use of these drugs to treat pain. Traditionally, opioid analgesics were largely used to treat pain stemming from terminal diseases like cancer, or for short-term uses, such as recovering from surgery.
But starting in the 1990s, there has been a vast expansion in the long-term use of opioid painkillers to treat chronic nonmalignant medical conditions, like low-back pain, sciatica and various musculoskeletal problems. To no small degree, this change in clinical practice was encouraged through aggressive marketing by drug companies that made new and powerful opioids, like OxyContin, an extended-release form of oxycodone that was approved for use in 1995.
The pitch to doctors seemed sensible and seductive: Be proactive with pain and treat it aggressively. After all, doctors have frequently been accused of being insensitive to pain or undertreating it. Here was the corrective, and who in their right mind would argue that physicians shouldn’t try to relieve pain whenever possible?
Well, doctors clearly got the message: The medical use of these drugs grew tenfold in just 20 years. Nearly half of all prescriptions by pain specialists are for opioids. But strikingly, primary care physicians, who generally do not have any particular expertise or training in pain management, prescribed far more opioids overall than pain specialists. For example, in 2012, 18 percent of all prescriptions for opioid analgesics were written by family practitioners, and 15 percent by internists, compared to 5 percent for pain specialists. (This partly reflects the fact that there are fewer pain specialists than primary care doctors.)
The consequences of this epidemic have been staggering. Opioids are reported in 39 percent of all emergency room visits for nonmedical drug use. They are highly addictive and can produce significant depressive and anxiety states. And the annual direct health care costs of opioid users has been estimated to be more than eight times that of nonusers.
But most surprising — and disturbing — of all is that there is actually very weak evidence that opioids are safe or effective for the long-term treatment of nonmalignant pain. So how did they become so popular for these uses? A large review article conducted between 1983 and 2012 found that only 25 of these were randomized controlled trials and only one study lasted three months or longer. The review concluded that there was little good evidence to support the safety or efficacy of long-term opioid therapy for nonmalignant pain. (In contrast, there is little question that opioid analgesics are highly effective for the relief of short-term pain.)
Furthermore, a large 2006 Danish study of a nationally representative sample of 10,066 people that compared opioid and nonopioid users found that opioid use was significantly associated with the reporting of severe pain, poor health, unemployment, and greater use of the health care system. It appears that long-term opioid use did not significantly relieve pain or improve quality of life in this well-designed study.Worse, there is a well-known syndrome of opioid-induced hyperalgesia in which opioids, paradoxically, can actually increase a person’s sensitivity to painful stimuli.
What the public — and physicians — should know is that there is strong evidence that nonsteroidal anti-inflammatory drugs (Nsaids), like Motrin, and other analgesics like Tylenol are actually safer and more effective for many painful conditions than opioid painkillers.
For example, one study found that a combination of Motrin and Tylenol had a much lower so-called number needed to treat than opioids. (The number needed to treat represents the number of people who must be treated for one person to benefit.) A lower number indicates a more effective treatment.
So how should we deal with the national crisis of opioid misuse, addiction and overdose? The Food and Drug Administration has already taken some tiny, though inadequate, steps forward in recent years by issuing a Risk Evaluation and Mitigation Strategy in 2012 that requires the makers of opioids to provide doctors with training and education about using them safely, and adding warnings to drug labels.
WHAT is really needed is a sea change within the medical profession itself. We should be educating and training our medical students and residents about the risks and limited benefits of opioids in treating pain. All medical professional organizations should back mandated education about safe opioid treatment as a prerequisite for licensure and prescribing. At present, the American Academy of Family Physicians opposes such a measure because it could limit patient access to pain treatment with opioids, which I think is misguided. Don’t we want family doctors, who are significant prescribers of opioids, to learn about their limitations and dangers?
It is physicians who, in large part, unleashed the current opioid epidemic with their promiscuous use of these drugs; we have a large responsibility to end it.
Richard A. Friedman is a professor of clinical psychiatry and the director of the psychopharmacology clinic at the Weill Cornell Medical College, and a contributing opinion writer.
Source : NY Times (Nov 2015)
FDA Panel Votes for Tighter Controls on Vicodin
An FDA advisory committee voted 19 to 10 on Friday in favor of moving hydrocodone combination drugs such as Vicodin, Lortab, and Norco into the more restrictive schedule II category of controlled substances.The majority of panelists involved in the 2-day hearing believe the evidence suggests that the drugs are pharmacologically similar to and as susceptible to abuse as other opioids, such as oxycodone combination drugs like Percocet, that fall into the more tightly regulated class.
