Use of NSAIDs Risky for Osteoarthritis Patients

By Pat Anson, PNN Editor

It’s long been known that nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen can raise the risk of cardiovascular problems. A large new study in Canada has documented how NSAIDs can significantly raise the risk of heart disease, congestive heart failure and stroke in people with osteoarthritis.

Osteoarthritis (OA) is a joint disorder that leads to thinning of cartilage and progressive joint damage. NSAIDs are frequently used to treat the pain and inflammation caused by OA.

The Canadian study, published in the journal Arthritis & Rheumatology, looked at nearly 7,750 osteoarthritis patients in British Columbia and compared them with a control group of over 23,000 patients without OA. The average age of the participants was 65 and a little over half were women.

The risk of developing cardiovascular disease was found to be about 23% higher among people with OA than the control group. Researchers attributed about 41% of that increased risk to the use of NSAIDs.

NSAIDs appeared to play a significant role in several cardiovascular problems. The risk of congestive heart failure was 42% higher among people with OA, followed by a 17% greater risk of heart disease and a 14% greater risk of stroke.

"To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and cardiovascular disease in a large population-based sample," said senior author Aslam Anis, PhD, of the School of Population and Public Health at the University of British Columbia.

"Our results indicate that osteoarthritis is an independent risk factor for cardiovascular disease and suggest a substantial proportion of the increased risk is due to the use of NSAIDs. This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis."

The association of cardiovascular disease with NSAIDs is consistent with previous research.  A large international study in 2017, for example, found that prescription strength NSAIDs raises the risk of a heart attack as soon as the first week of use.

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products, including cold and flu remedies. They are found in so many products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Canada adopted guidelines in 2017 that recommend NSAIDs as an alternative to opioid pain medication. The guideline makes no mention of the health risks associated with NSAIDs, but focuses on their cost effectiveness.

“NSAID-based treatment may have lower mean costs and higher effectiveness relative to opioids,” the guideline states. “Naproxen-based regimens in particular may be more cost effective compared to opioids and other NSAIDs, such as ibuprofen and celecoxib.”

Opioid guidelines released in 2016 by the U.S. Centers for Disease Control and Prevention also recommend NSAIDs as an alternative to opioids, but acknowledge the medications “do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks.”

In 2015, the Food and Drug Administration ordered warning labels for all NSAIDs to indicate they increase the risk of a fatal heart attack or stroke. The FDA warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at risk of heart failure. People already diagnosed with heart failure should refrain from using NSAIDs altogether.

CDC: Still Not Enough Naloxone

By Pat Anson, PNN Editor

The Trump Administration is stepping up efforts to increase prescribing of naloxone, an overdose recovery drug credited with saving thousands of lives.

Although naloxone prescriptions have increased dramatically, a new CDC Vital Signs report estimates that nearly 9 million additional prescriptions could have been dispensed last year if every patient with a high-dose opioid prescription was offered naloxone.  Patients are considered “high risk” if they take an opioid dose of 50 morphine milligram equivalent (MME) or more per day.

Naloxone has been used for years by first responders and emergency medical providers to revive overdose victims. Current efforts are focused on expanding access to the drug by prescribing it directly to patients considered at risk of an overdose.

In 2018, CDC researchers say only one naloxone prescription was dispensed for every 70 high-dose opioid prescriptions nationwide. Naloxone “under-prescribing” was even more acute in rural counties, which are nearly three times more likely to be ranked low in naloxone dispensing than metropolitan counties.

“It is clear from the data that there is still much needed education around the important role naloxone plays in reducing overdose deaths. The time is now to ensure all individuals who are prescribed high-dose opioids also receive naloxone as a potential life-saving intervention,” CDC Director Robert Redfield, MD, said in a statement.

Ironically, federal policies contribute to the under-prescribing. In 2018, most (71%) Medicare prescriptions for naloxone required a copay, compared to 42% for commercial insurance.

In January, the Food and Drug Administration encouraged drug makers to make naloxone available over-the-counter without a prescription. The FDA even developed an OTC label for Narcan, a naloxone nasal spray that sells for about $135. Seven months later, the FDA could not confirm to PNN that any company had submitted an application for an OTC version of naloxone.

Last year the Department of Health and Human Services released guidance urging doctors to “strongly consider” prescribing naloxone to patients on any dose of opioids when they also have respiratory conditions or obstructive sleep apnea, are co-prescribed benzodiazepines, have a mental health or substance abuse disorder, or a history of illegal drug use or prescription opioid misuse.

Many states are also taking steps to increase naloxone prescribing. California now requires doctors to “offer” naloxone prescriptions to pain patients deemed at high risk of an overdose. State law does not make the prescriptions mandatory, yet some patients say they were “blackmailed” by pharmacists who refused to fill their opioid scripts unless naloxone was also purchased. Patients around the country report similar experiences.   

Unintended Consequences

The drumbeat for naloxone comes at a time when sales are already booming. There were 556,000 naloxone prescriptions in 2018, twice as many as in 2017.

There’s no doubt naloxone saves lives, but some researchers say the drug has had little effect on the overdose crisis and may in fact be making it worse. In a recent study published by SSRN, two economics professors warned of “unintended consequences” if naloxone becomes more widely available.

“We expect these unintended consequences to occur through two channels. First, the reduced risk of death makes opioid abuse more appealing, leading some to increase their opioid use — or use more potent forms of the drug — when they have naloxone as a safety net. Some of those abusers may become criminally active to fund their increased drug use,” wrote Jennifer Doleac, PhD, Texas A&M University, and co-author Anita Mukherjee, PhD, University of Wisconsin.

“Furthermore, expanding naloxone access might not in fact reduce mortality. Though the risk of death per opioid use falls, an increase in the number or potency of uses means the expected effect on mortality is ambiguous.”

The researchers said there were anecdotal reports of “naloxone parties” where attendees used heroin and prescription opioids to get high knowing they could be revived. News reports have also quoted first responders who are frustrated that the same opioid abusers “are saved again and again by naloxone without getting treatment.”

Co-Pay Assistance Programs Fail to Help Uninsured Patients

By Pat Anson, PNN Editor

Co-pay assistance programs – also known as co-pay charities – are ostensibly designed to help needy patients pay for prescription drugs. But a new study by researchers at the Johns Hopkins Bloomberg School of Public Health found that nearly all co-pay programs fail to cover uninsured patients who need financial help the most.

The researchers also found that co-pay programs were more likely to cover high-cost, brand-name prescription drugs, despite the availability of lower-priced generic medications. The findings are published online in JAMA.

“Independent patient assistance programs favor higher-priced drugs, and the higher the drug price, the higher the likelihood of it being covered,” says co-author Gerard Anderson, PhD, professor in the Bloomberg School’s Department of Health Policy and Management. “Unfortunately patients with the greatest financial needs -- people without health insurance -- do not qualify for these programs.”

Anderson and his colleagues looked at the six largest charity organizations, which ran 274 different patient assistance programs in 2018.

Most of the programs only covered drugs for cancer-related conditions or genetic and rare diseases. None offered free drugs and typically they only covered the most expensive medications.

“Only covering insured patients may help these programs cover more patients with their limited funds,” said lead author So-Yeon Kang, MPH, a research assistant in the Bloomberg School’s Department of Health Policy and Management. “But leaving out the uninsured diminishes the charitable aspects of these organizations supported by tax-exempted donations.”

Misconduct Widespread

Patient assistance programs run by independent charities are usually funded by pharmaceutical companies. Federal investigations into several co-pay assistance programs led to multimillion-dollar settlements with drug companies for allegedly steering patients to their higher-priced drugs.

