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.   

Some California Pain Patients Forced to Buy Naloxone

By Pat Anson, PNN Editor

A new state law that mandates new prescription pads isn’t the only headache faced by doctors and pain patients in California.

Over a dozen bills passed by the state legislature and signed into law by former Gov. Jerry Brown are aimed at addressing the opioid crisis. One of them -- AB 2760 -- requires doctors to “offer” a prescription for naloxone to any patient deemed at high risk of an opioid overdose.  Naloxone (Narcan) rapidly reverses the effects of an opioid overdose and has been credited with saving thousands of lives.

The naloxone law does not require patients to fill the prescription, but some pain sufferers are being forced by pharmacists to buy naloxone if they want to get their opioid medications filled. For one patient, it was a choice between pain relief and putting food on the table.

“A medication I don't want, don't need, and didn't ask for, is being forced on me. As in holding my other medication hostage. And each dose of Narcan is $75 for the uninsured. Which I am, because my insurance company won't pay for it,” one reader wrote on PNN’s Facebook page.

“I had to go without groceries to purchase a medication I didn't want, need or ask for. Nine years of never ever breaking a rule, having any adverse effects EVER, and never failing all those ‘gotcha’ tests they inflict on pain patients. So now, in addition to being in pain, I'm hungry. This cannot be.”

Another pain sufferer said she felt treated like a drug addict when a pharmacist forced her to buy Narcan, a nasal spray that contain naloxone.

“Blackmailed by Kaiser to pay $50 for Narcan before they would give me my pain meds. I am retired, disabled, and on fixed income,” wrote a woman who lives with severe arthritis. “I was an RN who worked holidays, weekends, nights, etc. Now this ‘greatest’ country treats me like some scum addict who shoots up illegal drugs.”

The requirement that doctors offer a naloxone prescription applies to so-called “high-risk” patients taking over 90 MME (morphine milligram equivalents) of opioids a day or those who are co-prescribed benzodiazepines, an anti-anxiety medication. Patients who have previously overdosed or have a history of substance abuse are also considered high risk.

But whether high-risk or low-risk, nothing in the law requires a patient to buy naloxone or empowers a pharmacist to withhold medications.

“The law does not make it mandatory for the patient to accept a prescription for naloxone or to fill it but only for the patient and physician to have a thoughtful conversation about whether it would be in the best interest of the patient,” Assemblyman Jim Wood, the bill’s sponsor, said in a statement to PNN.

“The law does not make it mandatory for the patient to accept a prescription for naloxone or to fill it.”

— CA Assemblyman Jim Wood

“We are beginning to hear circumstances where patients are being required to fill the naloxone prescription, and will investigate the circumstances where this is happening because that is not what the law states.”

Naloxone costs only pennies to make and syringes containing generic versions of the drug typically cost about $15 each. Branded and formulated versions such as Narcan are more expensive.

Evzio, a kit that contains two auto-injectors of naloxone, retails for about $3,700 and its manufacturer has been accused of price gouging.  The company reportedly raised Evzio’s price by over 600% to “capitalize on the opportunity” of a “well established public health crisis.”

Whether it comes in a spray, injector or syringe, its impractical to expect anyone to give themselves a dose of naloxone.

“What the state and others fail to realize is many pain patients live alone. Even if one were to accidentally overdose and lose consciousness how are they supposed to administer the Narcan?” asks PNN columnist Rochelle Odell, who lives in California. “No one clearly thinks these grandiose ideas through.”

Law enforcement groups, pharmacists and the Medical Board of California supported passage of AB 2760, but the bill was opposed by the Academy of Family Physicians, American College of Emergency Physicians and the California Medical Association (CMA).

“Mandating that a specific medication be prescribed in a variety of situations, regardless of the individual patient characteristics, is inappropriate and places the government between a patient and his or her physician,” the CMA said.

Despite that warning, AB 2760 was passed unanimously by the state Assembly and Senate, signed by the governor, and became law on January 1st.

Prescription Pad Chaos

As PNN has reported, the law of unintended consequences also applies to AB 1753, which requires California doctors to use customized prescription pads for opioids that have uniquely serialized identification numbers.

The idea was to prevent counterfeiting and get more prescriptions filed electronically, but instead the early weeks of the law’s implementation have been marked by chaos. Many doctors were unaware of the new law or unable to get new prescription pads ordered before January 1st. As a result, pharmacists have refused to fill prescriptions written on old pads and patients have been sent away empty-handed.