"We've seen the terribly serious consequences of poor prescribing practices stemming from obvious misclassification of hydrocodone combinations," said panelist Mary Ellen Olbrisch, PhD, professor of psychiatry at Virginia Commonwealth University.
"I don't think the reclassification is a panacea for the opiate abuse problem in the U.S.," she added, "but I think it's an important step in getting physicians to rethink prescribing practices and look at other approaches to pain management."
Moving the drugs from schedule III to schedule II would eliminate a clinician's ability to prescribe up to a 6-month supply of the drugs as well as the ability to simply call in a prescription. For schedule II drugs, doctors can write for no more than a 3-month supply, and a written prescription is mandatory.
The decision has been a long time coming -- beginning with a 1999 citizen's petition that ultimately prompted an inter-agency war between the DEA and the FDA.
This week's 2-day hearing was a compromise that resulted from removal of a hydrocodone reclassification provision from last year's PDUFA reauthorization bill. The hearing was originally scheduled for October but was cancelled because of Hurricane Sandy and its attendant damage across the MidAtlantic states.
At the meeting hearing, industry and advocacy organizations -- including pharmacists and pain specialists -- expressed concerns that reducing access to hydrocodone combination products would limit treatment for patients who in pain.
Their message was countered by addiction specialists and bereaved families who had lost children to prescription painkillers.
Looking at the Numbers
Currently, hydrocodone products are the most widely prescribed agents in the U.S., accounting for 131 million prescriptions for 47 million patients in 2011.
To get a handle on their potential for abuse, FDA and Drug Enforcement Administration (DEA) epidemiologists calculated "abuse ratios" that tried to assess whether this volume of prescribed drugs was tied to more severe outcomes, by comparing it with data for oxycodone combination products.
Numerators included ED visits or poisonings, but depending on the denominator used -- the U.S. population, the number of tablets dispensed, or the overall weight of drugs used -- hydrocodone products appeared both more and less abusable than oxycodone products.
Joseph Rannazzisi, deputy assistant administrator of the office of diversion control at the DEA -- which used total weight when calculating its abuse ratio and concluded that hydrocodone was more widely abused than oxycodone products -- spoke out passionately against statistics.
"I'm not going to talk about denominators. I'm not a statistician or a PhD. I'm just a cop," he said. "Every day I deal in reality, and I know these abusers are taking 10, 20, 30, or 40 tablets" of hydrocodone drugs.
"This drug has got a hold of this society and it's just killing us," he said.
Sharon Walsh, PhD, of the Center on Drug and Alcohol Research at the University of Kentucky, who discussed her work looking at how addictive the agents could be, was asked by a panelist for her interpretation of the research.
"I think they're the same, that's the bottom line from a pharmacological perspective," Walsh said about hydrocodone and oxycodone. "One might wonder why the oxycodone products aren't in schedule III."
Several panelists asked whether a schedule change would have any impact on curbing addiction rates given the fact that oxycodone products are in a more tightly regulated class and are still subject to such wide abuse.
But Rannazzisi said hydrocodone often acts as a gateway drug that gets people started on other opioids.
During the open public hearing portion of the meeting, Sen. Joe Manchin (D-W.Va.) who pushed the amendment to reclassify hydrocodone combos in last year's PDUFA reauthorization bill, and groups representing families who'd lost loved ones to addiction, including Save the Michaels of the World led by Avi Israel, addressed the panel.
Balancing Act: Pain Control vs. Abuse
Representatives from the American Cancer Society, the American Academy of Pain Management, National Association of Chain Drug Stores (NACDS), the Healthcare Distribution Management Association (HDMA), and other groups aired their concerns about patient access and challenges to distribution if the drugs were up-scheduled.
Groups such as the American Academy of Pain Medicine, the American Pharmacists Association (APhA), the American Dental Association, and the American Optometric Association, had time in the regular schedule of the meeting to air their concerns about access.
"This is a balancing act," said Lynne Webster, MD, who represented AAPM. "It's a tradeoff between access for people who derive a benefit from hydrocodone and non-medical use that has caused a great deal of harm."
Some panelists asked if there was a third choice, an alternative solution that would provide more benefit than changing the drug's scheduling. They questioned whether greater use of e-prescribing and Prescription Drug Monitoring Programs, as well as better education efforts for both clinicians and patients, would suffice.
