VA Study Could Lead to More Cuts in Opioid Prescribing

By Pat Anson, Editor

A new study by a prominent think tank could give further ammunition to the Department of Veterans Affairs to reduce access to opioid pain medication in its healthcare system.

Researchers at the RAND Corporation studied data from nearly 32,500 patients who were treated at VA facilities in 2007 and were identified as having an opioid use disorder. The goal was to identify “quality measures” that could help reduce the death rate of addicted patients.

The researchers found that deaths were much lower among patients who were not prescribed opioids or anxiety medications, those who received counseling, and patients who had regular visits with a VA physician. They estimate the number of deaths could be reduced by a third if all three quality measures were adopted. 

"This is a very large drop in mortality and we need to conduct more research to see if these findings hold up in other patient care settings," said Dr. Katherine Watkins, a physician scientist at RAND and lead author of the study published in the journal Drug and Alcohol Dependence.

"But our initial findings suggest that these quality measures could go a long way toward improving patient outcomes among those who suffer from opioid addiction."

The findings suggest that a key to reducing mortality is to minimize the prescribing of opioid medication and benzodiazepines to veterans with opioid addiction. Benzodiazepines are a class of psychiatric medication used to treat anxiety disorders.

Because lower death rates were also associated with counseling and quarterly visits with a VA physician, researchers concluded that addicted patients benefit from making a connection with a caregiver, who can identify changes in their behavior and potential for relapse.

Surprisingly, patients in the study who were prescribed addiction treatment drugs such as Suboxone (buprenorphine) did not have lower death rates.

"We know from other research that medication-assisted therapy can help people stay off drugs, get jobs and lead more-productive lives," Watkins said. "But in this study, the treatment strategy was not associated with lower mortality."

The VA has already taken a number of measures to reduce opioid prescribing, including a new guideline that strongly recommends against prescribing opioids for chronic pain. VA physicians are also being urged not to prescribe opioids long-term to anyone under the age of 30. The guideline recommends exercise and psychological therapies such as cognitive behavioral therapy as treatments for chronic pain, along with non-opioid drugs such as gabapentin.

“We’ve been working on this now for seven years and we’ve seen a 33 percent reduction in use of opioids among veterans, but we have a lot more to do. We have a lot we can learn,” Secretary of Veterans Affairs David Shulkin told a White House opioid commission earlier this month. "At the VA, my top priority is to reduce veteran suicides. And when we look at the overlap with substance abuse and opioid abuse, it’s really clear.”

According to a recent VA study, an average of 20 veterans die each day from suicide, a rate that is 21 percent higher than the civilian population.  Veterans also suffer from high rates of chronic pain, depression and post-traumatic stress disorder.

Acetaminophen May Harm Male Fetuses

By Pat Anson, Editor

The pain reliever acetaminophen may inhibit the sexual development of male babies whose mothers take the over-the-counter drug while pregnant, according to a new study by Danish researchers. The study only involved laboratory rodents, but one researcher called the findings “very worrying” and said pregnant women should think carefully before using the painkiller.

Acetaminophen – which is more commonly known as paracetamol outside the U.S. -- is used by over half the pregnant women in the United States and European Union. It is the active ingredient in Tylenol, Excedrin, and hundreds of pain medications.

Previous research has already indicated that acetaminophen can suppress the development testosterone in male fetuses. It has also been linked to autism and attention deficit problems in young children.

The new study, published in the journal Reproduction, involved mouse fetuses that were exposed to acetaminophen at varying doses. The dose that produced the most effect was three times higher than the maximum recommended daily dose in humans.

Researchers evaluated the male rodents' behavior after their birth, studying their aggressiveness toward other male mice, their ability to mark their territory, and their ability to mate. They were found wanting in all three areas.

The abnormal behavior was apparently caused by lower levels of testosterone, the male sex hormone that fuels the development and programming of the male body and brain. Testosterone also controls sex drive and the production of sperm.

"We have demonstrated that a reduced level of testosterone means that male characteristics do not develop as they should. This also affects sex drive," said Dr. David Møbjerg Kristensen of the Department of Biomedical Sciences at the University of Copenhagen. "Mice exposed to paracetamol at the fetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their fetal development, and this could be seen long afterwards in their adult life. It is very worrying."

When the brains of the mice exposed to acetaminophen were analyzed, researchers found significantly fewer neurons in the brain region that controls sex drive.

“These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP (acetaminophen) by pregnant women,” said Kristensen.

A study published last year in JAMA Pediatrics  linked prenatal use of acetaminophen to a higher risk of behavior problems, hyperactivity and emotional problems in children. The pain reliever has also long been associated with liver injury and allergic reactions such as skin rash.

The FDA label for products containing acetaminophen warns about the risk of liver damage and other side effects, but does not specifically warn pregnant women about using the pain reliever. The agency said in 2015 that the evidence was “too limited” to justify such a warning.  

In its 2016 opioid prescribing guidelines, the CDC recommends acetaminophen as an alternative to opioid pain medication. The guideline only briefly mentions that acetaminophen was involved in nearly 900 overdose deaths in 2010 and can cause liver problems. The guideline does warn pregnant women -- at length -- that opioids can cause birth defects, poor fetal growth, still births and neonatal opioid withdrawal syndrome.

Do Depression and Back Pain Lead to More Opioids?

By Pat Anson, Editor

Depressed patients with low back pain were twice as likely to be prescribed an opioid medication and to receive higher doses, according to the results of a new study that looked at data from a decade ago.

Lower back pain is the world’s leading cause of disability and the most common condition for which opioids are prescribed. Nearly a quarter of the opioid prescriptions written in the U.S. are for low back pain.

"Our findings show that these drugs are more often prescribed to low back pain patients who also have symptoms of depression and there is strong evidence that depressed patients are at greater risk for misuse and overdose of opioids," said John Markman, MD, director of the Department of Neurosurgery's Translational Pain Research Program at the University of Rochester Medical Center and senior author of the study published in the journal PAIN Reports.

The researchers found that patients who screened positive for depression were more than twice as likely to be prescribed an opioid, and they received twice the cumulative dose of opioids per year.

This not only suggests that doctors were more likely to prescribe opioids to a patient suffering both physically and psychologically, but it also implies that analgesics are less effective in pain patients who are depressed.

One obvious weakness of the study is that it relied on prescription data from 2004 to 2009 that was compiled by the Medical Expenditure Panel Survey, a federal survey of patients, their families, healthcare providers and employers. That time frame coincides with a steep rise in opioidprescribing, but does not represent the current environment in which opioid medication is harder to obtain.

