Feds Withdrew Request to Ban Kratom in 2018

By Pat Anson, PNN Editor

Federal health officials quietly withdrew their request for kratom to be classified as a Schedule I controlled substance in August 2018, according to a previously undisclosed letter to the U.S. Drug Enforcement Administration.

The letter from Brett Girior, MD, Assistant Secretary for Health & Human Services (HHS), to the DEA’s acting administrator cited concerns that “there is a significant risk of immediate adverse public health consequences to potentially millions of users if kratom or its components are included in Schedule I.”

Kratom is an herbal supplement comes from the leaves of a tree that grows in southeast Asia, where kratom has been used for centuries as a natural stimulant and pain reliever. In recent years, millions of Americans have discovered kratom, using it to self-treat their chronic pain, anxiety, depression and addiction. Classifying kratom’s two active ingredients, the alkaloids mitragynine and 7-hydroxymitragynine, as Schedule I substances would effectively ban kratom by making its sale and possession illegal.  

The 2018 letter from HHS was made public this week by the American Kratom Association (AKA), an advocacy group for kratom consumers and vendors, which said it obtained the letter from Rep. Mark Pocan (D-WI).

“The decision by the FDA to not disclose the recission of their recommendation for scheduling of kratom that took place more than 2 ½ years ago has significantly misled policy makers, the media, and kratom consumers in the belief a scheduling decision was imminent,” Mac Haddow, Senior Fellow on Public Policy for the AKA, said in a statement. “Six states were duped by this messaging to pass bans on kratom sales, and a number of local county and city governments also based their bans on the FDA’s claims.

“Through all of this the FDA has remained silent and has failed to disclose that HHS reviewed their scheduling recommendation and took the unprecedented action to rescind the recommendation because the FDA had failed to meet its burden under the CSA (Controlled Substance Act).”

An FDA spokesperson said it was not up the agency to disclose the letter’s existence.

“While the FDA is an agency within HHS, the letter at issue was not the FDA’s to publicly disclose and any announcement regarding a decision to schedule or not schedule a potential controlled substance is made by the Drug Enforcement Administration, not the FDA,” the spokesperson said in an email to PNN.

‘Lack of Evidence’ Kratom is Harmful

Girior’s letter to DEA said there was a “relative lack of evidence” that kratom can be abused and posed a public health threat.

“Although there remains cause for concern for 7-hydroxymitragynine and potentially mitragynine, the level of scientific data and analysis presented by the FDA and available in the literature do not meet the criteria for inclusion of kratom or its chemical components in Schedule I of the CSA at this time,” Girior wrote. 

“There is still debate among reputable scientists over whether kratom by itself is associated with fatal overdoses. Further analysis and public input regarding kratom and its chemical components are needed before any scheduling should be undertaken.”  

The DEA tried unsuccessfully to list kratom as a Schedule I substance in 2016, calling it an “imminent hazard to public safety,” a decision that was reversed after a public outcry from kratom supporters. 

But federal efforts to demonize kratom continue to this day, led for a time by FDA Commissioner Scott Gottlieb, who claimed kratom was an opioid and should not be used to treat any medical condition. Gottlieb resigned as FDA Commissioner in 2019, eight months after Girior’s letter. The agency he led remains opposed to kratom.   

“Kratom products have been associated with significant potential safety concerns. While it is important to gather more evidence, data suggest that certain substances in kratom have opioid properties that expose users to the risks of addiction, abuse and dependence,” the FDA spokesperson said.

“There is no FDA-approved drug containing, or derived from kratom, and the agency has received concerning reports about the safety of kratom. The FDA is actively evaluating available scientific information on this issue. In addition, FDA has sent numerous letters to firms that have marketed kratom products with unsubstantiated claims that their products can treat opioid withdrawal and addiction and other serious medical conditions.”

Kratom use has been growing in the U.S. as people seek alternatives to opioid pain relievers and other pharmaceutical drugs. Most kratom users say the leaves have a mild analgesic and stimulative effect, similar to coffee.  

A recent study funded by the National Institute on Drug Abuse concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and is “relatively safe” to use.

Feds Incinerate 28 Tons of Kratom

By Pat Anson, PNN

Over 28 tons of the herbal supplement kratom were recently destroyed by the federal government, the final chapter in a legal battle over one of the largest seizures of kratom in U.S. history.

The U.S. Marshals Office paid a hazardous waste company nearly $30,000 to transport the kratom from South Carolina to Florida, where it was incinerated at an energy-from-waste facility. The kratom had an estimated value of $1 million.

Kratom is a dietary supplement that millions of Americans use to self-treat their chronic pain, anxiety, depression and addiction.  It comes from the leaves of a tree that grows in southeast Asia, where kratom has been used for centuries as a natural stimulant and pain reliever.

The incinerated kratom was seized in 2018 after FDA inspectors found large quantities of kratom powder and capsules at a warehouse in Myrtle Beach, SC operated by Earth Kratom, a kratom wholesaler and vendor.

At the time, the federal government was engaged in a public relations campaign against kratom, led by then-FDA Commissioner Scott Gottlieb. Federal officials claimed kratom was a risky and addictive substance that should not be used to treat any medical condition.

“Serious concerns exist regarding the effect of kratom on multiple organ systems. Consumption of kratom can lead to a number of health impacts, including respiratory depression, vomiting, nervousness, weight loss, and constipation. Kratom consumption has been linked to neurologic, analgesic and sedative effects, addiction, and hepatic toxicity,” U.S. Attorneys said in a civil forfeiture complaint that led to the kratom being seized.

Kratom can be sold legally in South Carolina and most U.S. states, but vendors can run into trouble if they claim it can be used to treat medical conditions.

“There’s nothing wrong with our facilities or our product,” explained Brian Stall, supervising manager for Earth Kratom. “We were selling a product for human consumption and they didn’t like that.”