Over the past year, Pfizer, Amgen, Jazz Pharmaceuticals, Astellas Pharma, Lundbeck and Alexion have all paid heavy fines to settle allegations that they used co-pay programs to defraud Medicare. Federal anti-kickback laws prohibit pharmaceutical companies from making any kind of payment to induce Medicare patients to purchase their drugs. The prohibition includes co-pays.

“We are committed to ensuring that pharmaceutical companies do not use third-party foundations to pay kickbacks masking the high prices those companies charge for their drugs,”  U.S. Attorney Andrew Lelling said in a statement. “This misconduct is widespread, and enforcement will continue until pharmaceutical companies stop circumventing the anti-kickback laws to artificially bolster high drug prices, all at the expense of American taxpayers.”

Similar allegations were made against Insys Therapeutics and the “Gain Against Pain” co-pay program run by the U.S. Pain Foundation. Insys donated over $3.1 million to U.S. Pain, with most of the money going to its co-pay program to help patients pay for Subsys, an expensive fentanyl spray made by Insys. A four-day supply of Subsys can cost nearly $24,000.

The founder of Insys and four former executives were recently found guilty of racketeering charges unrelated to the co-pay program. The company also agreed to pay $225 million in fines and penalties to settle criminal and civil investigations. U.S. Pain ended the “Gain Against Pain” program in 2018 and said it would no longer accept funding from Insys.

In an editorial, Katherine Kraschel, a lecturer at Yale Law School, and Gregory Curfman, MD, deputy editor of JAMA, called for more oversight of co-pay programs to make sure they help patients who truly need it.

“Although patient assistance programs may provide important financial relief for patients, the current patient assistance program structure largely neglects uninsured individuals,” they wrote.  “Absent other regulatory interventions, the Department of Justice needs to continue to scrutinize patient assistance program practices, and the Internal Revenue Service and state attorneys general should examine the tax-exempt status of patient assistance programs.”

Would Decriminalization Solve the Overdose Crisis?

By Pat Anson, PNN Editor

Vancouver, British Columbia was the first major North American city to be hit by the overdose crisis. In 2016, after a wave of overdose deaths involving illicit fentanyl and even more deadly synthetic opioids like carfentanil, the western Canadian province declared a public health emergency.

Despite efforts to decrease the supply of prescription opioids in BC, over 3,600 more people have overdosed since the emergency was declared, with fentanyl detected in 87% of the deaths last year.

So when BC’s largest healthcare system recommends some radical solutions to the overdose crisis, it’s worth noting. Vancouver Coastal Health (VCH) released a report last month recommending that illegal drugs be decriminalized and that drug users be given access to prescription opioids as an alternative to the black market.

"Legalization and regulation of all psychoactive substances would reduce people's dependence on the toxic illegal supply, criminal drug trafficking and illegal activities that people with addictions must engage in to finance their drug use," said Dr. Patricia Daly, VCH’s chief medical health officer.  

Some Canadian drug policy experts think the idea makes sense.

"The illegal market is an absolute toxic mess right now," Donald MacPherson, executive director of the Canadian Drug Policy Coalition, told the CBC. "It's really in line with consumer protection strategy ... just like we do with every other substance that we ingest, whether it be food or drugs."

Also notable about the VCH report is that – unlike most regulators and politicians in Canada and the U.S. – prescription opioids are not singled out as the root cause of the overdose crisis. Instead, opioid medication is seen as part of the solution.

The report recommends pilot programs to see if prescription fentanyl and other opioid medications made available at supervised consumption sites could help high-risk illicit drug users “transition” to legal opioids.

“Piloting legal access to opioids is different from OAT (opioid agonist therapy) as treatment and would be low-barrier and flexible. Initial pilots would include observation of consumption, followed by pilots allowing distribution of opioids for people to take away for later consumption,” the report recommends.

The idea is controversial, but some doctors are warming up to it. A pilot program recently began at a Vancouver clinic, where hydromorphone tablets are given to about 50 patients who ingest them on site under staff supervision. In Ontario, over 400 healthcare providers and researchers recently signed an open letter asking that high dose injectable hydromorphone be made widely available to illicit drug users.

Substance Abuse and Socioeconomic Problems

The primary cause of the opioid crisis, according to the VCH report, is a “complex interaction” of socioeconomic problems, such as unemployment and homelessness, combined with substance abuse and an increasingly dangerous black market supply.

VCH analyzed the deaths of 424 overdose victims from 2017 and found that less than half (45%) even sought treatment for acute or chronic pain. They were far more likely to be unemployed (72%) and have a substance abuse problem (84%). About four out of ten overdose victims used opioids, alcohol or stimulants daily.

“Most of those who died used multiple substances including opioids, alcohol and stimulants such as cocaine and crystal meth. A significant percentage of those who died of opioid overdoses had primary alcohol use disorder and/or stimulant use disorder,” the report found.

Importantly, most of those who died were no strangers to the healthcare system. The vast majority (77%) had seen a healthcare provider in the year before they overdosed and one out of five (21%) had seen a provider a week before their death. Six out of ten (59%) had received Suboxone or methadone to treat opioid addiction, but the medications were either not effective or they dropped out of treatment.

In addition to decriminalization, the VCH report recommends improving access to addiction treatment, better substance abuse training of healthcare providers, and increased access to the overdose reversal drug naloxone.

Lessons from the Opioid Database

By Roger Chriss, PNN Columnist

Last month The Washington Post made public for the first time a DEA database of opioid prescribing that shows “the path of every single pain pill” sold in the United States from 2006 to 2012.

The Post’s analysis showed that 76 billion pills flowed through the country and nearly 100,000 fatal overdoses occurred over a seven-year period.

Biospace explained that opioid manufacturers, distributors and retailers “allowed the drugs to reach the streets of communities large and small, despite persistent red flags that those pills were being sold in apparent violation of federal law and diverted to the black market.”

The first lesson from the database seems obvious. Too many pills were prescribed, with opioid manufacturers, distributors and retailers failing to report suspicious orders and government agencies failing to oversee the prescription opioid supply.

“If you don’t start millions of opioid-naive people on opioids they don’t need, it translates … in the longer term into fewer overdoses,” Stanford psychiatry professor Keith Humphreys told the Post.

But this misses a key lesson. Although no drug should ever be used when it is not needed, this leaves open the obvious and essential question: How do we reduce risks in people who do need opioids?

We cannot ban opioids completely without returning to pre-Civil War medicine. But each year we have millions of car crashes, severe battlefield and workplace injuries, new cases of cancer, major surgeries and devastating long-term illness.

In the many commentaries on the opioid database, little has been said about improving prescribing safety. We need better ways to use opioids safely because sometimes we just don’t have any other option.

If it is true, as Julie Croft, an Oklahoma addiction treatment provider wrote, “We are all just one accident away from becoming addicted to painkillers” -- then we had better rapidly improve how we use opioids or come up with better alternatives since we have millions of accidents annually.

To this end, Yale and the Mayo Clinic were recently awarded a $5.3 million FDA grant to study patients with acute pain and their use of opioids.

Reduced Prescribing May Not Be Enough

The next lesson in the database is vulnerability to substance abuse. Dennis Scanlon, PhD, and Christopher S. Hollenbeak, PhD, note in the American Journal of Managed Care, that “although using government or regulatory mechanisms to prevent or significantly curb the supply of addictive narcotics is certainly valuable, there is also value in preventing or reducing addiction at its core.”

In other words, policies that reduce opioid prescribing may be helpful, but they may also not be enough. We need better tools and greater understanding of opioid prescribing. The National Institute of Drug Abuse currently estimates that 8% of people on long-term opioid therapy develop some form of opioid use disorder, while The BMJ estimates that less than 1% of surgical patients receiving opioids face a similar fate. These numbers may seem low, but every effort should be made to reduce them.