The researchers believe, however, that understanding prescribing patterns from a decade ago may help improve the effectiveness of clinical trials. Low back pain is the condition most often studied to approve new pain medications, and depressed patients are often excluded from trials because of incentives to get positive findings about a new analgesic.

“Because several pivotal clinical trials for opioid treatment of LBP (low back pain) have systematically excluded the most depressed patients, it is probable that clinicians and patients alike are drawing conclusions from a study group that may differ in important ways from likely opioid recipients. These clinical trial populations may underrepresent the patients most likely to receive opioids, especially those who are mostly likely to receive higher dosages for longer durations,” Markman said.

Lower back pain may be the world’s leading cause of disability, but there is surprisingly little evidence about the best ways to treat it.

A recent review of 20 clinical studies involving nearly 7,300 patients found that opioids provide only “modest” short-term relief from lower back pain. Opioids were also no more effective than non-steroidal anti-inflammatory drugs (NSAIDs). About half of the patients involved in the studies dropped out because they didn’t like the side-effects of opioids or because they found them to be ineffective.

CDC Guidelines Making Opioid Problem Worse

By Gary Nations, Guest Columnist

I’m a medically retired police officer with over 22 years of service. I have been in chronic pain management for many years now and my condition will never get better.

Throughout my time dealing with workers compensation and the public employee retirement system in Mississippi, I have been examined by no less than five medical doctors. Unfortunately for me, the conclusion is my condition is progressive and will only get worse.

I’ve had four neck surgeries and one lower back surgery due to on-the-job injuries. For the past few years I have found a pain management regimen that allows me to have somewhat of a normal life, although I still experience pain 24/7. I would love to see a substance that relieved pain without the problems caused by opioid medication.

The recent upswing in deaths from opioid abuse is tragic. However, the guidelines developed by the CDC for doctors to reduce opioid dosages for pain patients like me will cause more problems than it solves.

I believe some of the actions taken so far have created a vacuum and worsened the epidemic, which I believe is about to get much bigger.  Some people are going to abuse some type of substance no matter what. That’s an unfortunate fact that cannot be stopped.

Cutting the dose of medication for people in my position who need it will force them to violate the law to maintain their level of pain management and quality of life.

GARY NATIONS

This could prove a disaster, as we know many street drugs contain powerful opioids such as fentanyl, which the DEA has been very unsuccessful in stopping. Some of these street drugs are counterfeit. They appear to be a medication that a doctor would prescribe, yet they contain other drugs that cause people to overdose and die. From what I read and understand, this is what happened to the entertainer Prince. Some patients may also tire of the constant pain and commit suicide with street drugs.

The Declaration of Independence endows each citizen the right to life, liberty and the pursuit of happiness. I believe the CDC’s attempt to curb the opioid overdose and death rate is very noble. However, I also believe in the long run it will violate citizens’ rights, do much more harm than good and end up in the civil courts. As I’m sure you are aware, in some cases large sums of money are paid out each year in legal cases for “pain and suffering.”

There is no way the CDC can tell what medication and how much medication I or anyone else needs to attempt to maintain their current level of activity, quality of life and pursuit of happiness.  Only a qualified physician with medical training, medical records and medical images can understand what a patient may or may not need. The CDC needs to remember there are many people with very legitimate needs for these controlled substances. 

Last year was the first time in over ten years I could enjoy hunting and fishing again. I became active enough that I went from 255 pounds down to 215 pounds. I started feeling better and asked my doctor to drop my “breakthrough” pain meds from 120 to 90 per month. I’ve since realized I really need about 100 per month, but I get by.

The key here is I volunteered to stop taking 30 pills per month. Yes, my doctor was surprised.  However, because of rule changes, I can’t get my pain meds from that doctor anymore. I have to drive one hour each way to a pain management doctor to get my meds now. The long drive is very painful and the cost is higher.

Cutting my current pain management regimen will result in me being in more pain than I am now. It will cause me to be unable to exercise my right to hunt and fish. It will cause me to be unable to do yard work, such as mowing the lawn. Not being able to mow the lawn will result in an additional expense of $80 to $100 per month during the warm weather months.

It will cause me to once again be unable to travel and engage in some aspects of the only hobby I can currently enjoy, amateur radio. In other words, much of my liberty will be taken and my quality of life heavily impacted. My only income is Mississippi Public Employees Retirement System disability payments. Some citizens that are currently able to work with proper pain management may also have to seek disability if their doses are cut.

As I stated, I believe the effort to stop drug abuse and addiction is very noble. However, the route to solving this opioid problem should not include violating the rights of our disabled citizens or cause some patients to become criminals while trying to maintain what little normalcy and quality of life they have now.

I’m seeking your help to stop the CDC from punishing citizens that need to be on long term pain management and to get the CDC to reevaluate how it is handling a very important problem. I believe it’s time for someone to help us by filing for an injunction or a class action lawsuit to stop this craziness.

Gary Nations lives in Mississippi.

Pain News Network invites other readers to share their stories with us.  Send them to:  editor@PainNewsNetwork.org. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Addiction Treatment Initial Focus of Opioid Commission

By Pat Anson, Editor

President Trump’s commission on drug addiction and the opioid crisis held its first public meeting today, a two-hour session focused largely on expanding access to addiction treatment.

Chaired by New Jersey Governor Chris Christie, the commission is expected to make interim recommendations to the president in the next few weeks on how to combat drug abuse, addiction and the overdose epidemic, which is blamed for the deaths of nearly 60,000 Americans last year. A final report from the commission is due by October 1.

It is not clear yet how much of a role opioid prescribing and pain medication will play in the commission’s work. Most of its five members have publicly blamed overprescribing for causing the opioid epidemic.

“No offense, but that is where this came from,” said Massachusetts Gov. Charlie Baker, a commission member.

“The opioid crisis is ruining lots of people’s lives and lots of families across America," David Shulkin, Secretary of Veterans Affairs told the commission. "At the VA, my top priority is to reduce veteran suicides. And when we look at the overlap between substance abuse and opioid abuse, it’s really clear.

“We’ve been working on this for seven years and we’ve seen a 33 percent reduction in use of opioids among veterans, but we have a lot more to do.”

Shulkin did not mention that veteran suicides have soared during that period, and are now estimated at 20 veterans each day.