Ultimately, the majority decided that a reclassification into schedule II would be appropriate -- but it remains to be seen how the FDA will interpret their conclusions.
Douglas Throckmorton, MD, deputy director of the FDA's Center for Drug Evaluation and Research, said the issues the panel faced "were among the most challenging I've ever worked on" in the 16 years he's been at the agency.
"It's unquestionable, this epidemic of abuse and death [from opioid narcotics], it's something we need to address as a society," he said. "There's also a need for appropriate access to opioids for patients in pain. Finding a balance between those needs is what FDA will be working on."
Source : MedPage Today
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The Champion of Painkillers
The news about narcotic painkillers is increasingly dire: Overdoses now kill nearly 15,000 people a year -- more than heroin and cocaine combined. In some states, the painkiller death toll exceeds that of car crashes.
The head of the Centers for Disease Control and Prevention has declared the overdoses from opioid drugs like OxyContin an "epidemic." And a growing group of experts doubts that they work for long-term pain.
But the pills continue to have an influential champion in the American Pain Foundation, which describes itself as the nation's largest advocacy group for pain patients. Its message: The risk of addiction is overblown, and the drugs are underused.
What the nonprofit doesn't highlight is the money behind that message.
The foundation collected nearly 90 percent of its $5 million funding last year from the drug and medical-device industry -- and closely mirrors its positions, an examination by ProPublica found.
Although the foundation maintains it is sticking up for the needs of millions of suffering patients, records and interviews show that it favors those who want to preserve access to the drugs over those who worry about their risks.
Some of the foundation's board members have extensive financial ties to drugmakers, ProPublica found, and the group has lobbied against federal and state proposals to limit opioid use. Painkiller sales have increased fourfold since 1999, but the foundation argues that pain remains widely undertreated.
The group says industry money has had no effect on its advocacy.
"I'm convinced with every shred of my body that our interest is improving the lives of people affected by pain," said Will Rowe, the foundation's chief executive, "and we want to do that the best way we can."
The problem isn't opioids, Rowe and other group leaders say. It's poorly trained doctors who prescribe them too easily or in excess.
Yet, critics say the Baltimore-based foundation is making it harder to address a major public-health problem.
"If you were a drug company, wouldn't it be smart to make it look like you had a patient-oriented group?" said Dr. Gary Franklin, a Washington state official who tussled with the foundation over new restrictions on high-dose painkillers.
Its funding makes the group "one and the same" with the pain industry, Franklin said.
In stories this year, ProPublica has detailed the close entanglements between pharmaceutical companies and groups representing doctors. Reporting showed that the positions of societies representing specialty physicians often reflected the views of their major funders.
The American Pain Foundation falls into a different category -- health advocacy. It harnesses the power of patient stories to sway politicians, state medical boards, judges and government health regulators, emphasizing that it represents grassroots voices.
ProPublica's review found that the foundation's guides for patients, journalists and policymakers play down the risks associated with opioids and exaggerate their benefits. Some of the foundation's materials on the drugs include statements that are misleading or based on scant or disputed research.
The group has intervened in court cases in ways that appear to counter its stated mission. In one example, it sided with Purdue Pharma, its longtime funder, to block a 2001 class-action case filed by Ohio patients who had become addicted to or dependent on the company's blockbuster painkiller, OxyContin.
And the foundation mobilizes patients to send "outraged" email messages to news organizations that run stories it believes reinforce "stigmas and stereotypes" about the risks of pain medication.
The group's board includes some patients but also doctors who are paid to speak and consult for drug companies, a researcher whose clinic has relied on their funding for survival and a public-relations executive whose firm represents them.
Last year, one board member was the lead author of a study about a Cephalon drug. Cephalon sponsored the study, and its employees were co-authors. The study found that the drug, Fentora, was "generally safe and well-tolerated" in non-cancer patients even though it is only approved for severe cancer pain.
Dr. Andrew Kolodny, a New York psychiatrist who heads Physicians for Responsible Opioid Prescribing, said the foundation has built credibility with politicians and regulators who may not be aware of the extensive industry ties.
"I don't think they realize that in many ways the American Pain Foundation is a front for opioid manufacturers," Kolodny said.
Rowe, however, said it can be hard for critics to understand the mindset of patients whose pain is so severe they are willing to risk serious side effects to gain relief.
"Policymakers can go to bed at night and say, 'Well, I protected society,'" by restricting access to a risky painkiller," he said. "The person with pain or the person with cancer could say, 'You know, I'm sorry. I'm living with this, and I want to take this chance.'"