As bioethicist Travis Reider states in his book “In Pain” about his personal struggle with opioids: “The bottom line is that we are not, by and large, acting decisively in an evidence-based way to tackle the myriad problems raised by opioids. Although we don’t know everything about how to turn the corner on this crisis, we know a lot, and we’re simply not doing it.”

The last essential lesson from the opioid database is that opioid abuse and addiction came long before the crisis. The clichéd response that we “cannot arrest our way” out of the crisis needs to be extended to we “cannot simply restrict our way out” either. We need better prevention and early intervention for opioid use disorder, and improved management of the opioid supply chain so as to prevent theft and diversion.

The crisis is a fast-moving target, with prescription opioid levels having dropped significantly since 2012. Overdoses involving prescription opioids have also fallen, while deaths linked to illicit opioids like fentanyl, cocaine and methamphetamine are rising sharply. We will need far more than a prescribing database to guide policy moving forward.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

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

Marijuana Use May Affect Patient Anesthesia

By Kata Ruder, Kaiser Health News

When Colorado legalized marijuana, it became a pioneer in creating new policies to deal with the drug.

Now the state’s surgeons, nurses and anesthesiologists are becoming pioneers of a different sort in understanding what weed may do to patients who go under the knife.

Their observations and initial research show that marijuana use may affect patients’ responses to anesthesia on the operating table — and, depending on the patient’s history of using the drug, either help or hinder their symptoms afterward in the recovery room.

Colorado makes for an interesting laboratory. Since the state legalized marijuana for medicine in 2000 and allowed for its recreational sale in 2014, more Coloradans are using it — and they may also be more willing to tell their doctors about it.

Roughly 17% of Coloradans said they used marijuana in the previous 30 days in 2017, according to the National Survey on Drug Use and Health, more than double the 8% who reported doing so in 2006. By comparison, just 9% of U.S. residents said they used marijuana in 2017.

“It has been destigmatized here in Colorado,” said Dr. Andrew Monte, an associate professor of emergency medicine and medical toxicology at the University of Colorado School of Medicine and UCHealth. “We’re ahead of the game in terms of our ability to talk to patients about it. We’re also ahead of the game in identifying complications associated with use.”

One small study of Colorado patients published in May found marijuana users required more than triple the amount of one common sedation medicine, propofol, as did nonusers.

Those findings and anecdotal reports are prompting additional questions from the study’s author, Dr. Mark Twardowski, and others in the state’s medical field: If pot users indeed need more anesthesia, are there increased risks for breathing problems during minor procedures?

Are there higher costs with the use of more medication, if a second or third bottle of anesthesia must be routinely opened? And what does regular cannabis use mean for recovery post-surgery?

But much is still unknown about marijuana’s impact on patients because it remains illegal on the federal level, making studies difficult to fund or undertake.

It’s even difficult to quantify how many of the estimated 800,000 to 1 million anesthesia procedures that are performed in Colorado each year involve marijuana users, according to Dr. Joy Hawkins, a professor of anesthesiology at the University of Colorado School of Medicine and president of the Colorado Society of Anesthesiologists. The Colorado Hospital Association said it doesn’t track anesthesia needs or costs specific to marijuana users.

As more states legalize cannabis to varying degrees, discussions about the drug are happening elsewhere, too. On a national level, the American Association of Nurse Anesthetists recently updated its clinical guidelines to highlight potential risks for and needs of marijuana users. American Society of Anesthesiologists spokeswoman Theresa Hill said that the use of marijuana in managing pain is a topic under discussion but that more research is needed. This year, it endorsed a federal bill calling for fewer regulatory barriers on marijuana research.

Should Patients Disclose Marijuana Use? 

No matter where patients live, though, many nurses and doctors from around the country agree: Patients should disclose marijuana use before any surgery or procedure. Linda Stone, a certified registered nurse anesthetist in Raleigh, N.C., acknowledged that patients in states where marijuana is illegal might be more hesitant.

“We really don’t want patients to feel like there’s stigma. They really do need to divulge that information,” Stone said. “We are just trying to make sure that we provide the safest care.”

In Colorado, Hawkins said, anesthesiologists have noticed that patients who use marijuana are more tolerant of some common anesthesia drugs, such as propofol, which helps people fall asleep during general anesthesia or stay relaxed during conscious “twilight” sedation. But higher doses can increase potentially serious side effects such as low blood pressure and depressed heart function.

Limited airway flow is another issue for people who smoke marijuana. “It acts very much like cigarettes, so it makes your airway irritated,” she said.

To be sure, anesthesia must be adjusted to accommodate patients of all sorts, apart from cannabis use. Anesthesiologists are prepared to adapt and make procedures safe for all patients, Hawkins said. And in some emergency surgeries, patients might not be in a position to disclose their cannabis use ahead of time.

Even when they do, a big challenge for medical professionals is gauging the amounts of marijuana consumed, as the potency varies widely from one joint to the next or when ingested through marijuana edibles. And levels of THC, the chemical with psychoactive effects in marijuana, have been increasing in the past few decades.

“For marijuana, it’s a bit of the Wild West,” Hawkins said. “We just don’t know what’s in these products that they’re using.”

Marijuana’s Effects On Pain After Surgery

Colorado health providers are also observing how marijuana changes patients’ symptoms after they leave the operating suite — particularly relevant amid the ongoing opioid epidemic.

“We’ve been hearing reports about patients using cannabis, instead of opioids, to treat their postoperative pain,” said Dr. Mark Steven Wallace, chair of the pain medicine division in the anesthesiology department at the University of California-San Diego, in a state that also has legalized marijuana. “I have a lot of patients who say they prefer it.”

Matthew Sheahan, 25, of Denver, said he used marijuana to relieve pain after the removal of his wisdom teeth four years ago. After surgery, he smoked marijuana rather than using the ibuprofen prescribed but didn’t disclose this to his doctor because pot was illegal in Ohio, where he had the procedure. He said his doctor told him his swelling was greatly reduced. “I didn’t experience the pain that I thought I would,” Sheahan said.

In a study underway, Wallace is working with patients who’ve recently had surgery for joint replacement to see whether marijuana can be used to treat pain and reduce the need for opioids.

But this may be a Catch-22 for regular marijuana users. They reported feeling greater pain and consumed more opioids in the hospital after vehicle crash injuries compared with nonusers, according to a study published last year in the journal Patient Safety in Surgery.

“The hypothesis is that chronic marijuana users develop a tolerance to pain medications, and since they do not receive marijuana while in the hospital, they require a higher replacement dose of opioids,” said Dr. David Bar-Or, who directs trauma research at Swedish Medical Center in Englewood, Colo., and several other hospitals in Colorado, Texas, Missouri and Kansas. He is studying a synthetic form of THC called dronabinol as a potential substitute for opioids in the hospital.

Again, much more research is needed.

“We know very little about marijuana because we’ve not been allowed to study it in the way we study any other drug,” Hawkins said. “We’re all wishing we had a little more data to rely on.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Feds Warn of Counterfeit Oxycodone Deaths

By Pat Anson, PNN Editor

In the wake of four fentanyl overdoses in southern California, federal authorities have issued a public safety alert warning drug users about a lethal strain of counterfeit medication designed to look like 30mg oxycodone tablets.

The blue bills have the letter “M” in a box on one side and the number “30” with a line down the center on the other. On the street they are referred to as blues, M-30s or Mexican Oxy.

The pills were found at the scene of four fatal overdoses in San Diego County last week. The deaths in Poway, Santee, Lakeside and Valley Center were all reported within 24 hours.

Although tests on the pills are ongoing, authorities suspect they are laced with illicit fentanyl or carfentanil, which can be fatal in tiny doses.