“We also need to look at pharmaceutical companies making generic drugs more tamper resistant and looking at making drugs that do not cause addiction,” said North Carolina Gov. Roy Cooper, a commission member.

Commission member Patrick Kennedy, a former congressman who has battled substance abuse himself, said there has been a “historic discrimination” against mental health and addiction treatment.

“I’m excited by the chance to kind of push for ways that we can hold insurance companies more accountable, so that the public sector doesn’t have to pick up the tab. Because its taxpayers that are picking up the tab when insurance companies continue to push folks with these illnesses off into the public system,” Kennedy said. “This is a cost shift that is a windfall for insurance companies if they can get rid of people who have mental health or addiction issues.”

Limits on Opioid Medication Not Working

“Let me be blunt. Today there is not nearly enough drug treatment capacity in America to help most of the victims of the epidemic,” said Mitchell Rosenthal, MD, who founded Phoenix House, a nationwide chain of addiction treatment centers.

“Most terrifying is the reality that nothing we are doing today has been able to halt the spread of opioid addiction. Controlling prescription opioid medication has not done so. Prescription monitoring programs, strict limits on the number of pills physicians can prescribe, and the CDC pain management guidelines seem to have capped usage of prescribed opioid medications. But overdose deaths from heroin and highly potent synthetics like fentanyl have gone through the roof.”

One activist called for wider adoption of the CDC opioid guidelines and rigid enforcement if doctors don’t follow them. Gary Mendell, the CEO and founder of Shatterproof, a non-profit focused on preventing addiction, said each state should be held accountable and federal funding reduced to states if their prescribing exceeds a certain level.

“If every primary care doctor in this country followed the CDC guideline, you would cut by more than half, instantly, the number of new people becoming addicted,” said Mendell, whose son committed suicide after years of struggle with addiction. “We need a goal for the country. Divide it up by 50 states, a proper goal developed by the CDC, and then we need to publicize it and hold people accountable. Just like you would do in any business.”

Patrick Kennedy is a member of Shatterproof's board of advisors, and Andrew Kolodny, MD, founder and Executive Director of Physicians for Responsible Opioid Prescribing (PROP) is a member of its "opioid overdose advisory board."

No pain patients or pain management experts testified before the commission or were appointed to the panel.

Watch below for a replay of today's meeting:

Will New Laws Punish Pain Patients?

By Pat Anson, Editor

Recent efforts by state and federal lawmakers aimed at punishing drug traffickers could wind up sending people to prison simply for seeking pain relief, according to critics.

This week the American Kratom Association (AKA) sent an action alert to members warning that a bill introduced by Sen. Chuck Grassley and Sen. Dianne Feinstein could be a “backdoor way” of banning kratom -- an herbal supplement that millions of people use as an alternative to opioid painkillers.

The “Stop the Importation and Trafficking of Synthetic Analogues Act of 2017” – also known as the SITSA Act – would give the Attorney General the power to list as a “Schedule A” substance any unregulated drug that has a chemical structure similar to that of a drug already listed as a controlled substance. A similar measure has been introduced in the House.

The bills are ostensibly aimed at banning chemical cousins or “analogues” of fentanyl, a powerful synthetic opioid blamed for thousands of overdose deaths that is increasingly appearing on the black market.

But kratom supporters fear the SITSA Act could also be used to ban kratom, something the Drug Enforcement Administration tried unsuccessfully to do last year, claiming it was an "opioid substance" with “a high potential for abuse.” Kratom is not an opioid, but it has opioid-like properties that reduce pain or act as a stimulant or depressant – much like a controlled substance.

“So now the anti-kratom bureaucrats in Washington want to ban kratom simply by claiming it has the same effects as an opioid – calling it an ‘analogue’ of the opioid,” said Susan Ash, the AKA’s founder and spokesperson. “After everything that we’ve fought successfully against and endured together as a movement, our lobbyists are concerned that this is now the perfect storm for banning kratom.”

Ash wants the SITSA Act to be amended to exclude natural botanicals like kratom. In its current form, she says the bill could impose prison sentences of up to 20 years for importers or exporters of kratom, which is made from the leaves of a tree that grows in southeast Asia.

Florida Law Stiffens Penalties for Fentanyl

A new law in Florida is also intended to crackdown on fentanyl dealers, but critics say it could wind up sending unsuspecting pain patients to prison as well.

Signed into law yesterday by Gov. Rick Scott, it requires mandatory minimum sentences for defendants convicted of selling, purchasing or possessing illicit fentanyl.

Anyone caught with as little as four grams of fentanyl would face a minimum of three years in prison. Sentences escalate depending on the amount of fentanyl seized and murder charges could be filed if someone dies of a fentanyl overdose.

Dealers often mix fentanyl with heroin or sell it in counterfeit pills disguised to look like oxycodone or other prescription painkillers. Many users have no idea they’re buying fentanyl, which is 50 to 100 times more potent than morphine.

"There's a massive problem with counterfeit pills," Greg Newburn, state policy director for Families Against Mandatory Minimums told the Miami New Times. "You have people who think they’re buying oxy pills who will end up getting labeled as traffickers in fentanyl.”

DEA PHOTO

Florida has been down this path before. According to an investigative series by Reason.com, mandatory minimum sentences in Florida for oxycodone and hydrocodone trafficking resulted in 2,300 people being sent to prison, most of them low-level drug users or patients who went to the black market seeking pain relief. 

“The signing of this bill by Gov. Scott is another example of using get tough drug policies for political gain,” said Tony Papa, Manager of Media and Artist Relations for the Drug Policy Alliance. “This is not going to stop the sale of heroin in Florida. It's another prosecutorial tool that will be used for bargaining by district attorneys in drug cases.  Under this new law many individuals will be subject to the death penalty for a 10 dollar bag of dope. It's totally insane!”

Wisconsin to Involuntarily Commit “Drug Dependents”

A bill that recently sailed through the Wisconsin legislature with little opposition would allow for the involuntary commitment of someone who is drug dependent. The bill’s sponsor, Assemblyman John Nygren, has a daughter who has struggled with heroin addiction and served time in jail.

Current Wisconsin law allows for the involuntary commitment of alcoholics if three adults sign a petition alleging that a person lacks self-control over their use of alcohol and whose health is substantially impaired. 

The new bill adds “drug dependence” to the list of reasons someone can by committed. Dependence is defined as a person’s use of one or more drugs that is beyond their ability to control and that substantially impairs their health or social functioning.