“I just got my new prescription pads (Monday) at a cost of several hundred dollars, and the change is trivial,” Dr. Richard Buss, a family practice physician in Jackson, told the Sacramento Bee. “At the hospital here, I was next to a doctor who was trying to send a patient home after knee surgery, and the pharmacy wouldn’t honor his prescription because they were old forms.” 

Buss said this is the second year in a row that California doctors were not given proper notification of changes in their prescription pads. 

“They’re just changing prescription requirements, and then the doctors have to jump through the hoops suddenly, and I’m left with thousands of prescription blanks that are unusable, and that’s probably true for a lot of other doctors,” he said. 

Assemblyman Evan Low, who sponsored AB 1753, was unavailable to comment to PNN. In a January 7 letter to California’s Attorney General, Low blamed state regulators for the “unanticipated” confusion caused by his legislation. 

“I have been informed that numerous pharmacies have already turned away individuals holding prescriptions written on unserialized forms that are otherwise valid; in the face of possible discipline, dispensers are forced to decide between denying care to their patients and risking action against their license,” Low wrote. 

The California Medical Association is drafting new legislation to ensure a smoother transition to the new prescription pads, a process that usually takes weeks or months.

Feds Urge Doctors to Co-Prescribe Naloxone

By Pat Anson, PNN Editor

Pain patients taking relatively modest doses of opioid medication should be co-prescribed naloxone, according to a recommendation released this week by the U.S. Department of Health and Human Services.

Naloxone is an overdose recovery drug administered by injection or nasal spray that rapidly reverses the effects of an opioid overdose. It has been credited with saving thousands of lives, although recently there has been controversy over a company exploiting demand for the drug by raising the cost of its naloxone injector over 600 percent.

“Given the scope of the opioid crisis, it’s critically important that healthcare providers and patients discuss the risks of opioids and how naloxone should be used in the event of an overdose,” said Adm. Brett Giroir, MD, assistant secretary for health and senior advisor for opioid policy at HHS.

“Co-prescribing naloxone when a patient is considered to be at high risk of an overdose, is an essential element of our national effort to reduce overdose deaths and should be practiced widely.”

But the “guidance” released by HHS could involve millions of patients who are not necessarily at high risk and have been taking opioids safely for years.  It urges doctors to “strongly consider” prescribing naloxone to patients under these circumstances:

• Patients prescribed opioids at a dose of 50 morphine milligram equivalents (MME) or more per day

• Have respiratory conditions or obstructive sleep apnea (regardless of opioid dose)

• Have been prescribed benzodiazepines (regardless of opioid dose)

• Have a mental health or non-opioid substance use disorder such as excessive alcohol use

• Are receiving treatment for opioid use disorder

• Have a history of illegal drug use or prescription opioid misuse

The HHS guidance was issued days after an FDA advisory committee voted 12 to 11 in favor of adding language to opioid warning labels recommending that naloxone be co-prescribed.  Some panel members objected to the labeling because of the additional cost involved and because it does not address deaths caused by illicit opioids, which account for the vast majority of opioid overdoses.

The guidance notes that most health insurance plans, including Medicare and Medicaid, will cover at least one form of naloxone. For patients without insurance, the guidance suggests contacting a state or local program that may supply naloxone for free or at low cost.

Naloxone costs only pennies to make and syringes containing generic versions of the drug typically cost about $15 each. But formulated and branded versions that have a more sophisticated delivery system are much pricier. According to Health Care Bluebook, a package of two nasal sprays of naloxone sold under the brand name Narcan will cost about $135.  Evzio, a kit that contains two auto-injectors of naloxone, retails for about $3,700.   

A recent U.S. Senate report found that Kaleo, a privately-owned drug maker, jacked up the price of Evzio by over 600% to “capitalize on the opportunity” of a “well established public health crisis.” As a result, the report estimates the U.S. government paid over $142 million in excess costs to Kaleo for prescriptions covered by Medicare.  

The new HHS guidance mirrors that of the 2016 CDC opioid guideline, which encourages physicians to consider prescribing naloxone to pain patients on “higher opioid dosages” of 50 MME or more.