SAN DIEGO SHERIFF’S DEPT. IMAGE

“That heroin, that meth, that coke, that oxy you think you are taking? Well, it just might have fentanyl in it, and it just might be the last thing you ever do,” U.S. Attorney Robert Brewer said in a statement. “I cannot be more clear than this: Fentanyl may be the costliest drug you ever do, because you may pay with your life, and you won’t even know you took it.”

Brewer said border seizures, prosecutions and overdoses are on pace to hit all-time highs in San Diego County by the end of 2019. The Medical Examiner’s Office has confirmed 50 fentanyl-related overdose deaths so far this year, plus another 28 suspected but yet-to-be confirmed cases.

If the trend continues, the death toll could potentially reach 130, which would amount to a 47 percent increase over last year’s total of 90 deaths. The victims are overwhelmingly male, with the average age about 36.

“Just when we think it can’t get any worse, the latest numbers prove us wrong,” Brewer said.  “I am alarmed by the dramatic surge in trafficking activity and deaths, particularly of young people. San Diego is the fentanyl gateway to the rest of the country, and we are working hard to close that gate with interdiction, prosecution and education.”

Federal authorities have confiscated 1,175 pounds of illicit fentanyl – more than half a ton -- at or near the international border so far this year. In addition, there has been a record number of seizures involving counterfeit blue pills labeled M-30 that contain fentanyl. The pills sell on the street for $9 to $30 each and are appearing around the country.

Ports of entry near San Diego are major transit points for illicit fentanyl smuggled in from Mexico. The fentanyl is usually transported in vehicles, often by legal U.S. residents acting as couriers.

A recent report from the Wilson Center found that Mexican cartels are playing an increased role in the fentanyl trade.

“San Diego is the fentanyl gateway to the rest of the country.”

— U.S. Attorney Robert Brewer

“Chinese companies produce the vast majority of fentanyl, fentanyl analogues, and fentanyl precursors, but Mexico is becoming a major transit and production point for the drug and its analogues as well, and Mexican traffickers appear to be playing a role in its distribution in the United States,” the report found.

“Both large and small organizations appear to be taking advantage of the surge in popularity of the drug, which is increasingly laced into other substances such as cocaine, methamphetamine, and marijuana—very often without the end-user knowing it. To be sure, rising seizures of counterfeit oxycodone pills laced with fentanyl illustrate that the market is maturing in other ways as well.”

Last week a former Mexican police officer was indicted for fentanyl trafficking by a federal grand jury in Texas. Assmir Contreras-Martinez, 30, was pulled over by a Texas trooper on Interstate 40 in Amarillo in May. About 73 pounds of illicit fentanyl powder was found inside his 2007 Ford Explorer, enough to kill 10 million people, according to DEA experts. 

Contreras-Martinez admitted he was paid $6,000 to transport the fentanyl from California to Florida and that it was his second such trip. Before his unlawful immigration to the United States nine months ago, Contreras-Martinez had been employed for eight years as a municipal police officer in Cananea, Sonora, Mexico.

‘Opioid of the Future’ Postponed

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is tapping the brakes on NKTR-181, an experimental opioid pain medication that has less abuse potential than traditional opioids like oxycodone or hydrocodone.

In an SEC filing, Nektar Therapeutics said it received a letter from the FDA on July 23 saying the agency was postponing all advisory committee meetings for opioid analgesics, including one scheduled for August 21 to discus Nektar’s new drug application for NKTR-181.

The FDA was due to make a final decision on NKTR-181 eight days later, but that too is apparently being postponed while the agency considers “a number of scientific and policy issues relating to this class of drugs.”

Nektar called NKTR-181 the “opioid of the future” because it is the first full mu-opioid agonist that can provide pain relief without the euphoria or “high” that can lead to abuse and addiction.

The molecular structure of NKTR-181 is designed to have low permeability across the blood-brain barrier, which slows its rate of entry into the brain.

In a Phase III clinical study, patients with chronic back pain reported that their pain scores dropped an average of 65% when taking NKTR-181 twice daily. Safety studies also found that recreational drug users had significantly less “drug liking” of NKTR-181 when compared to oxycodone.

NEKTAR IMAGE

The research was so promising the FDA gave NKTR-181 “fast track” designation to speed its development. Nektar executives told PNN two years ago they were hopeful the drug would be approved in late 2018, with a commercial launch early this year.

Obviously that didn’t happen. And the FDA’s fast track has turned into a slow walk.

Two FDA advisory committees met last month and decided “much better-quality data” was needed before approving any new opioids — even ones with low risk of abuse.  

The agency has been under growing public and political pressure to tighten its regulation of opioids. In February, a 60 Minutes report claimed the FDA “opened the floodgates” to the opioid epidemic by approving the use of OxyContin for chronic pain. The following month, the agency received a petition from Public Citizen calling for a moratorium on new opioid approvals because the agency “can no longer be trusted” due to its “poor record” of regulating opioids.

On July 25, Howard Robin, Nektar’s President and CEO, sold 100,000 shares of Nektar for $3.1 million. A spokesman said the sale was previously scheduled due to expiring options. The company’s chief financial officer and a director also sold shares this month. Nektar shares (NASDAQ: NKTR) lost about 10% of their value after the SEC filing was made public.

Lawyer Calls for DOJ to End ‘Indiscriminate Raids’ on Doctors

By Pat Anson, PNN Editor

In recent years, hundreds of physicians, pharmacists and addiction treatment doctors have had their offices raided and searched by DEA agents.

Many of the raids were orchestrated by the Justice Department’s Opioid Fraud and Abuse Detection Unit, a special team of investigators created in 2017 to mine opioid prescribing data to identify suspicious orders and practices. The investigations have resulted in the high-profile arrests of healthcare providers for fraud and risky opioid prescribing.

"If you're a doctor and you want to act like a drug dealer, we're going to treat you like one. And sometimes the only difference between a doctor and a drug dealer is a white coat," U.S. Attorney Jay Town said about a federal takedown in April that resulted in charges against 60 practitioners in seven states.

Rarely publicized are the cases where criminal charges are never filed because the evidence against doctors is weak or non-existent.

“It’s quite frustrating to see how their careers were ruined even though they never faced criminal charges. That’s because the government was incapable of bringing credible charges against them,” says attorney Michael Barnes, who is managing partner at DCBA Law & Policy, a law firm that advises healthcare providers. “When I read a criminal complaint, what I would see as ‘best practices’ is construed as criminal exploitative behavior on the part of the prosecutors.

“There’s a heavy bias against medications to treat pain and opioid use disorder that is driving some of the aggressive enforcement actions. Also, an overzealousness combined with a lack of understanding of the practice of medicine.”

Barnes recently wrote an op/ed, published online by American University’s Washington College of Law, calling for an end to the DOJ’s “indiscriminate raids” on doctors.

“DOJ raids and searches of professionals’ homes and medical clinics interrupt the delivery of health care, put patients’ lives at risk, and unjustly destroy careers and livelihoods. They also create confusion and fear,” wrote Barnes. “Not all health care professionals subject to the DOJ’s searches and seizures are ‘dirty docs.’ In fact, some of them are nationally recognized leaders not just in pain management, but also in addiction medicine.” 

Barnes cites the case of Dr. Stuart Gitlow, an addiction psychiatrist whose Rhode Island home and office were raided by FBI agents in March 2018. Sixteen months later, the reasons for the raid remain unclear and Gitlow, the former president of the American Society of Addiction Medicine, has not been charged with a crime.  

MICHAEL BARNES

Neither has Dr. Forest Tennant. In November 2017, DEA agents raided the office and home of Tennant, a prominent California pain physician who was flagged for “very suspicious prescribing patterns.” In a search warrant, the 76-year old Tennant was depicted as the kingpin of a drug trafficking organization that spanned several states.