The bill is one of nearly a dozen anti-opioid measures sponsored by Nygren that Gov. Scott Walker asked to be approved in a special legislative session. It now heads to his office for consideration.

Aspirin Risky for Seniors 75 and Older

By Pat Anson, Editor

The old cliché about a doctor telling you to “take two aspirin and call me in the morning” isn’t such great advice after all. Especially for seniors aged 75 and older.

A daily dose of aspirin has long been recommended as a way to prevent a heart attack or stroke. But British researchers at the University of Oxford say the blood thinning effects of aspirin substantially raise the risk of gastrointestinal bleeding as patients grow older.

Their study, published in The Lancet medical journal, estimates that aspirin causes over 3,000 deaths in the U.K. annually.

“We have known for some time that aspirin increases the risk of bleeding for elderly patients. But our new study gives us a much clearer understanding of the size of the increased risk and of the severity and consequences of bleeds,” said lead author Professor Peter Rothwell.

“Previous studies have shown there is a clear benefit of short term anti-platelet treatment following a heart attack or stroke. But our findings raise questions about the balance of risk and benefit of long-term daily aspirin use in people aged 75 or over.”

Rothwell and his colleagues followed over 3,100 patients for 10 years who were prescribed a daily aspirin after a heart attack or stroke. For the patients under 65, the annual rate of bleeding severe enough to require hospitalization was about 1.5 percent. For patients aged 75-84, the annual rate rose to 3.5 percent and for patients over 85 it was 5 percent.

The researchers are not recommending that seniors stop taking aspirin. But they suggest that a proton-pump inhibitor – heartburn drugs – be prescribed along with aspirin to reduce the risk of bleeding.  They estimate that proton-pump inhibitors (PPIs) could reduce upper gastrointestinal bleeding by as much as 90% in patients receiving long-term aspirin treatment.

“While there is some evidence that PPIs might have some small long-term risks, this study shows that the risk of bleeding without them at older ages is high, and the consequences significant,” said Rothwell.

About half of adults aged 75 or older in the U.S. and Europe take aspirin or another anti-platelet drug daily .

FDA to Review All Abuse Deterrent Opioids

By Pat Anson, Editor

A week after asking that Opana ER be taken off the market, the head of the Food and Drug Administration has ordered a review of all opioid painkillers with abuse deterrent formulas to see if they actually help prevent opioid abuse and addiction.

The move is likely to add to speculation that the FDA may seek to prevent the sale of other opioid painkillers.

“We are announcing a public meeting that seeks a discussion on a central question related to opioid medications with abuse-deterrent properties: do we have the right information to determine whether these products are having their intended impact on limiting abuse and helping to curb the epidemic?” FDA commissioner Scott Gottlieb, MD, said in a statement.

Gottlieb said the FDA would meet with “external thought leaders” on July 10th and 11th to assess abuse deterrent formulas, which usually make medications harder for addicts to crush or liquefy for snorting and injecting. He did not identify who the thought leaders were.

“Opioid formulations with properties designed to deter abuse are not abuse-proof or addiction-proof. These drugs can still be abused, particularly orally, and their use can still lead to new addiction,” Gottlieb said. “Nonetheless, these new formulations may hold promise as one part of a broad effort to reduce the rates of misuse and abuse. One thing is clear: we need better scientific information to understand how to optimize our assessment of abuse deterrent formulations.”

In a surprise move last week, the FDA asked Endo Pharmaceuticals to remove Opana ER from the market, citing concerns that the oxymorphone tablets are being liquefied and injected. It’s the first time the agency has taken steps to stop an opioid painkiller from being sold.

“I am pleased, but not because I think that this one move by itself will have much impact,” Andrew Kolodny, MD, Executive Director of Physicians for Responsible Opioid Prescribing (PROP) told Mother Jones. “I’m hopeful that this signals a change at FDA—and that Opana might be just the first opioid that they’ll consider taking off the market. It’s too soon to tell.”

Opana was reformulated by Endo in 2012 to make it harder to abuse, but addicts quickly discovered they could still inject it. The FDA said Opana was linked to serious outbreaks of HIV, Hepatitis C and a blood clotting disorder spread by infected needles.

Endo has yet to respond to the FDA request. If the company refuses to stop selling Opana, the agency said it would take steps to require its removal from the market by withdrawing approval.

“The request to voluntarily remove the product is one thing, but it comes with a lot of other questions that are unanswered,” Endo CEO Paul Campanelli reportedly said at an industry conference covered by Bloomberg. “We are attempting to communicate with the FDA to find out what they would like us to do.”

Patient advocates say it would be unfair to remove an effective pain medication from the market just because it is being abused by addicts.

“The FDA is following a political agenda, rather than its mandate to protect the public health,” said Janice Reynolds, a retired oncology nurse who suffers from persistent pain. “Depriving those who benefit from the use of Opana ER to stop people from using it illegally is ethically and morally wrong.”

Sales of Opana reached nearly $160 million last year. The painkiller is prescribed about 50,000 times a month.

"This is something that could potentially apply to other drugs in the future, as it may signal a movement by the FDA to start taking products off the market that don't have strong abuse-deterrent properties," industry analyst Scott Lassman told CorporateCounsel.com.

The FDA put drug makers on notice four years ago that they should speed up the development of abuse deterrent formulas (ADF).  Acting on the FDA's guidance, pharmaceutical companies spent hundreds of millions of dollars developing several new opioid painkillers that are harder to chew, crush, snort or inject.

Were they worth the investment? Not according to a recent study funded by insurers, pharmacy benefit managers and some drug makers.

The Institute for Clinical and Economic Review (ICER), a non-profit that recommends which medications should be covered by insurance and at what price, released a report last month that gave ADF opioids a lukewarm grade when it comes to preventing abuse.

“Without stronger real-world evidence that ADFs reduce the risk of abuse and addiction among newly prescribed patients, our judgment is that the evidence can only demonstrate a ‘comparable or better’ net health benefit (C+),” the ICER report states.

The insurance industry has been reluctant to pay for ADF opioids, not because of any lack of effectiveness in preventing abuse, but because of their cost. A branded ADF opioid like OxyContin can cost nearly twice as much as a generic opioid without an abuse deterrent formula.  According to one study, OxyContin was covered by only a third of Medicare Part D plans in 2015. Many insurers also require prior authorization before an OxyContin prescription is filled.  