“I’m personally against it, because I don’t think most patients who require opioids for pain management are at risk of overdose,” said Andrea Anderson, Executive Director, Alliance for the Treatment of Intractable Pain (ATIP).  “I also don’t think naloxone helps unless you’re with other people, which makes more sense for those who are using illicit opioids rather than those who rely on opioids for routine pain relief. 

“I don’t think the government should require patients to buy medications for which they do not have a proven need. This sounds like another one of those good ideas in theory but poor in practice.”

The New Cruelty Rolls On

(Editor’s note: Rob Hale is a 52-year old Missouri man who lives with late-stage Ankylosing Spondylitis, a degenerative and incurable form of arthritis. We’ve written before about Rob and his difficulty in getting opioid pain medication – what he calls the “New Cruelty.”)

By Rob Hale, Guest Columnist

I’m here to talk about what happens when someone like me, who already is criminally undermedicated, gets seriously injured and must deal with the new procedures for treating chronic pain patients.

On August 16th of this year, I slipped and fell, breaking my neck.  I know, I know – bad idea. 

When I was brought into the hospital, they immediately hit me up with a dose of Narcan (naloxone), a drug used to reverse opioid overdoses. Narcan takes all the opiates out of your system in about 20 minutes, so you can feel every last iota of pain in your body. You also get to go through about a week’s worth of withdrawal pains in just under a half hour. Narcan is now standard operating procedure for any patient who comes into the ER with any form of opiate/opioid in his or her system. 

Anyway, back to the fun.  I was drifting in and out of consciousness due to the pain, while they took x-rays and CT scans of my neck. It turned out that I had a minor fracture, so they decided it was time to slit me from my skull to my mid back and put two, 12-inch titanium rods and 13 fittings and screws into my spine. 

I vaguely remember agreeing to this and putting my ‘X’ on some sheet of paper saying they could do it.  One thing I do remember clearly is I made damned sure that once the surgery was over and I was sent home, that I was going to get at least 6 and probably 12 days’ worth of pain medication.  I was assured of this not only by the neurosurgeon, but by all the interns and nurses who were attending me. 

I only spent 4 days in the ICU recovering from this nightmare of a surgery when they told me I was ready to go home!  I was shocked since they had just removed the wound drains that very day.  

But I really did want to get home and see my dog and my family, so I thought, “Okay, they must know what they’re doing, right?” 

I want you to guess what happens next, kids!

You guessed it – they were finishing up my discharge papers and I asked about my scripts.  They said that because I already had a pain management doctor, that is was up to him to provide me with the meds that I would need to recover from the surgery.  I explained, just as I had before the surgery, that my pain doctor was not going to be able to see me for several weeks, because his primary clinic is three hours away in Park City, Kansas and he is only in Kansas City one week out of the month.  Of course, I called him and begged for help, but to no avail. 

While I was recovering in the hospital, I was getting long-acting morphine 3x daily, plus immediate release oxycodone every 4 hours.  When I was released from the hospital, they gave me oxycodone to take every 6 hours, and no long acting morphine at all. 

Within 3 or 4 days, I lost the ability to use my right leg at all.  Having no other medication, nor any other recourse, I decided to use some of the methadone that I had left over from my last palliative care doctor. Unfortunately, it was about 10 years old.  But what was I to do?  It was that or hit the streets and try to get some illegal medication, which might have killed me since that crap is often loaded with illicit fentanyl. 

I was very careful to keep track of what I was taking, but I am guessing the methadone had gone bad, because I had a serious reaction to it and my dad called in the paramedics again. 

So, it was back to the hospital for me! Four days in ICU and 5 days in a semi-private room with a roommate who had pneumococcal pneumonia and a toilet that didn’t work, before I was  transferred to a nice, private room.  Only 2 days there, before they sent me over to a physical therapy facility across the street, where they tried to get my leg to work. 

All the doctors there were totally on board with the New Cruelty.  One actually told me that people who took more than 90 MME (morphine milligram equivalent) were at a much higher risk of death! It’s amazing to me how quickly they have disseminated this propaganda, and how completely the new generation of doctors have accepted it as the truth! 

This nonsense has gone on for years and I am becoming more and more despondent with this opioidphobic world. If you know me, you know that I live with chronic pain.  Not just any old pain, mind you – it’s really bad.  I have Ankylosing Spondylitis in its most advanced form, which more or less means that my spine, neck and sacroiliac are completely fused.  This has caused me daily intractable pain. I’m talking about pain that would drop the average person to his or her knees, praying to God to take their lives away just so the pain would stop. 