Stall told PNN that Earth Kratom’s lawyers were able to persuade a judge to order the kratom returned, but it was seized a second time by U.S. Marshals. The kratom was wrapped in plastic and remained at Earth Kratom’s warehouse, but was off-limits to the company.

“They took all of our product and half of our building at that point,” said Stall. “It was a tough time for us. We’d worked really hard and really believed in the product. It really sucked.”

Earth Kratom’s entire inventory may have gone up in smoke, but it survived the ordeal and remains in business. It sells one of the most popular kratom brands, Trainwreck Kratom, a blend that combines several different kratom strains. PNN’s Crystal Lindell raved about Trainwreck as a pain reliever in a 2018 column.

Scott Gottlieb resigned as FDA commissioner in March 2019 and weeks later joined the board of directors at Pfizer. Although the FDA’s campaign against kratom seems to have quieted since Gottlieb’s departure, an import alert remains in effect that allows FDA inspectors to seize kratom products even “without physical examination.”    

A recent study funded by the National Institute on Drug Abuse concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and has a low risk of adverse effects.

FDA Finds Unsafe Levels of Heavy Metals in Kratom

By Pat Anson, PNN Editor

The American Kratom Association’s new certified vendor program has gotten off to an inauspicious start. Kraken Kratom, the first vendor to qualify under the AKA’s Good Manufacturing Standards (GMP) program, has been flagged by the Food and Drug Administration for having dangerous levels of heavy metals in some of its products.

The FDA this week released the final test results on 30 kratom products found to contain levels of lead and nickel considered unsafe for daily human consumption. Five of the 30 samples that tested positive came from Kraken Kratom or one of its affiliated vendors.

“The analysis found significant levels of lead and nickel at concentrations that exceed safe exposure for oral daily drug intake,” the FDA said in a statement. “Based on these test results, the typical long-term kratom user could potentially develop heavy metal poisoning, which could include nervous system or kidney damage, anemia, high blood pressure, and/or increased risk of certain cancers.”

Ironically, last month Kraken Kraken became the first company to receive the AKA’s seal of approval as a certified GMP vendor. To qualify, participants must undergo a third-party audit and inspection of their manufacturing and packaging facilities.   

The company said in a statement posted online that it was never contacted by the FDA about the heavy metal findings or told to take its kratom products off the market.

“Kraken has no information regarding the samples the FDA used in their tests, including when or how the FDA acquired our products or when they tested the samples they obtained,” the statement said.

This isn’t the first time Kraken Kratom has come under FDA scrutiny. Its parent company, PDX Aromatics of Portland, Oregon, recalled thousands of kratom packages last year after samples tested positive for Salmonella bacteria. The company believes the samples that tested positive for heavy metals may have come from an FDA inspection in March, 2018.

“If these samples are from that investigation, their product lots were pulled from the market over 12 months ago as part of the extensive recall we did in cooperation with the FDA. Further, it would indicate that the FDA was rehashing old information, not in an attempt to protect the public, but as a way to target and further stigmatize kratom,” the company said.

In recent years, millions of Americans have discovered kratom, an herb grown and used in southeast Asia for centuries as a natural stimulant and pain reliever. Kratom is widely available online and in smoke shops, but the quality of what’s being sold and what country it came from are often unknown. Like other dietary supplements, kratom products are essentially unregulated and there are little or no quality controls.

That’s one of the reasons the AKA launched its GMP certification program. The organization said it wanted to protect kratom consumers from “unscrupulous vendors using sloppy manufacturing procedures” and those who adulterate kratom to boost its potency by adding substances like fentanyl or morphine.

But under the AKA’s certification program, no kratom products are actually tested for Salmonella bacteria, heavy metals, fentanyl or any other foreign substances.

“No, absolutely not. That is not our function,” AKA President Dave Herman told PNN. “The audit does not inspect the products. The audit inspects the procedures in place to manage the facility.”

Herman says third party auditors hired by the vendor and approved by the AKA only inspect manufacturing procedures — not the kratom itself. He declined to comment on the FDA’s discovery of heavy metals in Kraken Kratom products.

“I have no way of knowing when samples were taken or under what conditions they were taken,” he said. “Was it prior to an inspection? After an inspection? And without that knowledge I’m not sure I can say anything intelligent,” Herman said.

A handful of states have banned kratom and there is speculation the Drug Enforcement Administration will try again to schedule it as a controlled substance, something the agency backed away from in 2016 after a public outcry. FDA commissioner Scott Gottlieb, MD – who leaves office today -- has also mounted an extended public relations campaign against kratom.

"Over the last year, the FDA has issued numerous warnings about the serious risks associated with the use of kratom, including novel risks due to the variability in how kratom products are formulated, sold and used both recreationally and by those who are seeking to self-medicate for pain or to treat opioid withdrawal symptoms,” Gottlieb said in a statement.

“Data suggest that certain substances in kratom have opioid properties and that one or more have the potential for abuse. The findings of identifying heavy metals in kratom only strengthen our public health warnings around this substance and concern for the health and safety of Americans using it."

FDA Takes a Bite Out of Nyloxin

By Pat Anson, PNN Editor

It’s fair to say that cobra venom isn’t high on the list of go-to analgesics for most chronic pain sufferers. But that hasn’t stopped Nutra Pharma from cashing in on the appeal of an exotic, non-opioid pain reliever.

The Florida company’s main product – Nyloxin – is a homeopathic-based medicine that contains a tiny amount of cobra venom, which supposedly contains compounds that block pain signals from reaching the brain. Like other homeopathic products, Nutra Pharma’s CEO says only a small amount of the active ingredient is needed to make Nyloxin sprays and gels effective.

“Our regular strength product is 70 micrograms per milliliter of cobra venom,” CEO Rik Deitsch told PNN. “Our product is based on over a hundred years of research utilizing cobra venom at these dilution levels.”