FDA Gives Fast Track Designation to New Pain Med

By Pat Anson, Editor

The U.S. Food and Drug Administration has granted “fast track” designation to a new, non-opioid pain medication for patients with osteoarthritis and chronic low back pain -- even though the drug has a history of safety issues.

Tanezumab is an investigational humanized monoclonal antibody that targets nerve growth factor (NGF), a protein that increases in the body as a result of injury, inflammation or chronic pain. Tanezumab binds to NGF and inhibits pain signals from reaching the spinal cord and brain.

Tanezumab is the first NGF inhibitor to receive fast track designation from the FDA, a process that speeds up the development and review of new therapies to treat serious conditions with unmet medical needs.

“If approved, tanezumab would be the first in a new class of non-opioid chronic pain medications,” said Ken Verburg, Chief Development Officer, Neuroscience & Pain, Pfizer Global Product Development. “We believe it would represent an important medical advance in the treatment of debilitating osteoarthritis and chronic low back pain for patients who do not experience adequate pain relief or cannot tolerate currently available pain medications.”

Pfizer is jointly developing tanezumab with Eli Lilly. The two drug makers are currently recruiting patients for Phase 3 studies of tanezumab in 7,000 patients with osteoarthritis, low back pain or cancer pain. Participants will be injected with tanezumab once every eight weeks for treatment periods ranging from 16 to 56 weeks, followed by a 24-week safety follow-up period.  Results from the clinical trials are not expected until next year.

"It is estimated that there are more than 27 million Americans currently living with osteoarthritis and 23 million living with chronic low back pain, many of whom fail to achieve adequate pain relief despite treatment with various types of pain medications,” said Christi Shaw, Senior Vice President and President, Lilly Bio-Medicines.

“We are committed to offering innovative solutions to people suffering from chronic pain conditions, and look forward to working closely with the FDA to facilitate the development of tanezumab.”

Ironically, it was the FDA that slowed the development of NGF inhibitors in 2010 because of safety concerns. The agency ordered a partial halt to clinical studies after Pfizer said a small number of osteoarthritis patients receiving tanezumab experienced worsening of their disease and needed joint replacements. Another safety issue arose in 2012 because the drug caused “adverse changes in the sympathetic nervous system of mature animals.” 

Most clinical studies of tanezumab did not resume until 2015. Pfizer says the current Phase 3 studies include risk mitigation measures for joint safety and sympathetic nervous system safety.

A clinical study of fasinumab, another nerve growth factor drug being developed by Teva and  Regeneron Pharmaceuticals, was stopped by the FDA last year after a patient showed signs of severe joint disease. Regeneron and Teva said they would redesign the study of patients with chronic low back pain to exclude participants with advanced osteoarthritis.

Fifth Georgia Overdose Linked to Fake Percocet

By Pat Anson, Editor

A fifth fatal overdose in Georgia has been linked to counterfeit painkillers being sold on the street as Percocet. 34-year old Robert Ketchup of Macon died Sunday in the intensive care unit of a hospital after he was found unconscious in his mother’s home on Thursday. According to the Atlanta Journal Constitution, Ketchup “had a bunch of pills on him.” 

In the past week, five deaths and dozens of hospitalizations have been linked to the yellow, oval shaped pills that have been circulating in central Georgia.

An analysis of the pills by the Georgia Bureau of Investigation found that they contained two synthetic opioids, cyclopropyl fentanyl and U-47700. The bureau says both drugs are “highly dangerous.”  

The U.S. Drug Enforcement Administration has been warning for over a year about counterfeit prescription drugs laced with fentanyl “inundating” the U.S. Until now, most of the fake pills have been disguised to look like the painkiller oxycodone or Xanax, an anti-anxiety medication.

“The counterfeit pills have the numbers 10/325 on one side and the word PERCOCET in all capital letters on the opposite side. On the counterfeit pills the word PERCOCET is not stamped as deep as the manufacturer typically does on their pills. Also on the counterfeit pills, the imprint of the name is also at an angle,” the Bibb County Sheriff's Office said in a statement. “Everyone is strongly encouraged to treat these pills or anything resembling these pills as hazardous.”

No arrests have been made and the source of the counterfeit pills is still unknown.  

Fentanyl is a synthetic opioid that is 50 to 100 times more potent than morphine and can be lethal in very small doses. It is available legally by prescription in patches, lozenges and sprays to treat severe pain, but illicitly manufactured fentanyl smuggled in from Mexico and China is blamed for thousands of overdose deaths in the U.S. and Canada.

Unsuspecting buyers, including some pain patients who were unable to get opioid medication legally, have no idea the drug they’re getting from a dealer or friend could be lethal.

"Mexican drug cartels are manufacturing fentanyl into Percocet pills, and oxycodone and other type pills as well, but it's a way for these bad people to make a very good living on the backs of addiction and that's what they are targeting," said DEA Special Agent in Charge Dan Salter.

The fentanyl problem appears to be growing worse, as even small-time drug dealers realize they can easily order the chemicals needed to make fentanyl, manufacture their own fake pills, and make millions of dollars selling them on the black market.

Last week federal agents seized 50 kilograms of N-Phenethyl-4-piperidinone (NPP), a fentanyl precursor, from a storage facility in Northborough, Massachusetts. Some of the boxes seized were marked UPS and “priority mail.” Others were labeled with Chinese characters.

If converted, the NPP could have theoretically been used to make 19 million fentanyl tablets, with a street value of $570 million.

dea photo

Nearly 80 percent of the people who died of an overdose in Massachusetts last year ingested fentanyl.

Trump Opioid Commission to Hold First Meeting

By Pat Anson, Editor

The pain community will get its first glimpse this month at how the Trump administration may address the nation’s opioid crisis, when the president’s new Drug Addiction and Opioid Commission holds its first two meetings.

The commisison's first meeting will be held Friday June 16, followed by a teleconference on Monday June 26. Both meetings are open to the public.

Details on how to watch or listen to the meetings can be found in the Federal Register, here and here.

Chaired by New Jersey Governor Chris Christie, the commission will make recommendations to the president later this year on how to combat drug abuse, addiction and the overdose crisis, which is blamed for over 50,000 deaths in 2015.

The White House says the commission will “work closely” with President Trump’s son-in-law and senior advisor, Jared Kushner.

“I made a promise to the American people to take action to keep drugs from pouring into our country and to help those who have been so badly affected by them. Governor Christie will be instrumental in researching how best to combat this serious epidemic and how to treat those it has affected,” Trump said in a statement.  

The public can submit written comments to the commission by emailing the Office of National Drug Control Policy at commission@ondcp.eop.gov.