Adequate Care Phase

I am not attempting to elicit sympathy. It does nothing to ease the unending, merciless, wicked, 9 out of 10 pain that I live with day in and day out, 7 days a week, and 365 days a damned year. 

For many years, my pain was well controlled with morphine and hydromorphone. I was taking over 1,000 MME a day and never felt better in my life.  During this time, which I like to call my “adequate care phase,” which lasted almost 12 years, I never misused my medications and even went so far as to keep a journal listing every single pill that I took. My palliative care doctor can back me up on this. He was very surprised yet pleased to see how carefully I was using these drugs and how much respect I had for them.  I knew they were potentially deadly and dangerous, but while I was taking them – exactly as prescribed – I was every bit as lucid and well-spoken as I am right now. 

You see, when you have extreme amounts of pain, opioids go straight to the pain – they do NOT cause any type of high or euphoria.  I was able to participate in family functions, help around the house and assist my aging parents -- in short, to live a semi-normal, quasi-productive life.  I even opened my own little guitar shop out of my house, to make a little money to supplement my rather meager social security disability income. 

Then came the New Cruelty, in the form of a supposedly voluntary set of opioid guidelines from the CDC — or as I like to call them, the medical Gestapo.  According to the CDC, I was at high risk of overdose for over a decade because I was taking over 90 MME.

We are now at the mercy of a medical industrial complex that – in collusion with insurance companies and psycho-sociopaths in Congress – have created a fear-based campaign that they have dubbed the “opioid epidemic’ or “opiate crisis.” I firmly believe that chronic pain patients are being targeted for death by this campaign, either by our own hands or by medical complications that result from being woefully undermedicated. 

Rob Hale lives in Kansas City, MO. He was diagnosed with Ankylosing Spondylitis at the age of 27.

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

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

FDA Speeds Approval of Naloxone Nasal Spray

By Pat Anson, Editor

It usually takes years for the Food and Drug Administration to approve a new medication.

But it took less than four months for the agency to give the okay to Narcan, the first FDA approved nasal spray containing naloxone, an emergency life-saving medication that can stop or reverse the effects of an opioid overdose.

Opioids – both legal and illegal – can suppress breathing and cause sleepiness. When someone overdoses on an opioid they may fall asleep and be hard to wake, and their breathing can become shallow or even stop – leading to brain damage or death. If naloxone is administered quickly, it can counter the overdose effects, usually within two minutes.

“Combating the opioid abuse epidemic is a top priority for the FDA,” said Stephen Ostroff, MD, acting commissioner of the FDA. “While naloxone will not solve the underlying problems of the opioid epidemic, we are speeding to review new formulations that will ultimately save lives that might otherwise be lost to drug addiction and overdose.”  

image courtesy of adapt pharma

Until now, naloxone was only approved in injectable forms, usually in a syringe or auto-injector. Many first responders and emergency room physicians felt a nasal spray formulation of naloxone would be easier and safer to deliver.

Narcan does not require assembly and delivers a consistent, measured dose of naloxone. It can be used on adults or children, according to the FDA, and is easily administered by anyone. The drug is sprayed into one nostril while the patient is lying on their back, and can be repeated if necessary.

The FDA granted fast track review of Narcan in July after a getting a new drug application from a unit of Adapt Pharma, which is based in Ireland.  In clinical trials, a single 4 mg dose of Narcan delivered the same levels of naloxone in about the same amount of time as an injection.

“We heard the public call for this new route of administration, and we are happy to have been able to move so quickly on a product we are confident will deliver consistently adequate levels of the medication – a critical attribute for this emergency life-saving drug,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

The use of Narcan in patients who are opioid dependent may result in severe withdrawal symptoms, such as body aches, diarrhea, increased heart rate, fever, runny nose, sneezing, sweating, nausea or vomiting, shivering and abdominal cramps.

Adapt Pharma says Narcan will be available after the first of the year and will initially have a “public interest price” of $75 for a package of two doses when ordered by public health  organizations.  The company has not disclosed pricing for other purchasers using private insurance or paying in cash.

“Anyone who uses prescription opioids for the long term management of chronic pain, or those who take heroin, are potentially at risk of experiencing a life-threatening or fatal opioid overdose where breathing and heart beat slow or stop,” the company said in a statement.