But a complaint filed last fall by the Securities and Exchange Commission raises doubts about Nutra Pharma claims that it had 1,300 cobra snakes on a Florida farm that it “milks” monthly for venom.

“Nutra Pharma never had a cobra farm, never had cobras, and indeed had never produced cobra venom,” the SEC said.

The only ones getting milked may be Nutra Pharma’s investors. The SEC complaint alleges Deitsch used manipulative insider stock trades and “a series of materially false or misleading press releases” to defraud investors out of nearly $1 million.

This week the U.S. Food and Drug Administration got into the act by sending a warning letter to Deitsch for illegally marketing unapproved products with false claims about their ability to treat chronic health conditions.  

“Today, we posted a warning letter to a company preying on patients who may be seeking alternative treatments for chronic pain, cancers, arthritis and autoimmune and neurological disorders. Health fraud scams like these are inexcusable,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

They may be inexcusable, but they’ve been going on for years with little government oversight. Nutra Pharma’s multi-level marketing touts Nyloxin as “clinically proven to treat moderate to severe chronic pain.” and its website has dozens of glowing reviews from customers.  In a video on its YouTube channel, one customer even claims Nyloxin helped him become the first rheumatoid arthritis sufferer to climb Mt. Everest.   

The FDA commissioner says its time for deceptive marketing claims to end.

“One of our most important obligations is to protect consumers from those who would prey on them with bogus claims and fraudulent products. We’ve dedicated new resources to our enforcement work and I consider these activities the cornerstone of our consumer protection mission,” said Gottlieb. “We’re especially focused on those who would exploit Americans harmed by the opioid crisis with the false promise of products that can treat pain or addiction, but that offer no such benefit.”

It’s good that Gottlieb wants to protect consumers, but he fails to recognize that many Americans are turning to products like Nyloxin because they’re losing access to opioid therapy.  Denied the pain medication that most have safely used for years, patients are experimenting with alternative treatments, including some that are dubious or even fraudulent, such as compounded pain creams and cannabis skin patches.

PNN’s recent survey of over 5,800 patients found that 20 percent had tried medical marijuana or kratom for pain relief. Even more (26%) had used alcohol and a small number (4%) had turned to illegal drugs such as heroin. One in ten said they were getting prescription opioids from family and friends or buying them on the black market — which is being flooded with “Mexican Oxy” and other counterfeit pills laced with fentanyl.

Is it any wonder that people are buying Nyloxin? Or that Nutra Pharma is touting it as a “non-narcotic” and “safe” homeopathic solution to the opioid crisis? In a sense, policymakers have done all the marketing for them.

“I can tell you we have hundreds, if not thousands of people that have reduced or gotten off their opiates with Nyloxin,” said Deitsch, who intends to comply with the FDA request and continue selling Nyloxin. “We are answering the FDA warning letter. We are making the changes to the website and the claims they have asked us to make. But it is a great product and we stand by it.”

FDA Commissioner Resigns Unexpectedly

By Pat Anson, PNN Editor

The head of the U.S. Food and Drug Administration resigned unexpectedly Tuesday, just days after a critical report on 60 Minutes that alleged the FDA “opened the floodgates” to the opioid crisis.  

“I’m immensely grateful for the opportunity to help lead this wonderful agency,” FDA commissioner Scott Gottlieb, MD, tweeted. ”This has been a wonderful journey and parting is very hard.”

In a lengthier statement to FDA staff, Gottlieb cited family reasons for his departure.

“There’s perhaps nothing that could pull me away from this role other than the challenge of being apart from my family for these past two years and missing my wife and three young children,” Gottlieb said, indicating he would remain on the job until next month.

Gottlieb is a 46-year old cancer survivor and a former consultant to several drug companies. He commutes to Washington DC from his home in Westbury, Connecticut, where he lives with his wife and three daughters.   

President Trump tweeted that Gottlieb “has done an absolutely terrific job” and “he and his talents would be greatly missed!”

SCOTT GOTTLIEB, MD

There was no indication that Gottlieb was in trouble or that he was forced out. The FDA is currently involved in a number of complex and controversial regulatory issues, from high drug prices and e-cigarettes to medical marijuana and the opioid crisis.

The timing of Gottlieb’s departure is puzzling, however, because he tweeted two months ago that he had no intention of resigning after hearing from friends about speculation in the news media that he was leaving.

“I want to be very clear — I’m not leaving. We’ve got a lot of important policy we’ll advance this year,” Gottlieb tweeted, adding a famous quote from Mark Twain that reports of his death “have been greatly exaggerated.”

The 60 Minutes report alleged that the FDA caved into lobbying pressure from the pharmaceutical industry in 2001 by changing the warning labels on OxyContin and other opioid medications to indicate they were effective for long term use.

Gottlieb was not working at FDA when the agency made its labeling decision, but pledged last week in a lengthy essay that the FDA would “learn from past mistakes” and take “a much more aggressive approach to regulatory action” involving opioids.

Gottlieb joins a long list of agency directors and cabinet members who have resigned from the Trump administration, including former Health and Human Services Secretary Tom Price, who was forced out over excessive travel expenses and other ethical lapses, and former CDC director Brenda Fitzgerald, who resigned after it was disclosed she invested in tobacco and drug companies.

CBD Is Now Regulated and That May Be a Good Thing

By Roger Chriss, PNN Columnist

The legal status of cannabidiol (CBD) is changing. Once classified exclusively as a Schedule I drug under the Controlled Substances Act, CBD is now legal under federal law. And this means regulation.

The 2018 Farm Bill removed hemp from Schedule I. Hemp is a strain of marijuana with very low levels of THC, but high amounts of CBD.  This has opened the door to a legal market for CBD products, including food and supplements. But there’s a catch. The FDA has strict regulations about CBD being used in dietary supplements or promoted as medical treatments.