“I know based on my training and experience that patients traveling long distances to obtain controlled substance prescriptions is another ‘red flag’ of drug abuse and addiction,” wrote DEA investigator Stephanie Kolb, who led a two-year investigation of Tennant.

But Kolb, who was self-employed as a dog walker and pet groomer before she started working for the DEA in 2012, failed to note that Tennant only treated intractable pain patients, many from out-of-state, and often prescribed high doses of opioids because of their chronically poor health. Some patients were in palliative care and near death, and one committed suicide after learning of the raid, fearing she would lose access to opioid medication.

Tennant denies any wrongdoing and was never formally charged, but retired from clinical practice a few months after the raid.

“It’s hard to continue operating when they never closed my case, and so I’m going to retire and move on,” Tennant told PNN at the time. “That’s on the advice of both my lawyers and my doctors."

(Dr. Tennant and the Tennant Foundation have given financial support to Pain News Network and are currently sponsoring PNN’s Patient Resources section.)  

Biased Investigations

Barnes says the biases of some prosecutors extends to the expert witnesses they hire to help build their cases. The role of these witnesses is important because they help DOJ persuade judges to sign off on search warrants that are key to gathering evidence. It’s a lucrative sideline for some paid witnesses, who charge the government hundreds of dollars an hour for their time and expertise.

“Expert witnesses are eager to give DOJ business to get the expert witness fees, and they of course will help to spin the facts in a way that is prejudicial to the defendant,” Barnes said. “What we’re seeing here is people who are really not qualified to be making assessments of other practices serving as experts for the government.” 

Dr. Timothy Munzing, a Kaiser Permanente family practice physician in California, has worked as a medical consultant for the DEA, FBI and DOJ on over 100 investigations, most of which involve prescriptions for opioids and other controlled substances.

According to GovTribe.com, which tracks payments to federal contractors, Munzing has been awarded nearly $1 million in DOJ contracts since 2017 and is currently working on nearly two dozen DEA investigations, mostly reviewing patient files and data from prescription drug monitoring programs.

It would be unusual for a family practice physician to treat an intractable pain patient without making a referral to a pain or palliative care specialist. But Munzing was one of the expert witnesses hired by the DEA to analyze Tennant’s prescribing.

“I find to a high level of certainty that after review of the medical records… that Dr. Tennant failed to meet the requirements in prescribing these dangerous medications,” Munzing wrote in an affidavit. “These prescribing patterns are highly suspicious for medication abuse/and or diversion. If the patients are actually using all the medications prescribed, they are at high risk for addiction, overdose, and death.”  

Munzing’s affidavit and the DEA search warrant identified no patients who were actually harmed while under Tennant’s care. As PNN reported, some patients found the allegation that they were selling their medication and funneling the profits back to Tennant laughable.      

“It’s like everything else they do. They don’t talk to any patients. They don’t talk to any doctors. They just go and throw all this stuff out there and making all these incriminations against people. They don’t have any evidence that I’ve sold anything. It’s just ludicrous,” said Ryle Holder, a Tennant patient who lives in Georgia.  

Barnes says the bias against opioid prescribing “is inherent in the work of many of the investigators and prosecutors.”

“Then there is the incompetence as it relates to many of the law enforcement officers not having the medical expertise to make judgements of a medical nature. And then, when they do consult with the experts, those experts are typically trying to please their clients and getting repeat business as a result,” he told PNN. 

State Medical Boards

To bring more expertise into investigations of healthcare providers, Barnes is proposing that state medical boards play a more prominent role. He wants Congress to amend federal law to require DOJ investigators and prosecutors to get a referral from a state licensing board before investigating a practitioner for misconduct. Similar laws at the state level would also need to be changed to require state and local law enforcement to get a referral from a medical licensing board.

To make sure complaints are handled in a timely manner, Barnes says federal funds should be used to bolster the budgets of state licensing boards so they can investigate allegations of misconduct.  

“There are some detractors who say medical boards didn’t do an adequate job leading up to the overdose crisis. But the reality is neither did law enforcement,” Barnes says. “The medical boards could get up to speed and make these assessments on medical needs and patient care to make sure that healthcare providers can be assessed with medical expertise, rather than law enforcement trying to guess about standard of care and best practices.”

“Making it more difficult for law enforcement to investigate potential diversion of dangerous and addictive controlled substances, including powerful painkillers, is probably not going to happen right now,” says DEA spokesman Rusty Payne.

“This idea that people need to worry about the DEA hiding in the bushes if they write an oxycodone prescription is ridiculous.”

— Rusty Payne, DEA spokesman

Payne points out the DEA is both a law enforcement and regulatory agency, one that oversees 1.3 million practitioners licensed to prescribe controlled substances. He says enforcement actions are relatively rare and not “indiscriminate” as Barnes suggests.

“The numbers are incredibly low. It is a very, very, very small number.  So this idea that people need to worry about the DEA hiding in the bushes if they write an oxycodone prescription is ridiculous,” he told PNN. “We don’t have the resources. We don’t track individual prescriptions. We look for patterns and large-scale significant diversion.”  

Getting state medical boards involved, according to Payne, is not a good idea.

“I don’t think making it harder for us to scrutinize those that are acting outside the law is in anyone’s best interest,” he said.

But Barnes’ proposal makes sense, according to Dr. Lynn Webster, a PNN columnist and former president of the American Academy of Pain Medicine. 

“Barnes makes a sensible recommendation. If the law enforcement suspects a provider is not complying with the law, then the first step should be a referral to the medical board where the provider can be evaluated by their peers,” Webster said. “If a doctor goes to trial, they will not be evaluated by their peers. That is not the way the justice system is supposed to work.” 

Webster was once the target of a federal investigation of his opioid prescribing practices and DEA agents raided his Utah pain clinic in 2010. Four years later, the DOJ said it would not prosecute Webster, who said his “reputation was tarnished forever.”  

“DEA investigations are often designed to entrap a provider on technicalities.  Even if an investigation never leads to any charges the doctor's reputation is damaged.  In the court of public opinion an investigation must mean something was wrong,” Webster said. 

Feds Found ‘Staggering’ Drug Testing Fraud at Tennessee Pain Clinics

By Fred Schulte, Kaiser Health News

The Justice Department has accused a defunct chain of Tennessee-based pain clinics of cheating Medicare and other taxpayer-funded health insurers out of at least $25 million in needless urine drug tests and genetic testing.

The civil lawsuit names Comprehensive Pain Specialists, also known as Anesthesia Services Associates PLLC; four of its physician owners; and a former top executive. The doctors include Tennessee Republican State Sen. Steven Dickerson and Peter Kroll, both anesthesiologists.

At its peak, CPS ran 60 pain clinics in a dozen states and treated some 48,000 patients per month, according to the suit. It shut down abruptly last summer, leaving many chronic pain patients scrambling to find a new source of narcotic medicines.

The Justice Department fraud case centers largely on the company’s lucrative urine-testing lab in Brentwood, Tenn., which CPS financed with a $1.5 million loan. The suit also alleges overbilling from acupuncture and other services offered to patients.

CPS was the subject of a November 2017 investigation by Kaiser Health News that scrutinized Medicare billings for urine drug tests.

Medicare and other federal programs paid over $70 million from 2011 to 2018 for CPS-ordered urine tests, an amount the lawsuit called “staggering.” TennCare, the state’s Medicaid program, paid more than $9 million more during that time.

“For this reason, CPS considered [urine tests] to be ‘liquid gold’ — with revenues of tens of millions of dollars for what was largely unnecessary medical testing,” according to the suit.

The chain’s owners and then-CEO John Davis “viewed every CPS patient as an opportunity to make money, without regard to the individualized need for treatment,” the suit alleges. Davis was convicted last year in Nashville on federal criminal health care fraud charges. He has since filed a motion for a new trial.