“I'd really like to see the commission recognize that addressing opioid use disorders through increasing access to treatment and through attempting to reduce the supply of opioids (both legal and illegal) will only go so far, and that, to be truly successful, they also must address inadequacies in the way we treat pain,” said Bob Twillman, PhD, Executive Director of the Academy of Integrative Pain Management, which represents pain management physicians.

“Unless and until we reach a point where we can truly implement the kind of integrative pain care called for by every guideline and highlighted in the National Pain Strategy, we are going to be unable to succeed in addressing both of the public health crises we are encountering.”

Twillman helped draft and submit a letter to the commission signed by 73 different medical and patient advocacy groups calling for more federal funding of pain research and treatments.

“This longstanding underinvestment in pain research has resulted in a limited number of safe and effective chronic pain treatments, and according to the FDA, a field that is 'strikingly deficient' in high-quality evidence to assess risks and benefits of current treatments,” the letter states. “As a result, even highly knowledgeable health care providers are left without clear guidance, and may spend months to years with their patients experimenting with treatments in the hope of finding relief.”

Richard Martin, a retired Nevada pharmacist disabled by chronic back pain, says the first item on the commission’s agenda should be to withdraw and re-write the CDC’s opioid guideline, which discourages physicians from prescribing opioids for chronic pain.

“Since the Guideline was released, there are now tens of thousands of non-cancer pain patients on long term opioid prescription therapy who are being INVOLUNTARILY tapered down or off of their pain medications.  This has resulted in patients being under treated, left to suffer with debilitating pain.  Some of these patients have had their opioid medications abruptly discontinued throwing them into withdrawal,” Martin wrote in an email to the commission.

“There now abounds significant anecdotal evidence and significant documented media reports, that these patients who have been involuntarily tapered down or off their opioid medications, are committing suicide due to the intense pain that has resulted.” 

Background of Commission Members

In addition to Gov. Christie and Jared Kushner, the president has appointed to the commission Gov. Charlie Baker of Massachusetts, Gov. Roy Cooper of North Carolina, Bertha Madras, PhD, a professor of psychobiology at Harvard Medical School, and Patrick Kennedy, a former Rhode Island congressman. No pain patients, pain management experts or practicing physicians were appointed to the panel.

Gov. Christie, who lost a close friend to painkiller addiction, has seen his home state of New Jersey ravaged by the opioid crisis, with 1,600 overdose deaths in 2015.  Christie championed a new state law that limits opioid prescriptions for acute pain to just five days.  

Gov. Cooper supports similar legislation now under consideration in North Carolina.  Over 1,100 North Carolinians died from opioid overdoses in 2015, with prescription opioids involved in about half of them.

Gov. Baker’s home state of Massachusetts lost over 2,000 people to opioid overdoses in 2016, most of them caused by heroin and illicit fentanyl. Baker apparently got an inside track on the commission when he discussed the opioid crisis with Ivanka Trump while sitting next to her during a National Governors Association dinner.

Bertha Madras recently authored an editorial in JAMA Psychiatry in which she claimed that prescription opioids “remain a primary driver of opioid-related fatalities” and called on the medical community to limit the supply of opioid medication.

Patrick Kennedy has battled substance abuse issues since he was teenager, including addiction to the painkiller OxyContin. He now works for Advocates for Opioid Recovery, a non-profit funded in part by Braeburn Pharmaceuticals, which makes an implant that dispenses the addiction treatment drug buprenorphine.

Genetic Testing Company Raided by FBI

By Pat Anson, Editor

FBI agents have raided the headquarters of Proove Biosciences, a controversial genetic testing company that claims its DNA tests can improve the effectiveness of pain management and determine whether a patient is at risk of opioid addiction.

Over two dozen FBI agents appeared at Proove offices in Irvine, California Wednesday as part of a healthcare fraud investigation. They were later seen carrying dozens of boxes out of two buildings

“It is an ongoing investigation out of our San Diego office. It involves healthcare fraud. And unfortunately we are unable to say anything more about it at this time. The affidavit supporting the search warrant is under seal,” Cathy Kramer, an FBI special agent, told KABC-TV.

STAT News reported in February that the FBI and the Inspector General for the Department of Health and Human Services (HHS) were investigating possible criminal activity at Proove.

Former and current employees who were interviewed by the FBI told STAT the agents were focused on possible kickbacks to doctors who encouraged patients to take Proove’s DNA tests. Physicians reportedly could make $144,000 a year in kickbacks that were called “research fees.”

The HHS Inspector General issued a Special Fraud Alert in 2014 warning physicians that any payments, referrals, rent or reimbursements from lab testing companies could be seen as violations of anti-kickback laws.

Proove promotes itself as the “leader in personalized pain medicine” and claims its genetic tests can identify medications that would be most effective at treating pain. The company recently claimed that 94% of patients experienced significant pain relief within 60 days of treatment changes recommended by Proove. Critics say most Proove studies are not peer-reviewed and one genetic expert has called them “hogwash.”

According to STAT, doctors affiliated with Proove in California, Florida and Kentucky were also raided by the FBI. Proove said it was cooperating with the investigation, and that no arrests or charges have been made.

"Proove has been subject to a handful of inaccurate stories initiated by STAT News that we believe have contributed to this latest action," the company said in a statement. "While we originally chose not to dignify these outlandish accusations with a response, we now understand that we can no longer ignore these false stories based on unreliable sources, and filled with erroneous accusations... spread by a few disgruntled former employees and consultants.  Proove is confident that the facts supported by verifiable and reliable sources will clearly restore our reputation."

Proove Linked to Montana Pain Clinic

Proove is the second laboratory testing company raided by the FBI that has been linked to Benefis Pain Management Center, a pain clinic in Great Falls, Montana. 

As PNN has reported, FBI agents last November raided the offices of Confirmatrix Laboratories near Atlanta. Two days later, the company filed for Chapter 11 bankruptcy protection. Confirmatrix was founded by Khalid Satary, a convicted felon and Palestinian national that the federal government has been trying to deport for years.

In 2013, Medicare identified Confirmatrix as the most expensive urine drug testing lab in the country, charging an average of $2,406 for each Medicare patient.

Benefis has continued to send urine drug samples to Confirmatrix for testing even after the company filed for bankruptcy. Some Benefis patients have recently been contacted by collection agencies seeking payment for urine tests costing well over $1,000 that their insurance refused to pay for. Similar tests by other labs cost only a few hundred dollars.