“It’s unlawful under the FD&C Act (Federal Food, Drug, and Cosmetic Act) to introduce food containing added CBD or THC into interstate commerce, or to market CBD or THC products as, or in, dietary supplements, regardless of whether the substances are hemp-derived,” FDA commissioner Scott Gottlieb, MD, said in a December 2018 statement.

“Among other things, the FDA requires a cannabis product (hemp-derived or otherwise) that is marketed with a claim of therapeutic benefit, or with any other disease claim, to be approved by the FDA for its intended use before it may be introduced into interstate commerce. This is the same standard to which we hold any product marketed as a drug for human or animal use.”

 The FDA has a FAQ page about cannabis that answers some basic questions:

"Can products that contain THC or cannabidiol (CBD) be sold as dietary supplements? A. No."

"Is it legal, in interstate commerce, to sell a food to which THC or CBD has been added? A. No."

The FDA has reason to be concerned. Product quality for CBD products is iffy at best. An investigation by the NBC affiliate in Miami (see “Patients Are Being Duped”) found that 20 of 35 CBD products tested had less than half the amount of CBD advertised on the label. Some samples had no CBD at all.

Other recent analyses have found THC, pesticides, synthetic cannabinoids and toxic solvents in CBD products.

Moreover, a lack of regulatory oversight has led to an abundance of false, misleading or unsubstantiated claims. A recent review of CBD in the Journal of Clinical Pharmacology found that “CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence.”

There is a lot of research on CBD going back years. The FDA’s approval of the CBD-based drug Epidiolex for rare childhood seizure disorders and a 2018 review that found potential for treating multiple sclerosis symptoms are important indicators of CBD’s medical value. At the same time, researchers have found no benefit in treating spinal cord injury, Crohn’s disease and osteoarthritis.

Yet CBD is now being widely promoted as a wellness product, and added to everything from coffee and pastries to bath oils and mascara. So it is not surprising that the FDA is concerned that people may be duped or put at risk.

The FDA is not alone in this. The New York City Department of Health has banned CBD products from being sold in bars and restaurants. Maine, New York, and Ohio are also banning CBD edibles.

For medically complicated people with chronic illness, regulation could be beneficial. At present these patients face significant risks with CBD products. Tainted CBD may cause unexpected allergic reactions or drug interactions. And contaminated CBD could trigger a positive result on a urine drug test, a common part of pain management amid the opioid crisis. Regulatory oversight could help reduce these risks. 

The legal and regulatory landscape surrounding CBD is shifting quickly. The FDA and state government agencies are watching closely and starting to intervene. This may flush out bad actors in the CBD marketplace and improve product quality and reliability. A stable marketplace with reliable products may be a net gain for the people who stand to benefit the most from CBD.

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 Warns Drug Distributor

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has sent a warning letter to a wholesale drug distributor rebuking the company for its handling of several tampering cases involving oxycodone and other medications.

The letter to the CEO of the McKesson Corporation involves incidents in 2016 when pharmacies notified the company about the tampering and theft of medications it had supplied them with.    

In one such case, a Rite Aid pharmacy in Michigan found that the seal to a bottle labeled as containing 100 tablets of oxycodone had been broken. Inside the bottle a pharmacist found 15 tablets of Aleve, a non-steroidal anti-inflammatory pain reliever.  Two other Rite Aid pharmacies also reported to the company that oxycodone bottles had been tampered with. McKesson investigated the reports and determined the tampering and thefts likely occurred while the bottles were in its possession.  

Similar tampering incidents involved drugs used to treat bipolar disorder, high blood pressure and HIV.

According to the FDA, McKesson did little to identify and quarantine other products in its distribution system that also may have been tampered with and failed to warn other pharmacies that illegitimate products were in the supply chain.

"This is simply unacceptable. A distributor’s failure to have systems in place to investigate and quarantine suspect and illegitimate products within their control is a violation of the law," said FDA commissioner Scott Gottlieb, MD, in a statement.

"But this is even more concerning given that we’re in the midst of a widespread opioid crisis. Opioids that leave the legitimate supply chain could end up being sold illegally, or a patient who was appropriately prescribed these drugs to treat pain may not get the treatment they need or may unknowingly take a medication that’s not meant for them."

The FDA did not say why it waited so long to send the warning letter or notify the public about the 2016 tampering incidents. McKesson is the first company to receive a warning letter under the Drug Supply Chain Security Act (DSCSA), which was enacted by Congress in 2013.

McKesson is one of the largest wholesale drug distributors in the country. It is being sued by dozens of states, cities and counties for its role in the opioid crisis. In 2017, McKesson was fined $150 million for failing to report suspicious orders for oxycodone, hydrocodone and other controlled substances. In 2008, the company agreed to pay $13.25 million in penalties for similar violations.

FDA: Pain Patients Dependent On Opioids Are Not Addicted

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has released new guidance to drug makers to streamline the development of buprenorphine products to treat opioid addiction. Commonly known by the brand name Suboxone, buprenorphine has long dominated the market for addiction treatment.

Of importance to pain patients is a statement about the guideline by FDA commissioner Scott Gottlieb, MD, that seeks to clarify the difference between opioid addiction and patients who need opioids for pain relief.

Gootlieb said there is still stigma and misunderstanding – even in the medical and addiction fields – about the difference between opioid addiction and dependence.

“Because of the biology of the human body, everyone who uses a meaningful dose of opioids for a modest length of time develops a physical dependence. This means that there are withdrawal symptoms after the use stops,” Gottlieb said. “A physical dependence to an opioid drug is very different than being addicted to such a medication.

“Addiction requires the continued use of opioids despite harmful consequences on someone’s life. Addiction involves a psychological preoccupation to obtain and use opioids above and beyond a physical dependence. But someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

“Someone who is physically dependent on opioids as a result of the treatment of pain but who is not craving the drugs is not addicted.”