Dan Martin, an attorney representing Kroll, said in an emailed statement: “We are aware of the allegations and very familiar with the actual facts. Dr. Kroll did not engage in any wrongdoing whatsoever, and we look forward to correcting the government’s misunderstanding of the facts.”

Dickerson’s attorney, Ed Yarbrough, also issued a statement that read: “Dr. Dickerson is an honest man. We will prove that in court.” 

$8.5 Billion Annually Spent on Drug Tests

In its investigation, KHN, with assistance from researchers at the Mayo Clinic, found that spending on urine screens and related genetic tests quadrupled from 2011 to 2014 to an estimated $8.5 billion a year — more than the entire budget of the Environmental Protection Agency. The federal government paid medical providers more to conduct urine drug tests in 2014 than it spent on the four most recommended cancer screenings combined.

CPS was among the nation’s most aggressive testers. KHN found that in 2014 five of its medical professionals stood among the nation’s top billers. Anita Bayles, a nurse practitioner working at a CPS clinic in Cleveland, Tenn., generated $1.1 million in urine-test billings that year, according to Medicare records analyzed by KHN.

The Justice Department suit says that CPS believed Bayles ordered too many urine tests and overprescribed opioids and in September 2016 decided to fire her. But the decision was reversed by CEO Davis “because of her ability to generate revenues,” according to the suit. Bayles could not be reached for comment.

IMAGE COURTESY OF MARK COLLEN AND PAIN EXHIBIT

Though CPS ran six or more urine tests a year on many patients receiving narcotics, its doctors often did not review the results to make sure patients did not abuse them, according to the suit.

Kroll, who also served as CPS’ medical director, told KHN in 2017 that the high volume of tests was justified to keep patients safe and to reduce chances of black market sales of pills.

Kroll billed Medicare $1.8 million for urine tests in 2015, the KHN analysis of Medicare billing records found.

Kroll said in a 2017 interview that he and Dickerson came up with the idea to open a high-quality pain practice over a cup of coffee at a Nashville Starbucks in 2005.

But the Justice Department alleges that CPS expanded rapidly through bilking the government, conduct that its top executives and founders “failed to take any action to stop,” according to the suit.

In what is called a “particularly egregious example of this fraudulent conduct,” the Justice Department alleged that Kroll caused over 2,500 claims to be submitted to Medicare, for which CPS was paid almost $350,000, during a 10-day period in May 2017 when Kroll was on vacation in Italy.

“Because of these fraudulent claims, Kroll’s billing privileges with Medicare have been revoked,” according to the suit.

The lawsuit states that Medicare officials began investigating overcharging for urine testing at CPS in 2014 and eventually directed the company to repay the government $27.4 million in an extrapolated penalty. But CPS aggressively appealed the decision and managed to get it overturned and stay in business.

Once among the largest pain management groups in the Southeast, CPS crumbled amid financial woes that included nearly a dozen civil suits alleging unpaid debts, as well as the criminal case against Davis. In a court filing in December, the company said that it had terminated all of its employees and that its debts “greatly exceed its assets.”

In total, Medicare paid CPS over $150 million from 2011 to 2018, a large part of which was related to urine testing, while TennCare paid CPS over $32.5 million, according to the suit.

The Justice Department complaint consolidates several whistleblower cases filed against the company by doctors and other former employees. Federal whistleblower cases seek recovery of money paid improperly and can include treble damages, or three times the amount of the original overpayment.

One of the whistleblowers said he toured the lab with CPS executives and observed an “overpowering and unpleasant smell of urine.” In response, a CPS executive said, “To me, it smells like money,” according to the whistleblower’s suit.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Teens Who Abuse Rx Opioids More Likely to Try Heroin

By Roger Chriss, PNN Columnist

A new study from the University of Southern California finds that teens who abuse prescription opioids are more likely to start using heroin by high school graduation.  

Published in JAMA Pediatrics, the study tracked nearly 3,300 students in ten public high schools in the Los Angeles area from 2013-2017. Nearly 600 of those students reported using prescription opioids to get high.

By the end of high school, a total of 70 students had started using heroin, including about 12% of those who abused opioid medication. Only 1.7% of students who did not misuse prescription opioids tried heroin.

The researchers looked closely at not only the nonmedical use of prescription opioids, but also the use of other substances. A family history of smoking, alcohol and drug problems, and interpersonal factors such as impulsiveness, anxiety, depression and delinquent behavior were also assessed.

Among all the different factors, the best predictor of heroin use was the abuse of prescription opioids. This tendency was significantly stronger than the use of alcohol, cannabis, cigarettes or other non-opioid drugs.

"Prescription opioids and heroin activate the brain's pleasure circuit in similar ways," said senior author Adam Leventhal, PhD, director of the USC Institute for Addiction Science. "Teens who enjoy the 'high' from prescription opioids could be more inclined to seek out other drugs that produce euphoria, including heroin.”

Researchers also found that students who initiated heroin use were more likely to be male, have less parental monitoring, more delinquent behavior, and impulsive personalities.

The USC study adds to previous research on the complex drug use trajectories that culminate with heroin. It has long been known that nonmedical prescription opioid use is associated with later heroin use, with some anti-opioid activists claiming that 80% of heroin addicts begin by abusing prescription opioids. That is a misleading statistic, as I discussed in a previous column.

There clearly is an association between the misuse of prescription opioids and heroin use, but as the USC researchers found, many other factors are also involved and more research is needed. Their study, for example, did not look at how teens who misused prescription opioids obtained them.  Most likely, they were obtained from friends or family members.

The USC study findings not only advance our understanding of heroin initiation, but also signal the importance of developing better policies to prevent nonmedical opioid use.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

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

FDA Approves First Generics for Lyrica

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has approved the first generic versions of Lyrica (pregabalin), a medication widely prescribed for the treatment of fibromyalgia, diabetic neuropathy and other types of chronic pain.

Lyrica has been a blockbuster drug for Pfizer since its approval in 2004, generating revenue of $4.6 billion annually. The recent expiration of Pfizer’s patent on Lyrica opened the door to much cheaper generic competitors.

A one year supply of Lyrica currently costs about $2,800 in the United States, according to Healthcare Bluebook, while a similar dose of pregabalin under the UK’s National Health Service costs about $74.

“Today’s approval of the first generics for pregabalin, a widely-used medication, is another example of the FDA’s longstanding commitment to advance patient access to lower cost, high-quality generic medicines,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.

“The FDA requires that generic drugs meet rigorous scientific and quality standards. Efficiently bringing safe and effective generics to market so patients have more options to treat their conditions is a top priority for the FDA.”

The FDA granted approvals for generic pregabalin to 9 drug makers: Alembic Pharmaceuticals, Alkem Laboratories, Amneal Pharmaceuticals, Dr. Reddy’s Laboratories, InvaGen Pharmaceuticals, MSN Laboratories, Rising Pharmaceuticals, Sciegen Pharmaceuticals, and Teva Pharmaceuticals.

Pfizer’s patent for Lyrica CR — an extended released version of Lyrica — remains in effect until April, 2021.

Side Effects

The most common side effects for Lyrica are dizziness, somnolence, dry mouth, swelling, blurred vision, weight gain and difficulty concentrating. Lyrica’s warning label also cautions users that the drug may cause suicidal thoughts in about 1 in 500 people.

Pregabalin is classified as Schedule V controlled substance in the U.S., which means it has a low potential for abuse. In recent years, however, there is growing concern that pregabalin and its sister drug gabapentin (Neurontin) are being abused and overprescribed. The drugs were recently classified as controlled substances in the UK.

Pregabalin and gabapentin were originally developed to prevent epileptic seizures, but their use has tripled over the past 15 years as more doctors prescribed them off-label as “safer” alternatives to opioids.