According to its bankruptcy filing, Confirmatrix has 152 employees in 15 different states, including one employee in Montana who apparently works on site at the Benefis pain clinic. PNN has also learned that Proove Biosciences has had employees working at the clinic. A Proove “patient engagement representative” was employed there as early as May 2016.

“We had a meeting one day and here are these people from Proove Biosciences. They told us they were doing a research project,” says Rodney Lutes, a physician assistant (PA) who was later fired by Benefis. “They wanted to come to Benefis, into the pain department, and test our patients.  We were told this would be at no cost to the patient. My understanding was that they weren’t going to charge anybody, but I found out afterwards they were charging insurance companies.

“They said providers who participated in this would get some form of payment for participating in the program and for filling out all the paperwork.  What they did is they had a technician there in the department and every day I would get a list from that technician of patients that they would like to try to include in the program.”

Lutes says he recommended the DNA test to many of his patients, but never received any money from Proove. He says some of his patients later complained that their insurance was billed for the DNA test.

“One of the things that bothered me was that I signed a lot of the papers, but they also had my supervising doc on all of those papers,” Lutes told PNN. “I also felt like she was the one that brought them (Proove) in there.”

Lutes is referring to Katrina Lewis, MD, a pain management specialist at Benefis who is listed as a member of Proove’s Medical Advisory Board.  Lewis plays a significant role at the pain clinic even though she only works there part time. 

“Dr. Lewis works for Benefis one week a month and has been instrumental in the development of our multidisciplinary approach and current protocols,” said Keri Garman, Director of Corporate Communications at Benefis.

In a statement emailed to PNN last month, Lewis said regular urine drug testing was necessary to ensure that “appropriate levels” of medication are present. Current clinic policy is that “high risk” patients should have a urine test at least once every two months.

“Presence of too high of a level of opioids or other substances in the urine can make it inappropriate and unsafe to continue prescribing opioids.  Presence of none of the prescribed opioids in the urine indicates the care plan is not being followed and further prescribing is medically unnecessary,” Lewis said.

Benefis: No Kickbacks from Testing Labs

PNN has made repeated requests to Benefis to clarify its relationship with Confirmatrix and Proove, and whether Lewis or any other Benefis employees were receiving compensation from the laboratories for referring business to them. 

“Benefis and its employees, including Dr. Katrina Lewis, do not receive kickbacks from Confirmatrix or Proove. As for any questions you have regarding the lab business practices of these facilities, these would be best answered by the companies directly,” Benefis spokesman Ben Buckridge said in a statement emailed to PNN last week. 

“We take these accusations and defamatory statements against our organization and staff seriously. We appreciate your diligence on this issue.” 

In an earlier statement, a Benefis official said the DNA tests are voluntary and only done on patients if they are appropriate.

“Patients have the option to decline this testing, however, it proves to be very helpful in determining treatment plans for our patients in many cases. This testing has not been readily available until recently,” said Kathy Hills, Chief Operating Officer of Benefis Medical Group.

“Genetic testing allows us to see if the patient is appropriately synthesizing specific medications and can drastically alter treatment plans, showing us that sometimes the medications are not effectively metabolizing and therefore not as effective, which is why some patients have needed high doses. Our partners in this have an extensive patient assistance program that waives many costs, and patients are not penalized or removed from opioids if they refuse to have a genetic test performed.”

But a recent copy of the clinic’s opioid policy obtained by PNN says the tests are not voluntary for everyone. 

“All patients on dosing levels at or higher than the maximum policy dose MUST be submitted for genetic testing,” the policy states. The word "must" is capitalized in the document. 

One Benefis patient who took the DNA test said Lutes recommended it.

“He said everyone was doing it and that the insurance would be billed, but if they did not pay for it then Benefis would. I think he said something about it being a $6,000 test,” she told PNN.  “To me it was a waste of time and money. The meds it said I should be taking either didn’t work, stopped working, or made me sick. And the meds I should not be taking I do just fine on.”

It is not clear whether the pain clinic's association with Proove or Confirmatrix had anything to do with Lutes’ firing in March. The 68-year old Lutes treated several hundred pain patients and was popular with many of them. 

Lutes was discharged for violating Benefis policy about record keeping, opioid dosage and urine drug testing, but feels he was “written up for violations that do not exist.” His supervising physician – Katrina Lewis – also requested removal from that role, meaning Lutes could no longer practice at Benefis as a physician assistant.

Since his dismissal, many of Lutes former patients who were on relatively high doses of opioids say their medication has been reduced or stopped entirely. One patient, whose opioid dose was cut significantly, committed suicide. Still others complain they were labeled and treated as addicts by clinic doctors and staff, and now have trouble finding new physicians in the Great Falls area. The ones who remain at Benefis say they are being told to take new tests and exams. 

Benefis says it cannot comment on the accusations because of patient and employee privacy rights.

“Unless Rodney Lutes, PA, or the patients with whom you are speaking will sign written releases allowing us to comment fully on the facts of their employment or their care, respectively, we are simply unable to engage in any further back and forth discussions.  We have provided all the information we are able given the legal limitations governing our industry,” Buckridge said.

FDA Wants Opana ER Sales Stopped

By Pat Anson, Editor

The U.S. Food and Drug Administration today asked Endo Pharmaceuticals to remove Opana ER from the market, citing concerns about safety risks when the tablets are liquefied and injected. It’s the first time the agency has taken steps to stop an opioid painkiller from being sold -- and oddly it has more to do with preventing HIV and Hepatitis C than it does in preventing opioid abuse.

“We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”

Opana ER is the brand name for Endo’s extended release opioid painkiller oxymorphone. It was first approved by the FDA in 2006 for the management of moderate to severe pain.  In 2012, after numerous reports that it was being abused and sold on the black market, Opana was reformulated by Endo to make it harder for addicts to crush or liquefy.

That same year, over a dozen cases of a serious blood clotting disorder and Hepatitis C in intravenous drug users were linked to the reformulated Opana in Tennessee. But it took another five years for the FDA to act.

In March, an FDA advisory panel voted 18-8 that the benefits of reformulated Opana no longer outweighed its risks. The agency found“a significant shift in the route of abuse” from snorting to injection. Injecting Opana was associated with outbreaks of HIV, Hepatitis C and a blood clotting disorder called thrombotic thrombocytopenic purpura. All can be spread intravenously by infected needles.