— Dr. Scott Gottlieb, FDA Commissioner

In recent years new and generic formulations of buprenorphine have been released in tablets, sublingual films, injections and implants, and the FDA is trying to promote the development of more of them.

The guidance released by the agency basically tells drug makers they may be able to submit new drug applications for buprenorphine products without conducting the safety and efficacy trials that are usually required for other medications.

“The guidance we’re finalizing today is one of the many steps we’re taking to help advance the development of new treatments for opioid use disorder, and promote novel formulations or delivery mechanisms of existing drugs to better tailor available medicines to individuals’ needs,” Gottlieb said. “Our goal is to advance the development of new and better ways of treating opioid use disorder to help more Americans access successful treatments.”

There are currently only three drugs approved by the FDA for medication-assisted treatment (MAT) – buprenorphine, methadone and naltrexone. Physicians wishing to prescribe buprenorphine to patients must have a special certification from the DEA and are limited in the number of patients they can treat.

Buprenorphine is an opioid that is also used to treat pain. When combined with naloxone, buprenorphine reduces cravings for opioids and lowers the risk of abuse.

Some addicts have discovered that buprenorphine can also be used to get high or to ease their withdrawal pain from heroin and other opioids. Buprenorphine is such a popular street drug that the National Forensic Laboratory Information System ranked buprenorphine as the third most diverted opioid medication in the U.S. in 2014. 

FDA Pushing for Over-The-Counter Sales of Naloxone

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has launched an “unprecedented” effort to support over-the-counter sales of naloxone, an overdose recovery drug credited with saving thousands of lives. The FDA has developed new drug labeling — at taxpayer expense — to encourage drug makers to start selling naloxone without a prescription.

“This is the first time the FDA has proactively developed and tested a DFL (drug facts label) for a drug to support development of an OTC product. We proactively designed, tested and validated the key labeling requirements necessary to approve an OTC version of naloxone and make it available to patients,” FDA commissioner Scott Gottlieb, MD, said in a statement.

“I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible.”

FDA proposed label for evzio

Curiously, one of the labels the FDA developed would support sales of Evzio, a controversial naloxone auto-injector that sells for about $3,700.

A recent U.S. Senate report accused Kaleo – the company that makes Evzio – of inflating its price by 600% to “capitalize on the opportunity” of a “well established public health crisis.” The report estimates Medicare and Medicaid paid over $142 million in excess costs to Kaleo for its Evzio injectors.

Kaleo has since announced plans for a generic version of Evzio to be available in mid-2019 at a reduced price of $178.

The FDA has also developed an OTC label for Narcan, a naloxone nasal spray that sells for about $135.

Last month, federal health officials called naloxone an “essential element” of government efforts to reduce deaths from opioid overdoses, and urged doctors to co-prescribe naloxone to pain patients talking relatively modest doses of 50 morphine milligram equivalents (MME) or more per day.

The drumbeat for naloxone comes at a time when sales are already booming. According to the healthcare data firm IQVIA, naloxone sales grew from $21 million in 2011 to over $274 million in 2016, and are projected to reach $500 million by 2020. Many of these purchases are made through Medicare or Medicaid, or government funded grants that supply naloxone at no cost to first responders, hospitals and addiction treatment clinics. 

According to one estimate by the CDC, naloxone reversed over 26,000 opioid overdoses from 1996 to 2014, and advocates say the drug has likely prevented thousands of deaths since then.

Earlier this month, naloxone was credited with saving a dozen lives at a suspected fentanyl mass overdose that left one man dead in Chico, California.

“Without that, I’m convinced that we would have had certainly four or five, if not more, additional fatalities,” Chico Police Chief Michael O’Brien told The Los Angeles Times. “There’s no doubt it saved lives.”

Is Naloxone Increasing Opioid Abuse?

There’s no doubt naloxone saves lives, but some researchers say the drug has had little effect on the opioid epidemic and may in fact be making it worse.

In a study recently published by SSRN, an open access online journal, two economics professors said naloxone may raise the risk of an overdose by providing a “safety net” to opioid abusers -- in effect giving them a second chance to abuse more drugs. In an anlaysis of Google search results, they found anecdotal evidence that drug crimes and overdoses increased in states where there was easy access to naloxone.

“Expanding naloxone access increases opioid abuse and opioid-related crime, and does not reduce opioid-related mortality. In fact, in some areas, particularly the Midwest, expanding naloxone access has increased opioid-related mortality. Opioid-related mortality also appears to have increased in the South and most of the Northeast as a result of expanding naloxone access,” wrote Jennifer Doleac, PhD, Texas A&M University, and co-author Anita Mukherjee, PhD, University of Wisconsin.

“Our results show that broad naloxone access may be limited in its ability to reduce the epidemic’s death toll because not only does it not address the root causes of addiction, but it may exacerbate them.”

Doleac and Mukherjee say naloxone may give drug abusers a false sense of security, encouraging them to seek “a higher high” with more dangerous drugs like illicit fentanyl. The researchers said public health officials should prepare for these unintended consequences by offering addiction treatment along with naloxone.

Government-supported efforts to increase naloxone sales are not confined to the federal government. As PNN has reported, a new state law in California requires doctors to “offer” naloxone prescriptions to pain patients deemed at high risk of an opioid overdose. Nothing in the law requires patients to obtain naloxone, yet some pain sufferers say they are being “blackmailed” by pharmacists who refuse to fill their opioid scripts unless naloxone is also purchased. Patients around the country report similar experiences.   

12 Patients Sickened by Contaminated Stem Cells

By Pat Anson, PNN Editor

At least a dozen patients undergoing stem cell therapy developed bacterial infections after being injected with unapproved stem cell products, according to the Food and Drug Administration. Most of the patients were being treated for chronic back and joint pain.

