Opinion: Why Zohydro Ban Is A Tough Call

Update 4/15:

The AP reports that a federal judge blocked Massachusetts from banning the powerful new painkiller Zohydro.

U.S. District Court Judge Rya Zobel on Tuesday issued the preliminary injunction after the maker of the drug, Zogenix, said in a lawsuit that the ban ordered by Gov. Deval Patrick was unconstitutional.

Zobel said in issuing the injunction that Massachusetts appears to have overstepped its authority in banning the drug, which had been approved by the U.S. Food and Drug Administration.

Patrick ordered the ban after declaring a public health emergency in light of widespread prescription drug abuse in the state.

The judge said federal law preempted the state’s order.

By Judy Foreman
Guest contributor

U.S. District Court Judge Rya W. Zobel today disappointed anyone who expected her to quickly strike down Gov. Deval Patrick’s ban on the sale of the new pain reliever Zohydro. She declined to rule on the drugmaker’s request to quickly but temporarily lift the ban, and is continuing to consider whether to lift the ban permanently.

Judge Zobel faces a difficult decision but not because Zohydro, as many media reports have said, is more potent than anything else on the market. It’s not, and we’ll get to that in a minute.

(wikimedia commons)

(Wikimedia Commons)

First, the legalities. It should be up to federal health officials, including the U.S. Food and Drug Administration, not governors, to make decisions about the safety (or lack thereof) of drugs. For better or worse, the FDA, after a long 2013 review, and against the vote of its own advisory committee, did approve Zohydro in October of last year.

Legally, and logically, it also made little sense in the first place – except politically — for a governor to focus on one particular drug when the whole class of drugs to which it belongs — opioids, also known as narcotics – is controversial precisely because that whole class of drugs has such a complex mix of risks and benefits.

In truth, Zohydro is probably not the wonder drug that its manufacturer, Zogenix, claims, nor is it the menace that critics assert. The furor over Zohydro is simply the latest example of how difficult it is to balance the legitimate needs of people in chronic pain who need long-acting opioids and the also-legitimate need to protect vulnerable people from getting their hands on drugs they might abuse.

The unique feature of extended-release Zohydro is that it contains the opioid hydrocodone, and only hydrocodone. Other hydrocodone-containing drugs such as Vicodin contain both hydrocodone and acetaminophen (the active ingredient in Tylenol.) Strange as it may seem, it’s the acetaminophen that is often the dose-limiting ingredient because it can cause serious liver toxicity. So, in that sense, a hydrocodone-only pill is a step forward.

Zohydro is likely to lose its unique status soon. Purdue Pharma has just finished Phase 3 trials on its own extended release hydrocodone-only product, which still has to go through the FDA approval process.

A major criticism of Zohydro is that it was approved without having tamper-resistant features built in. Zogenix spokeswoman Catherine O’Connor said in a telephone interview that the company is working on two approaches to tamper-resistance now.

Why the FDA would allow a non-abuse-deterrent form of Zohydro on the market is a mystery to many, among them pharmacologist and neuroscientist June Dahl of the University of Wisconsin.

Dahl, who has studied pain drugs for decades, said in a telephone interview that it’s a good thing to have a hydrocodone-only pain reliever on the market because it gives pain patients another option. But she asks, “Why in the devil did the FDA allow this formulation to get approval? It seems like a disaster waiting to happen.”

On the other hand, it’s not clear how helpful abuse-deterrent forms of opioid pain relievers actually are.

“I would love if we had abuse-deterrent formulations that were actually meaningful and effective at deterring abuse in all instances. We are moving in that direction,” Dr. Margaret Hamburg, the FDA Commissioner, told a senate panel in March. But, she added, “Right now, unfortunately, the technology is poor.”

One problem is that, even when pills are manufactured so that they are harder to chew or crush (which addicts do in order to snort or inject the drug), determined abusers can simply swallow handfuls of the pills to get the high they are looking for.

Another problem is that abuse-deterrent formulations can actually spur some abusers to turn to heroin. That’s what happened when Purdue began marketing an abuse-deterrent form of OxyContin in 2010. It worked — in the narrow sense that, because it turned to a mushy gel when chewed or ground up, it couldn’t be snorted or injected. But an unintended side effect was that frustrated abusers turned to heroin.

In a July, 2012 letter to the New England Journal of Medicine, for instance, researchers from Washington University reported that the percent of drug abusers who chose OxyContin as their primary drug of abuse dropped from 36 percent before the release of the abuse-deterrent form to 13 percent – and their use of heroin almost doubled.

So what are the real risks and benefits of Zohydro? Here’s what FDA spokeswoman Sandy Walsh wrote in answer to that question:

First of all, she stressed that the FDA approved Zohydro because it is a “new option for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatments…are inadequate.”

