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.

Kraken_Kratom_Logo.png

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.

logo@2x.png

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.

Nyloxin.png

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

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 tweet.png

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.”

marijuana oil.jpg

 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.jpg

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.

129.jpg

"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.

bigstock-Addiction-Diagnosis-Medical-C-120768788.jpg

“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

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?

1024px-Naloxone_2_(cropped).jpg

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.