All 12 patients were hospitalized, but there were no deaths. Seven of the infections were in Texas, four in Florida and one was in Arizona.  CDC investigators found E. coli bacteria in unopened vials at two of the stem cell clinics where the patients were treated.   

All of the patients received stem cells derived from umbilical cords that were initially processed by Genetech, a San Diego stem cell manufacturer.  The stem cells were recalled in October and the FDA sent a warning letter to Genetech last month saying its donor selection, manufacturing and safety standards were deficient.

“In this case, the company’s failure to put in place appropriate safeguards may have led to serious blood infections in patients,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

This week the FDA also sent letters to 20 other stem cell providers warning them that the agency would step up its enforcement of guidelines for cell-based regenerative medicine. The FDA has long taken a dim view of newer stem cell therapies that have not undergone clinical testing, but said it would use “enforcement discretion” as long as a new treatment does not pose a significant safety risk.

“The letters we’re issuing today to manufacturers, health care providers and clinics around the country are a reminder that there’s a clear line between appropriate development of these products and practices that sidestep important regulatory controls needed to protect patients. Time is running out for firms to come into compliance during our period of enforcement discretion,” Gottlieb said.  

Gottlieb has previously warned of “unscrupulous actors” in the stem cell industry that deceive patients with “dangerously dubious products.” Critics have complained the agency's "go slow" approach to regnerative medicine has delayed the development of promising new treatments for autoimmune diseases, cancer, diabetes, neuropathy, back pain and other illnesses.  

Is FDA ‘Shadow Ban’ Causing Kratom Shortages?

By Pat Anson, PNN Editor

The American Kratom Association (AKA), an advocacy group for kratom vendors and consumers, came out with an alarming bulletin this week.

“BREAKING: FDA Commissioner Scott Gottlieb is shutting down kratom supplies shipments to the United States. The AKA is running out of time and resources to make sure we can secure the supply chain for you to purchase kratom,” read the post on the AKA’s Facebook page.

The bulletin claimed the FDA was trying to “criminalize kratom users” and then launched into a fundraising appeal asking supporters to “dig deep and send a contribution right now” to the AKA to support its lobbying efforts.

At best, the AKA’s bulletin was premature. At worst, it was misleading. Gottlieb is certainly no friend of kratom, but he’s not issued orders shutting down imports of kratom, an herbal supplement long used as a stimulant and pain reliever in southeast Asia.

The FDA declared an “import alert” for kratom in 2012 and again in 2014 – long before Gottlieb became commissioner – authorizing the seizure of dietary supplements containing kratom. Several large shipments were confiscated as a result of the alert, but clandestine imports of kratom into the U.S. continued largely unchecked.

Kratom has since become widely available online and in many smoke shops, and millions of Americans have discovered kratom can be used to self-treat their chronic pain, anxiety, depression and addiction.

AKA president Dave Herman told PNN the bulletin was based largely on anecdotal reports from a handful of vendors who had kratom shipments confiscated in recent months.  

“I’m sure some of them don’t want to talk about it, but I’ve talked to at least four or five that said their stuff has been grabbed,” Herman said. “I know of one vendor that had a hundred tons literally confiscated.

“We feel from day one that commissioner Gottlieb has been running a shadow ban. It’s clearly an attempt to ban and they’re using any and all portals to do that. But can I hand you a piece of paper (from FDA) that says, ‘We’re doing it?’ No.”

Herman said some kratom vendors are down to a few weeks supply.  

“There’s a lot of fear about what’s going on out there,” he said.

Kratom Demonized

Inflammatory rhetoric and scare tactics have become increasingly common in the escalating debate over kratom.

Gottlieb publicly calls kratom an “opioid” – even though its active ingredients are alkaloids -- while claiming there is “no evidence to indicate that kratom is safe or effective for any medical use.” Last year, the FDA claimed dozens of fatal overdoses were associated with kratom, while admitting nearly all of the deaths involved other drugs and “could not be fully assessed.”

Several kratom products were recalled earlier this year during an FDA and CDC investigation of a small salmonella outbreak associated with the herb. Although the source of the outbreak was never identified and only about 200 people were sickened, Gottlieb said “anyone consuming kratom may be placing themselves at a significant risk of being exposed to salmonella.”

More recently, Ohio health officials have claimed kratom produces a “heroin-like high” and was being used intravenously by drug addicts – a notion that most kratom users found preposterous.

“Who the hell is injecting kratom? These people are out of their minds,” one reader told us.

The FDA did not directly respond to a request for comment on the AKA’s bulletin, only saying that “certain kratom products and importers” were targeted in its 2012 import alert. But Herman says it is clear to him what’s happening in 2018. “It’s a full demonization. I don’t think there is any doubt about that,” he said.

Herman believes federal health officials may be trying to avoid scheduling kratom as a controlled substance, something the DEA tried and failed to do in 2016 after a public outcry.  Scheduling kratom would require a public comment period and likely get Congress involved, which the FDA can avoid with a “shadow ban.”

“It’s a concerted effort. There is a (kratom) shortage out there. The shortage didn’t exist previously,” Herman said. “The range I’ve heard of any (vendor) inventory is the highest is 6 months and the lowest is two weeks. There’s definitely a movement there and its harder and harder to get the product into the country.”

When asked if the AKA bulletin could incite fear and lead to hoarding and price increases, Herman was circumspect.

“Some people will stock up. Some won’t,” he said. “How people react, I can’t anticipate. I don’t know the answer to that. I do know that’s there’s a shortage of product. And I think prices have already risen, best as I can tell.”   

FDA Expands Safe Prescribing Program for Opioids

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration will require that educational training in pain management and safe opioid prescribing be offered to all healthcare providers under a major expansion of the agency’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) program.