A recent study in the British Medical Journal found the drugs increase the risk of suicide, overdose and traffic accidents in younger people. The risks were strongest for those taking pregabalin and were most pronounced among adolescents and young adults aged 15 to 24. Patients aged 55 and older taking gabapentinoids were not at greater risk.

Pharmacists and Rx Wholesalers Charged with Drug Trafficking

By Pat Anson, PNN Editor

Major pharmaceutical companies like Purdue Pharma, Mallinckrodt and Johnson & Johnson are often singled out for their role in the nation’s opioid crisis. But wholesalers, pharmacies and other parts of the drug distribution system are also coming under scrutiny.

This week the former president and former compliance officer for an Ohio drug distributor and two West Virginia pharmacists were arrested after being indicted for conspiring to distribute controlled substances.

The company, Miami-Luken, supplied drugs to over 200 pharmacies in Ohio, West Virginia, Indiana and Tennessee, generating over $173 million in sales annually.

Prosecutors say Miami-Luken distributed opioid pain medication “outside the scope of professional practice and not for a legitimate medical purpose.”

Between 2011 and 2015, the company allegedly ignored “obvious signs of abuse” by distributing more than 2.3 million oxycodone pills and 2.6 million hydrocodone pills to a pharmacy in Oceana, West Virginia, a town of less than 1,400 people.

From 2008 to 2011, over 3.7 million hydrocodone pills were supplied by Miami-Luken to a pharmacy in Kermit, West Virginia, which has about 400 people.

Criminal Charges Rare

According to CNN, it’s only the second time a drug distributor has been criminally charged with illegally distributing opioid painkillers. In April, two former executives of the Rochester Drug Co-Operative in upstate New York were charged with drug trafficking for failing the stop suspicious orders for opioids.

In previous cases, wholesalers, pharmacies and even hospitals paid heavy fines for not being alert to suspicious activity. Last year, for example, Effingham Health System of Georgia agreed to pay a $4.1 million settlement after the DEA uncovered the diversion of tens of thousands of oxycodone tablets from its hospital.

In 2017, CVS Health agreed to pay a $5 million fine to settle allegations that several CVS pharmacies in California failed to detect thefts of hydrocodone. In 2015, CVS paid a $22 million fine because two of its Florida pharmacies filled bogus prescriptions for opioids.  

Cardinal Health, one of the nation’s largest drug wholesalers, was fined $34 million by the DEA in 2012 after it failed to report suspicious orders for hydrocodone at a Florida distribution facility.

The list goes on and on. The point is that no one went to prison or was criminally charged in any of these cases. Which may be about to change. The four defendants in the Miami-Luken case face up to 20 years in prison. 

“Today’s arrests should be a wakeup call to distributors and pharmacists who are allowing opioid prescription pills to be illegally sold and dispensed from their facilities,” said DEA Assistant Administrator John Martin. “These actions will not be tolerated by the DEA, and they will be brought to justice.”

Patients Caught in the Middle

Big fines and prison terms may be appropriate, but not if they result in legitimate patients with legitimate prescriptions being denied access to opioids.  That’s what happened in April to a California woman with Stage 4 terminal breast cancer, who couldn’t get a prescription filled for Norco at her local Rite Aid pharmacy.  

April Doyle’s tearful, 6-minute video about her experience went viral online, and she wound up getting apologies from a Rite Aid vice-president, the store manager and even the pharmacist who sent her away without pain medication.

Rite-Aid’s caution in filling opioid prescriptions may have stemmed from being added a few months earlier as a defendant in New York City’s opioid lawsuit (along with CVS, Walgreens and Walmart) by the law firm of Simmons Hanly Conroy.  

“Many plaintiffs in opioid lawsuits are amending their complaints to include these retailers because they failed to monitor the drugs sold out of their pharmacy windows,” Simmons Hanly said in a statement.

The Washington Post released a report this week on how drug companies, wholesalers and pharmacies “saturated the country” with 76 billion oxycodone and hydrocodone pills from 2006 through 2012. Those pills, according to the Post, “fueled the prescription opioid epidemic” and resulted in nearly 100,000 deaths.

But as Jeffrey Singer points out in Cato at Liberty, the Post is contributing to a false narrative about the opioid crisis by pinning the blame on prescription opioids, while largely ignoring the fact that most deaths are caused by illicit drugs such as heroin and illicit fentanyl.

“The overdose problem has never been a product of doctors treating patients for pain. It has always been a product of (a growing population of) nonmedical users accessing drugs in a dangerous black market fueled by drug prohibition,” Singer wrote.  “The continued obsession about the number of pain pills being prescribed causes patients to go undertreated for their pain and will not make one IV drug user pull the needle out of their arm.”

Closing Arguments in Oklahoma Opioid Trial

By Jackie Fortier, StateImpact Oklahoma

A global megacorporation best known for Band-Aids and baby powder may have to pay billions for its alleged role in the opioid crisis. Johnson & Johnson was the sole defendant in a closely watched trial that wrapped up in Oklahoma state court this week, with a decision expected later this summer.

The ruling in the civil case could be the first that would hold a pharmaceutical company responsible for one of the worst drug epidemics in American history.

Oklahoma Attorney General Mike Hunter’s lawsuit alleges Johnson & Johnson and its subsidiary Janssen Pharmaceuticals helped ignite the opioid crisis with overly aggressive marketing, leading to thousands of overdose deaths over the past decade in Oklahoma alone.

The trial took place over seven weeks in the college town of Norman. Instead of a jury, a state judge heard the case. During closing arguments Monday, Hunter called the company the “kingpin” of the opioid crisis.

“What is truly unprecedented here is the conduct of these defendants on embarking on a cunning, cynical and deceitful scheme to create the need for opioids,” Hunter said.

The state urged Judge Thad Balkman, who presided over the civil trial, to find Johnson & Johnson liable for creating a “public nuisance” and force the company to pay more than $17 billion over 30 years to abate the public health crisis in the state.

Driving the opioid crisis home has been a cornerstone of Oklahoma’s lawsuit. In closing arguments Monday, one of the state’s attorneys, Brad Beckworth, cited staggering prescribing statistics in the county where the trial took place.

“What we do have in Cleveland County is 135 prescription opioids for every adult,” Beckworth said. “Those didn’t get here from drug cartels. They got here from one cartel: the pharmaceutical industry cartel. And the kingpin of it all is Johnson & Johnson.”

Johnson & Johnson’s attorney Larry Ottaway, rejected that idea in his closing argument, saying the company’s products, which had included the fentanyl patch Duragesic and the opioid-based pill Nucynta, were minimally used in Oklahoma.

He scoffed at the idea that physicians in the state were convinced to unnecessarily prescribe opioids due to the company’s marketing tactics.

“The FDA label clearly set forth the risk of addiction, abuse and misuse that could lead to overdose and death. Don’t tell me that doctors weren’t aware of the risks,” Ottaway said.

Ottaway played video testimony from earlier in the trial, showing Oklahoma doctors who said they were not misled about the drugs’ risks before prescribing them.

“Only a company that believes its innocence would come in and defend itself against a state, but we take the challenge on because we believe we are right,” Ottaway argued.

Initially, Hunter’s lawsuit included Purdue Pharma, the maker of OxyContin. In March, Purdue Pharma settled with the state for $270 million. Soon after, Hunter dropped all but one of the civil claims, including fraud, against the two remaining defendants.

Just two days before the trial began, another defendant, Teva Pharmaceuticals of Jerusalem, announced an $85 million settlement with the state. The money will be used for litigation costs and an undisclosed amount will be allocated “to abate the opioid crisis in Oklahoma,” according to a press release from Hunter’s office.

Both companies deny any wrongdoing.