'The System Is Awash in Opioids'
In the late 1980s and early '90s, physicians who cared for pain patients excitedly embraced opioids as a low-risk treatment for suffering.
Derived from the opium plant, opioids reduce the perception of pain by attaching to opioid receptors in the brain, spinal cord and elsewhere in the body.
"We bought into this idea that opioids would be effective and that the risk of addiction would be low," said Dr. Jane Ballantyne, a longtime pain expert and a professor at the University of Washington.
But along the way, pain doctors split. Some, like Ballantyne, began decrying the increasingly widespread use of opioids and questioned whether the drugs worked. Others, like the foundation's leaders, said the drugs were being unfairly maligned, making pain patients feel like criminals and discouraging doctors from prescribing them.
Despite the debate, sales of the drugs have skyrocketed.
Last year, $8.5 billion worth of narcotic painkillers were sold in the United States, according to the prescription-tracking company IMS Health. Enough of the drugs were prescribed last year to "medicate every American adult around the clock for a month," the CDC said.
"Right now, the system is awash in opioids, dangerous drugs that got people hooked and keep them hooked," said CDC Director Thomas Frieden in a recent news briefing.
Some of the pills have become household names: Vicodin, Percocet, OxyContin. On its own, OxyContin, an extended-release painkiller, accounted for $3.1 billion in sales last year, up from $752 million in 2006, according to IMS Health.
There's little dispute that many people endure chronic pain. In the past, many doctors, especially those providing primary care, ignored pain as a condition that warranted its own treatment.
A report from the prestigious Institute of Medicine last summer said 116 million American adults suffer from chronic pain. The report also cited legal and regulatory barriers to opioids, especially for cancer and end-of-life pain. The findings are lauded by the foundation as underscoring the concern about undertreatment.
In an email to ProPublica, however, the report's chairman said the study panel took a broad look at chronic pain and didn't examine the use of opioids with "rigor or detail."
"It does seem like the issue of opioid use is worthy of a separate study," wrote Dr. Philip A. Pizzo, dean of Stanford University's medical school.
Guides Offer Reassurance About Pain Drugs
The American Pain Foundation's website offers publications for patients, policymakers and even journalists. Each depicts the benefits of opioids, and each is underwritten by the makers of those drugs.
Its patient guide, paid for by four companies, discusses several treatments for pain. It says such pain relievers as aspirin, ibuprofen and naproxen commonly cause gastrointestinal bleeding or ulcers, delay blood clotting, decrease kidney function and may increase the risk of stroke or heart attack. And it warns patients to use these pain pills at the lowest dose and stop them unless clearly needed.
The side effects of opioids, on the other hand, are minor, and most go away "after a few days," the foundation's guide says. The underuse of opioids, it says, "has been responsible for much unnecessary suffering."
Patients, it says, shouldn't worry if they need more of a drug. They are not developing an addiction.
"Many times when a person needs a larger dose of a drug," the guide says, "it's because their pain is worse or the problem causing their pain has changed."
Another guide, written for journalists and supported by Alpharma Pharmaceuticals, likewise is reassuring. It notes in at least five places that the risk of opioid addiction is low, and it references a 1996 article in Scientific American, saying fewer than 1 percent of children treated with opioids become addicted.
But the cited article does not include this statistic or deal with addiction in children.
"I would much prefer that they would put in there something that could be substantiated by a real reference," said Dr. Leonard Paulozzi, a CDC medical epidemiologist specializing in drug overdoses. "That would present a much less rosy picture of the risk."
A recent report by the National Institute on Drug Abuse said estimates of addiction among chronic pain patients using opioids range from 3 percent to as high as 40 percent.
One Foundation-related publication this year provided a case study of how physicians could convince patients that the drugs are not addictive.
In an e-newsletter paid for by a drug company, Florida family physician Louis Kuritzky summed up the advice he'd give to a patient with knee pain: "We have learned that when patients have important pain problems like you do, they can use such medications successfully over the long term without any major risk of addiction."
This advice is contradicted by a respected medical review organization that looked at research on the use of opioids for osteoarthritis of the knee or hip. The Cochrane Collaboration concluded that "the small to moderate" benefits of opioids "are outweighed by large increases in the risk of adverse events" and the drugs should not be routinely used.
Kuritzky said he had not read the Cochrane review but believes that the downside of opioids is "very, very small" based on his experience with his patients.
"There are many issues where you will see wise men and women differ about the right answer to a difficult and important question," he said.