REMS is also being expanded to include immediate-release (IR) opioids such as hydrocodone, oxycodone and morphine. Until now, REMS regulations only applied to extended-release and long-acting (ER/LA) opioid analgesics, such as OxyContin and Exalgo. Warning labels will be updated for all IR opioids, which account for about 90 percent of opioid pain medications.

“Many people who become addicted to opioids will have their first exposure in the medical setting,” said FDA Commissioner Scott Gottlieb, MD, in a statement. “Today’s action, importantly, subjects immediate-release opioids – which are the most commonly prescribed opioid products – to a more stringent set of requirements.”

The REMS program was first established in 2012. It required manufacturers of ER/LA opioids to pay for continuing education programs for prescribers only. Updated educational content must now also be provided to nurses, pharmacists and other healthcare providers who seek it. The training will cover broader information about pain management, including alternatives to opioids for the treatment of pain.

The training is not mandatory, but the FDA is considering whether to require continuing educational programs in pain management and safe prescribing.

“The agency believes that all health care providers involved in the management of patients with pain should be educated about the safe use of opioids so that when they write or dispense a prescription for an opioid analgesic, or monitor patients receiving these medications, they can help ensure the proper product is selected for the patient and used with appropriate clinical oversight,” the agency said.

“I think these changes to the REMS are very good and long overdue,” said Bob Twillman, PhD, Executive Director of the Academy of Integrative Pain Management. “We know that the IR opioids are much more highly sought-after, versus ER/LA opioids, for purposes of abuse, and there is absolutely no reason why they (and their manufacturers) should be exempt from this requirement.  

“I’m not concerned, at this stage, about this change causing primary care providers to back off on prescribing, given that participation in the program is still completely voluntary for healthcare providers. If this voluntary status changes, and FDA finds a way to make REMS education mandatory, I will be concerned that some providers will opt out of prescribing opioids altogether.”

The FDA’s action greatly expands the number of opioid products covered by REMS from 62 to 347 opioid analgesics. The updated warning labels will strongly encourage providers to complete a REMS education program, and to counsel patients and caregivers on the safe use of opioid medication.

“Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids and fostering rational prescribing to enable appropriate access to those patients who have legitimate medical need for these medicines,” said Gottlieb.

Opioid prescriptions in the United States fell sharply during the first half of 2018 and now stand at their lowest levels since 2003, according to data released last month by the FDA. The trend appears to be accelerating as many doctors lower doses, write fewer prescriptions or simply discharge pain patients.

While opioid prescriptions decline, overdoses continue to rise. According to preliminary data from the CDC, nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl, heroin and counterfeit drugs, not prescription opioids.

Opioid Prescriptions Plunge to 15-Year Low

By Pat Anson, Editor

The volume of opioid prescriptions in the United States has fallen sharply and now stand at their lowest levels since 2003, according to data released by the Food and Drug Administration.

Over 74 million metric tons of opioid analgesics were dispensed in the first six months of 2018, down more than 16 percent from the first half of 2017. Opioid prescriptions have been declining for several years, but the trend appears to be accelerating as many doctors lower doses, write fewer prescriptions or simply discharge pain patients.

“These trends seem to suggest that the policy efforts that we’ve taken are working as providers, payers and patients are collectively reducing some of their use of prescription opioid analgesic drugs,” said FDA commissioner Scott Gottlieb, MD, in a statement.

SOURCE: FDA AND IQVIA

"This graph confirms the perception that many of use have, that prescribing continues to decline," said Bob Twillman, PhD, Executive Director of Academy of Integrative Pain Management. "But, the question remains --what is the effect of this decreased prescribing on people with chronic pain?

"Measures of prescribing need to be matched with measures of patient function and quality of life, especially given evidence that decreased prescribing may actually be associated with increased suicide. All this measure really tells us is that the intense pressure from legislators, regulators, and payers has had its desired effect of driving down prescribing, even it there’s no evidence that it’s done anything else helpful."

While opioid prescriptions decline, overdoses continue to rise. According to preliminary data from the CDC, nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl and heroin, not prescription opioids.

“It isn’t necessarily the case that more people are suddenly switching from prescription opioids to these illicit drugs. The idea of people switching to illicit drugs isn’t new as an addiction expands, and some people have a harder time maintaining a supply of prescription drugs from doctors,” said Gottlieb. “What’s new is that more people are now switching to highly potent drugs that are far deadlier. That’s driven largely by the growing availability of the illicit fentanyls.”

Illicit fentanyl and its chemical cousins are synthetic opioids, 50 to 100 times more potent than morphine. They are produced largely by clandestine drug labs in China and then smuggled into the U.S., where they are often mixed with heroin, cocaine and counterfeit drugs.  A record 1,640 pounds of fentanyl and nearly 5,500 pounds of heroin have been seized by law enforcement so far this year; likely a small fraction of what’s available on the black market.

While the Trump administration has expanded efforts to stop the distribution and sale of illicit opioids, it also remains focused on reducing the supply of prescription opioids.  The FDA plans to develop new prescribing guidelines for treating short-term, acute pain that will likely set a cap on the number of pills that can be prescribed for certain medical conditions.

“No more 30-day prescriptions for a tooth extraction or an appendectomy,” said Gottlieb.

The Justice Department also recently announced plans to lower production quotas by 10% next year for six widely prescribed opioid medications. The goal of the administration is to reduce opioid prescriptions by a third in the next three years. 

“The number of opioid prescriptions is only one of many factors and may not be the most important factor contributing to the opioid crisis. In fact, the U.S. is at a 15-year low in the amount of opioid prescribed but continues to see a surge of drug overdoses,” said Lynn Webster, MD, a pain management expert and past president of the American Academy of Pain Medicine.

“Much of the effort to curb the amount of prescription opioids has contributed to more suffering by people in chronic pain and possibly the increase in suicides.  It also hasn't done anything to curb the number of overdose deaths. Rather than being focused on number of pills or amount of opioid prescribed we need to focus on what is the best and most appropriate treatment for individual patients. When that is done properly, the right amount of opioids will be prescribed.”  