The Legal Liability of ‘Public Nuisance’

Most states and more than 1,600 local and tribal governments are suing drugmakers who manufactured various kinds of opioid medications, and drug distributors. They are trying to recoup billions of dollars spent addressing the human costs of opioid addiction.

“Everyone is looking to see what’s going to happen with this case, whether it is going to be tobacco all over again, or whether it’s going to go the way the litigation against the gun-makers went,” says University of Georgia law professor Elizabeth Burch.

But the legal strategy is complicated. Unlike the tobacco industry, from which states won a landmark settlement, the makers of prescription opioids manufacture a product that serves a legitimate medical purpose, and is prescribed by highly trained physicians — a point that Johnson & Johnson’s lawyers made numerous times during the trial.

Oklahoma’s legal team based its entire case on a claim of public nuisance, which refers to actions that harm members of the public, including injury to public health. Burch says each state has its own public nuisance statute, and Oklahoma’s is very broad.

“Johnson & Johnson, in some ways, is right to raise the question: If we’re going to apply public nuisance to us, under these circumstances, what are the limits?” Burch said. “If the judge or an appellate court sides with the state, they are going to have to write a very specific ruling on why public nuisance applies to this case.”

Burch said the challenge for Oklahoma has been to tie one opioid manufacturer to all of the harms caused by the ongoing public health crisis, which includes people struggling with addiction to prescription drugs, but also those harmed by illegal street opioids, such as heroin.

University of Kentucky law professor Richard Ausness agreed that it’s difficult to pin all the problems on just one company.

“Companies do unethical or immoral things all the time, but that doesn’t make it illegal,” Ausness said.

If the judge rules against Johnson & Johnson, Ausness said, it could compel other drug companies facing litigation to settle out of court. Conversely, a victory for the drug giant could embolden the industry in the other cases.

Oklahoma’s Paid Expert Witness

Earlier in the trial, the state’s paid expert witness, Dr. Andrew Kolodny, testified that Johnson & Johnson did more than push its own pills — until 2016, it also profited by manufacturing raw ingredients for opioids and then selling them to other companies, including Purdue, which makes Oxycontin.

“Purdue Pharma and the Sacklers have been stealing the spotlight, but Johnson & Johnson in some ways, has been even worse,” said Kolodny, who indicated he would be paid upwards of $500,000 for his testimony.

Kolodny said that’s why the company downplayed to doctors the risks of opioids as a general class of drugs, knowing that almost any opioid prescription would benefit its bottom line.

The state’s case also focused on the role of drug sales representatives. Drue Diesselhorst was one of Johnson & Johnson’s busiest drug reps in Oklahoma. Records discussed during the trial showed she continued to call on Oklahoma doctors who had been disciplined by the state for overprescribing opioids. She even continued to meet with doctors who had patients who died from overdoses.

DR. ANDREW KOLODNY

But Diesselhorst testified she didn’t know about the deaths, and no one ever instructed her to stop targeting those high-prescribing physicians.

“My job was to be a sales rep. My job was not to figure out the red flags,” she said on the witness stand.

Johnson & Johnson’s Defense

Throughout the trial, Johnson & Johnson’s defense team avoided many of the broader accusations made by the state, instead focusing on the question of whether the specific opioids manufactured by the company could have caused Oklahoma’s high rates of addiction and deaths from overdose.

Johnson & Johnson’s lawyer, Larry Ottaway, argued the company’s opioid products had a smaller market share in the state compared to other pharmaceutical companies, and he stressed that the company made every effort when the drugs were tested to prevent abuse.

He also pointed out that the sale of both the raw ingredients and prescription opioids themselves are heavily regulated.

“This is not a free market,” he said. “The supply is regulated by the government.”

Ottaway maintained the company was addressing the desperate medical need of people suffering from debilitating, chronic pain — using medicines regulated by the Food and Drug Administration and the Drug Enforcement Administration. Even Oklahoma purchases these drugs, for use in state health care services.

Judge Thad Balkman is expected to announce a verdict in August.

If the state’s claim prevails, Johnson & Johnson could, ultimately, have to spend billions of dollars in Oklahoma helping to ease the epidemic. State attorneys are asking that the company pay $17.5 billion over 30 years, to help abate the crisis in the state.

Balkman could choose to award the full amount, or just some portion of it, if he agrees with the state’s claim.

“You know, in some ways I think it’s the right strategy to go for the $17 billion,” Burch, the law professor, said. “[The state is saying] look, the statute doesn’t limit it for us, so we’re going to ask for everything we possibly can.”

In the case of a loss, Johnson & Johnson is widely expected to appeal the verdict. If Oklahoma loses, the state will appeal, Attorney General Mike Hunter said Monday.

This story is part of a partnership that includes StateImpact Oklahoma, NPR and Kaiser Health News. KHN is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

WHO Criticized for Withdrawing Opioid Guidelines

By Pat Anson, PNN Editor

A coalition of international palliative care organizations is protesting a decision by the World Health Organization (WHO) to withdraw two guidelines for treating pain with opioid pain medication.

“We are extremely concerned that the withdrawal of these guidance documents will lead to confusion and possible extreme measures that will hinder access to patients with legitimate medical needs,” the coalition said in a joint statement released this week.

The guidelines were withdrawn after two U.S. congressmen released a report that accused WHO of being “corruptly influenced” by Purdue Pharma and other opioid manufactures when it developed the guidelines in 2011 and 2012. The guidelines for treating pain in adults and children state that opioids “are known to be safe and there is no need to fear accidental death or dependence.”

Reps. Katherine Clark (D-MA) and Hal Rogers (R-KY) said the WHO guidelines served as “marketing materials” for Purdue, the maker of OxyContin.

“We are highly troubled that, after igniting the opioid epidemic that cost the United States 50,000 lives in 2017 alone… Purdue is deliberately using the same playbook on an international scale,” the report said. “If the recommendations in these WHO guidelines are followed, there is significant risk of sparking a worldwide public health crisis.”

WHO withdrew the guidelines a month after the report was released, citing “new scientific evidence” that emerged since their publication.

WHO’s decision to withdraw the guidelines gave credibility to a congressional report based largely on innuendo, according to the statement released by over a hundred palliative care organizations, including the American Academy of Hospice and Palliative Medicine and the UK-based International Observatory on End of Life Care.

“The report contains serious factual inaccuracies and draws inaccurate and unfair conclusions. It includes misleading information, and by making false accusations of existing collaborations and alliances to advance pain relief and palliative care, concludes that there was corruption within WHO,” the coalition said. “No staff member of the offices of the U.S. representatives contacted any of the organizations or individuals mentioned in the document to seek our responses to the allegations made in the report.”

According to the coalition, the withdrawal of the guidelines could further impede the availability of pain medication in third world countries, where less than 2% of palliative care patients have access to opioids.

“Under-treatment of severe pain is reported in more than 150 countries,” the coalition said. “At least 5 billion people live in countries affected by the crisis of under-consumption, and more than 18 million annually die with untreated, excruciating pain.”

The coalition cited the case of a cancer patient in New Delhi, India, who wanted to die until she was able to obtain opioids through a CanSupport palliative care program.  

“I am a functioning human being in charge of my life once again. This has been made possible thanks to the oral morphine that I now take.”

— Cancer patient in New Delhi, India

“I was a human wreck. My family was at their wits end as to how to help me. Because of my excruciating pain, I could not sit, sleep, eat or drink, let alone speak or think. When the team first met me my first request to them was for an injection that would put me out of my misery,” the patient said.

“Today, I am a functioning human being in charge of my life once again. This has been made possible thanks to the oral morphine that I now take on a regular basis.”

The palliative care coalition said it was unfair to deny opioids to patients in third world countries because of abuse and addiction problems in the U.S. and other developed nations.  The coalition called on WHO to update and revise the guidelines “with all deliberate speed” and to reinstate them until the revisions are made.