Rowe, the foundation's chief executive, acknowledged that some of its publications need updating. He pointed to additional materials on the group's new PainSAFE website, which include a broader description of the risks. But the foundation continues to post outdated guides and even refers to them in newer materials.
And while the PainSAFE site discusses the risks more completely, it is based on the assumption that the drugs have proven to work well for chronic pain sufferers. The site says studies have shown opioids improve daily function and quality of life for such patients. In contrast, a new guide by New York City's Department of Health and Mental Hygiene says there is "insufficient evidence" that "pain relief is sustained or function improves."
Dr. Lewis Nelson, chairman of the federal Food and Drug Administration's Drug Safety and Risk Management Advisory Committee, said he believes the foundation's guides can't help but be biased.
"If you're taking drug-company money and you're working as an advocacy group for patients, I think by definition you're biased," said Nelson, an emergency room physician in New York. "I take everything they say with a grain of salt."
Fighting in Court for Painkiller Access
The foundation doesn't just offer advice about opioids; it takes its arguments into court.
In 2005, it filed a friend-of-the-court brief in the U.S. Fourth Circuit Court of Appeals in support of Dr. William Hurwitz, a pain doctor in Virginia who had been convicted on 50 counts of drug trafficking.
The doctor had been accused of prescribing a single patient as many as 1,600 Roxicodone pain pills in one day. Hurwitz allegedly had prescribed that patient alone more than 500,000 pills between July 1999 and October 2002.
The pain foundation and its allies argued that the jury instructions in the case didn't distinguish between criminal behavior and mistakes by a well-intentioned physician. "It is not drug dealing to prescribe opioids to patients that might be 'suspected' addicts or substance abusers," the foundation and two other groups wrote in a brief.
Rowe said the foundation intervened in the case on principle, fearing the drugs would be "demonized." The appeals court threw out the conviction, but Hurwitz was retried and convicted on 16 counts of trafficking.
Years earlier, the foundation opposed several pain patients who had sued Purdue Pharma in an Ohio county court for allegedly obscuring the risks of OxyContin.
The foundation filed a friend-of-the-court brief backing Purdue, arguing that the health of all pain patients would be harmed if the class-action lawsuit went forward because doctors would become fearful of prescribing opioids.
Ohio was plagued by "opiophobia" according to a brief co-authored by the foundation and two smaller pain nonprofits. "Consequently many, if not most, of the state's residents had been deprived of adequate pain care," it said.
The Ohio Supreme Court decided in 2004 not to allow a class action.
In a separate federal case in 2007, Purdue pleaded guilty to misbranding OxyContin "in an effort to mislead and defraud physicians and consumers," according to a statement from prosecutors. The company agreed to pay $600 million in penalties. Three top officials also pleaded guilty to misdemeanors and agreed to pay $34.5 million.
Two months after the conviction, however, then-foundation chairman Dr. James Campbell praised Purdue in a statement to a U.S. Senate committee.
"I believe Purdue and its management deserve recognition for their contribution to the welfare of these many patients," Campbell wrote. Prosecuting the executives, he wrote, sent a "chilling message to those who dare to develop high-risk drugs for important diseases."
Campbell mentioned his foundation role in his remarks. Rowe said the former board chairman was not speaking for the group, and stressed that strict rules keep funders from influencing its work. The foundation is working to diversify its support, Rowe and others said.
Nevertheless, the group often finds itself on the same side as drugmakers in state and federal debates over how to regulate painkillers.
In 2009, the FDA suggested changes to address concerns about the risks of long-acting opioids, recommending that physicians and pharmacists be certified to ensure they had been educated about those risks.
Although foundation officials blame poorly educated physicians for the growing problems with opioids, the officials joined with other pain groups and drugmakers to assail the plan.
The FDA backed off key elements of its proposal last year and said doctors could voluntarily attend courses about the risks.
That move was criticized by an FDA advisory committee, which voted overwhelmingly that it wasn't enough to stem the tide of overdose deaths.
"When you look at 14,000 people dying on an annual basis, that's more than we've lost in Iraq and Afghanistan since 2001 in active duty," Dr. Mori Krantz, an advisory panel member and director of the prevention center at the University of Colorado in Denver, said during the meeting.
Little Evidence That Narcotics Work for Chronic Pain
Missing from the American Pain Foundation literature is any suggestion that the drugs don't work for many chronic pain sufferers.
Recent editorials in medical journals and scientific reviews cite little evidence of long-term benefit.