FDA to Develop Acute Pain Guidelines

By Pat Anson, Editor

The head of the U.S. Food and Drug Administration is following up on a promise to develop new federal prescribing guidelines for treating short-term, acute pain. But don't expect an overhaul of the CDC's controversial opioid guideline.

FDA commissioner Scott Gottlieb, MD, announced today that his agency has awarded a contract  to the National Academies of Sciences, Engineering, and Medicine (NASEM) to help develop guidelines for prescribing opioids for acute pain that results from specific medical conditions or procedures, such as wisdom tooth removal or post-operative pain.  

The CDC guideline takes a one-size-fits-all approach to chronic pain -- pain that lasts longer than three months -- and doesn't distinguish between pain from fibromyalgia, arthritis, neuropathy or any other medical condition.  

"We’ve contracted with NASEM to conduct a consensus study and issue a report on its findings. This work will begin with an identification and prioritization of procedures and conditions associated with acute pain for which opioid analgesics are commonly prescribed and where evidence-based clinical practice guidelines would help inform prescribing practices," Gottlieb said in a statement.

"We acknowledge the work of our colleagues at the U.S. Centers for Disease Control and Prevention (CDC) who have taken an initial step in developing federal guidelines on pain management and the use of opioids which are based on expert opinion. Our work seeks to build on that work by generating evidence-based guidelines where needed. The guidelines we generate would be distinct from this corresponding effort by the CDC, in that our effort would be indication-specific." 

Importantly, Gottlieb says NASEM will hold a series of public meetings and workshops, and seek input from "a broad range of stakeholders" from different medical specialties. The CDC guideline was initially developed with no public hearings and with little input from pain management experts.

While Gottlieb clearly wants more transparency brought to the guideline development process, he also clings to the notion that opioid medication is overprescribed and is primarily responsible for the nation's opioid crisis.

"Many people who become addicted to opioids will first be exposed to these drugs through a lawfully prescribed medication. Unfortunately, the fact remains that there are still too many prescriptions being written for opioids," Gottlieb said.

"Our analyses suggest that the first prescription for many common, acute indications could typically be for many fewer pills – maybe just a day or two of medication rather than a 30-day supply, which is typically prescribed. In some cases, the excess pills that aren’t used by patients may end up being diverted to illicit markets or misused or abused by friends or family members. In other cases, patients who are prescribed more medication than necessary may find themselves at increased risks for misuse, abuse and addiction."

But studies show that long-term opioid use by patients recovering from surgery is rare and less than one percent of legally prescribed opioids are diverted.

In 2016, the American Pain Society released guidelines that encourage physicians to limit the use of opioids and offer “multimodal therapies” to patients suffering from postoperative pain. Among the treatments suggested are pregabalin, gabapentin, NSAIDs and acetaminophen.

The University of Michigan has also developed prescribing guidelines for over a dozen common surgeries, ranging from hernia repair to hysterectomies. The recommendations list the suggested dose of opioids and number of pills for each procedure.      

Several states have already adopted their own guidelines for acute pain, limiting opioids to a few days' supply -- regardless of whether the pain is from a broken leg, a tonsillectomy or gunshot wound.  It's not clear how federal guidelines for acute pain would impact state regulations.

FDA Warns Veterinarians of Pet Owners Abusing Opioids

By Pat Anson, Editor

Doctors and patients aren’t the only ones under scrutiny for prescribing and using opioid pain medication. Pet owners are also coming under suspicion for diverting and abusing opioids intended for their animals.

The Food and Drug Administration today warned veterinarians to be cautious when prescribing opioids and be on the alert for people who may be using their pets to gain access to the drugs.

“We recognize that opioids and other pain medications have a legitimate and important role in treating pain in animals – just as they do for people,” FDA commissioner Scott Gottlieb, MD, said in a statement.

“But just like the opioid medications used in humans, these drugs have potentially serious risks, not just for the animal patients, but also because of their potential to lead to addiction, abuse and overdose in humans who may divert them for their own use.”

Only one opioid is currently approved by the FDA for use in animals, a potent fentanyl medication for post-surgical pain that is sold under the brand name Recuvyra.  

The maker of another fentanyl based product -- carfentanil -- voluntarily surrendered approval for the drug in March because of growing signs it was being diverted. Carfentanil is so potent it was used by veterinarians as an anesthetic on elephants.   

With few options to choose from, some veterinarians are legally prescribing tramadol and others opioids intended for humans to relieve pain in pets. The FDA is recommending veterinarians use alternatives to opioids whenever possible and look for signs of opioid abuse by pet owners and their own employees.

“We’re advising veterinarians to develop a safety plan in the event they encounter a situation involving opioid diversion or clients seeking opioids under the guise of treating their pets; and taking steps to help veterinarians spot the signs of opioid abuse,” Gottlieb said.

Possible warning signs of opioid abuse are suspicious injuries to animals, a pet owner asking for specific medication by name, or asking for refills of lost or stolen medication.

Gottlieb’s statement was released one week after a small study published in the American Journal of Public Health suggested that some pet owners are purposely injuring their animals to gain access to opioids.

"Our results indicate that we should be paying more attention to how opioid abusers are seeking their drugs -- including through veterinary clinics," said Lili Tenney, deputy director of the Center for Health, Work & Environment at the Colorado School of Public Health.

In a survey of 189 Colorado veterinarians, 13 percent reported they had seen a client who they believed had purposefully injured a pet or made them ill. Nearly half the vets said they knew of a pet owner or employee who was abusing opioids; and 12 percent suspected a staff member of diverting opioids or abusing them.

Colorado and Maine require veterinarians to look at a pet owner’s medication history before dispensing opioids or writing a prescription.  Over a dozen states require veterinarians to report when they prescribe opioids to a prescription drug database.