“The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research. “This action will protect the public from further potential for misuse and abuse of this product.”

The FDA has requested that Endo voluntarily remove Opana from the market. Should the company refuse to do so, the agency intends to take steps to formally require its removal by withdrawing approval.

"Endo is reviewing the request and is evaluating the full range of potential options as we determine the appropriate path forward," the company said in a statement. "Despite the FDA's request to withdraw Opana ER from the market, this request does not indicate uncertainty with the product's safety or efficacy when taken as prescribed. Endo remains confident in the body of evidence established through clinical research demonstrating that Opana ER has a favorable risk-benefit profile when used as intended in appropriate patients."

According to Bloomberg, sales of Opana  reached nearly $160 million last year, about 4 percent of the company’s total revenue.

WHO Lists Fentanyl as ‘Essential Medicine’

By Pat Anson, Editor

At a time when hundreds – perhaps thousands – of Americans and Canadians are dying every month from overdoses of illicit fentanyl mixed with heroin or turned into counterfeit painkillers, it’s easy to lose sight of the fact that prescription fentanyl is an important and useful analgesic.  

We were reminded of that today by the World Health Organization (WHO), which added fentanyl skin patches and methadone to its list of essential medicines for treating cancer pain. WHO’s Essential Medicine List is not widely followed in developed countries – where prescription drugs are widely available – but it is used in many third world countries to guide decision making and increase access to medicines that are often in short supply.

"Safe and effective medicines are an essential part of any health system," said Dr. Marie-Paule Kieny, WHO Assistant Director-General for Health Systems and Innovation. "Making sure all people can access the medicines they need, when and where they need them, is vital to countries’ progress towards universal health coverage."

Fentanyl patches and methadone are two of the 30 drugs being added to the Essential Medicine List, raising the total to 433 medicines considered vital in addressing public health needs. WHO also added drugs for treating HIV, hepatitis C, tuberculosis and leukemia; and gave new advice about the use of antibiotics.

While illicit, black market fentanyl has become a deadly scourge across the U.S. and Canada, prescription fentanyl is legally available in patches, lozenges and sprays to treat severe pain.  

WHO’s inclusion of fentanyl patches and methadone on the essential list is limited to the treatment of cancer pain. An expert panel that reviewed the medicines noted “there is a need for additional opioid treatment options” for cancer pain. About a third of cancer patients worldwide are undertreated for pain, and patients living in low or middle income countries often have limited access to opioid painkillers.  

Other opioids already on the essential list (for treating pain and palliative care) are codeine, morphine, hydromorphone and oxycodone . Aspirin, ibuprofen and paracetamol (acetaminophen) are on it too, although the latter is “not recommended for anti-inflammatory use due to lack of proven benefit.”

Gabapentin Rejected

It’s also worth noting the medications that did not make the updated WHO list. Tramadol was not approved as a treatment for cancer pain, while gabapentin (Neurontin) was rejected as a treatment for neuropathic pain.

WHO’s expert panel gave a scathing review of the application made by the International Association for the Study of Pain and the International Association of Hospice and Palliative Care for the inclusion of gabapentin; noting there were many cases of bias and data manipulation in the clinical studies used to support it. Also noted was the $430 million fine paid by Pfizer in 2004 to settle civil and criminal charges for a “marketing scheme” to promote Neurontin for unapproved uses.    

“The Committee acknowledged the serious issues on publication and outcome reporting bias as important ones,” the panel said. “The Expert Committee considered the uncertainty in efficacy estimates as a result of publication and outcome reporting biases in the currently available evidence for gabapentin. The Committee did not recommend inclusion of gabapentin on the EML (Essential Medicine List) for neuropathic pain on the basis of its uncertain benefits.”

While gabapentin is approved for neuropathic pain in the European Union and Australia, it is only approved for epilepsy and neuropathic pain caused by shingles in the U.S. Despite that limitation, gabapentin is widely prescribed “off label” to treat depression, anxiety, migraine, fibromyalgia and other chronic pain conditions.  About 64 million prescriptions were written in the U.S. for gabapentin in 2016, a 49% increase since 2011.

Utah Raid Uncovered Large Fentanyl Pill Ring

By Pat Anson, Editor

A drug bust in a Utah home last November has uncovered one of the largest counterfeit pill operations in U.S. history.

This week a federal grand jury in Salt Lake City indicted six individuals for manufacturing nearly 500,000 pills laced with illicit fentanyl that were disguised to look like the painkiller oxycodone and the anti-anxiety drug alprazolam (Xanax). The counterfeit pills were distributed throughout Utah and the United States to customers who ordered them online.

Fentanyl is a powerful synthetic opioid that it is 100 times more potent than morphine and 50 times more potent than heroin. In recent years, illicit fentanyl has been blamed for thousands of overdose deaths in the U.S. and Canada.

“What we feared and hoped somehow would stay away has arrived in spades,” said Brian Besser, the DEA’s agent in charge in Utah. “Fentanyl is as dangerous as it gets.”

According to documents filed in federal court, the pill ring was created by Aaron Shamo and Drew Crandall, both Utah residents who worked together at eBay, but quickly grew to include the other conspirators. Prosecutors say the defendants purchased pill presses, dies and stamps so the counterfeit pill markings would match those of legitimate pharmaceutical drugs. Some items were purchased legally and others, such as fentanyl and alprazolam, were illegally imported from China

The fake pills were sold on a “dark net online store” at a significant profit. Once sold, Shamo and Crandall used their co-conspirators to package the pills and ship them to customers. In less than a year, the operation mailed 5,606 drug orders totaling $2.8 million, according to court documents.

“Shamo’s customer base was extremely comprehensive and widespread, touching every corner of the United States,” Besser said. “It touched large cities and rural communities.”

The round blue tablets manufactured by the pill ring were offered for sale online as oxycodone 30mg tablets. The tablets were debossed with “A 215” on the bisected side, with an “M” on one side and a “30” above the bisect on the other side. The indictment alleges the defendants did not use oxycodone at all in the manufacturing process, but instead used illicit fentanyl.

Federal agents arrested Shamo last November. During a raid on Shamo’s suburban Salt Lake City home, agents discovered a pill press capable of manufacturing several thousand pills an hour. Agents also seized 70,000 pills and $1.2 million in cash stuffed in garbage bags.

Crandall fled to Australia with his girlfriend and was in Laos when agents raided Shamo’s house. He was arrested last month in Hawaii. A summons will be issued for the other four conspirators for their initial appearances in federal court.