Most of the clinical trials for opioids to treat chronic pain "were small, lasted less than 16 weeks and excluded patients with a history of substance abuse, psychiatric illness and depression, who are at increased risk for opioid misuse and abuse," three physicians wrote in an editorial this year in the Archives of Internal Medicine.
"How can a therapy be considered if there's no evidence that it works and there's evidence of lots of side effects?" Dr. Mitchell Katz, one of the authors and director of the Los Angeles County Department of Health Services, said in an interview.
Rowe said he knows plenty of patients for whom the drugs work, "and their lives are together because they use them."
The foundation board's chairman and president, Dr. Scott Fishman, is stepping down at the end of the month. In a statement to ProPublica, he said his views have evolved and that he now believes opioids are both overused and addictive. But he defended the group.
"I have not always agreed with APF positions and have had disagreements with some APF leaders and patient advocates about many issues in pain management, including the appropriate place of chronic opioid therapy," wrote Fishman, chief of pain medicine at University of California, Davis.
"Nonetheless, I have always believed that patients in pain in the United States need strong patient advocacy, which APF has offered."
Source : ProPublica
Link to Source
Prescription Narcotics Cause More Deaths Than Both Heroin and Cocaine
NATURAL NEWS (LINK TO FULL ARTICLE)
On the heels of the sudden death of celebrity actress Brittany Murphy, people are once again raising the question of just how dangerous prescription drugs might really be.
Some are arguing, however, that street drugs are the real danger, not prescription drugs. But the following study demonstrates why prescription drugs are far more dangerous than illegal recreational drugs.
According to a new study conducted by physicians at St. Michael's Hospital and the Institute for Clinical Evaluative Sciences (ICES) in Toronto, the number of deaths due to prescription opioid use has doubled between 1991 and 2004. Following the introduction of oxycodone into Toronto's drug formulary in 2000, there has been a 500% increase in deaths due to the drugs.
Researchers reviewed over 7,000 files from the Office of the Chief Coroner in Ontario and found that between the years of 1991 and 2004, oxycodone prescriptions increased by more than 850 percent, representing about one-third of the opioid prescriptions given in 2006. (This is the largest prescription increase among all opioid drugs.)
Following the addition of this drug into the provincial drug benefit plan in 2000, deaths from opioid usage rose by 41 percent. Shockingly, deaths from prescription opioids like oxycodone were far greater than deaths from heroin. The vast majority of people who died from opioids had visited their doctor and received a prescription for the drug within a month of their death.
The total number of opioid-related deaths in Toronto in 2004 is estimated to be 27.2 per million people. Study authors said they hope to shed light on the tremendous dangers associated with prescription opioid drugs.
Coked up on prescription smack It's the dirty little secret of the pharmaceutical industry: More people are killed by prescription opioids than all those killed by heroin and cocaine combined. And that probably even includes all the shootings of gang bangers in northern Mexico.
Prescription drug abuse is now more common than street drug abuse -- by far! And yet Big Pharma rakes in huge profits from all the patient addictions to their opioids. And by "opioids", what I mean is narcotics. They are, in fact, one and the same.
So of all the drug addicts in America today, you can divide them into two camps:
1) People addicted to street drugs.
2) People addicted to prescription drugs.
The people in group #1 (street drugs) are taken to jail where they are given prison sentences. People in group #2 (prescription drugs) are taken to their doctor where they are given prescription refills. It's all really the same narcotics, it's just that one group is legal and the other is illegal.
And what really determines whether a particular narcotic is legal or illegal? Whether or not Big Pharma profits from it. If Big Pharma makes money off the narcotics, they're considered legal.
Big Pharma, you see, earns tens of billions of dollars each year from drug addicts. And just by coincidence, it turns out that their prescription narcotics are extremely addicting, guaranteeing repeat business. The business model is so dang lucrative, you might think they were drug dealers...
Why do you think the main sponsors for the Partnership For A Drug-Free America are the drug companies themselves? It's because Big Pharma is trying to eliminate the competition. By keeping up the so-called "War on Drugs" front, the pharmaceutical industry can make sure it dominates the market for narcotics. After all, if you're going to feed narcotics to a nation full of junkies, why not make a hefty profit on it? That's the thinking of drug companies, it seems, as they have done basically zilch to effectively stem the abuse of their own prescription narcotics.
Much like the tobacco companies, drug companies secretly want people to be addicted to their products.
Sources for this story include:
NATURAL NEWS (LINK TO FULL ARTICLE)