Unlike the combination hydrocodone products, Zohydro “can be taken without the threat of severe liver damage,” she noted. People who are prescribed Zohydro will probably be those pain patients who are already taking other opioids – in other words, they will be switched to Zohydro. Thus, Walsh wrote, the total number of pain patients taking opioids may not be increased: “We anticipate Zohydro will take a slice of the market away from other opioids, and not expand the opioid market in general.”

As Walsh went on to note in her email, “There are many misperceptions about the potency of Zohydro in the press.” The FDA has been trying to correct those.

In an April 3 interview with TIME magazine, FDA Commissioner Margaret Hamburg, said, “It’s been said that Zohydro is super-potent. That surprises me because the highest dosage unit of Zohydro extended release is lower than the highest dosage unit of all the other available extended release products on a milligram basis…No doubt it’s a powerful drug, and it needs to be used appropriately with the proper oversight. But it’s certainly not the most powerful drug on the marketplace.”

As FDA spokeswoman Walsh explained in her email, “The highest Zohydro strength is five times the highest combination immediate-release hydrocodone strength; whereas the media is reporting 10 times…[the] highest strength of Zohydro is roughly half that of the highest strength OxyContin and extended-release morphines. Media reports have said that hydrocodone is stronger than anything on the market.”

In its own press release, Zogenix notes that a patient taking the 10-milligram Vicodin every four hours will have the same total daily dose of hydrocodone as a person taking the 30-milligram Zohydro every 12 hours. (Zohydro comes in five different doses ranging from 10 to 50 milligrams.)

A bit complicated, isn’t it? But that very complexity is all the more reason to think drug policy questions through carefully and to not rush to panicky, band-aid solutions such as banning certain drugs and not others.

Zohydro is certainly not a perfect pain drug. But it’s probably not the menace it’s portrayed to be, either.

Longtime nationally syndicated health columnist Judy Foreman is the author of “A Nation in Pain — Healing Our Biggest Health Problem.”

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  • The Moderate

    Extended-release opioids pose a health risk and restrictions on their use are warranted. The concern about Zohydro’s safe use are legitimate but the rhetoric is scientifically inaccurate and illogical. Anyone today can get a prescription for 30-mg pills of immediate-release oxycodone (Roxicodone). The health risk with this pill is identical to the health risk of Zohydro. Abuse-deterrent technologies are important, but imperfect, and the data are still out on their effectiveness. Exalgo is an extended-release, non-abuse deterrent opioid currently available as a 32-mg pill. Exalgo (hydromorphone) is 4 times more potent than hydrocodone. Opana ER (extended-release oxymorphone) was developed by Endo with abuse-deterrent technology. FDA found deficiencies in the formulation, which was one reason why they refused to pull the original New Drug Application for Opana ER, which paved the way for generic competition. As a result, you can now get generic non-abuse-deterrent extended-release oxymorphone easily. Oxymorphone is 3 times more potent than hydrocodone. I would have more sympathy for the Zohydro armageddonists if they showed similar zeal for generic immediate-release oxycodone, Opana ER, generic extended-release oxymorphone, and Exalgo. Zohydro has met the same safety and efficacy standard of Exalgo and Opana ER. If Zohydro should go, so should they, as well as generic immediate-release oxycodone. Abuse-deterrent technologies also won’t solve the problem of abuse via oral ingestion, and they won’t prevent the tragedies of opioid-naive kids ingesting these pills whole at parties and dying because of it. Remember that there are pharma companies touting abuse-deterrent technologies as the savior of medicine, and that they too have a vested interest in your believing they are telling the truth. In the mid-1990s, OxyContin was going to be “abuse resistant” because of its pharmacokinetics. That assumption was tragically wrong. The issue of safe use of extended-release opioids goes way beyond Zohydro, and the solution is far from simple.

    • davidbecker2

      You forget that opioids are not proven to be effective in the long term. Moreover opioids arent use to cure -pain but to foster a dependence on a suboptimal treatment with a long list of side effects including depression, neurotoxicity, qt syndrome sleep apnea, endocrinopathies. The sad truth is opioids might be used like ketamine to prevent or reverse wind up but they are not. But while the opioid economy wants us to focus more on opioids- that focus takes us away from discussions of better treatments for pain.

      • The Moderate

        You’ll get no argument from me about the need for new nonopioid pain relievers. The argument against long-term efficacy is true of any therapeutic. Controlled clinical trials can only be conducted so long before patients drop out or are lost to followup. The adverse effects of opioids are well known and, when combined with risk of addiction, argue for limited use of opioids. I believe patients with severe pain need them, and I think they are overused for moderate and in many cases mild pain. Good pain management takes time and should be done by a specialist. Risk assessment and patient monitoring are essential but rarely implemented adequately. Pain specialists are few and far between and dropping out of the field. It may take a patient 3 months to get an appointment with a pain specialist. Bad pain management is very easy. Write the script and forget about it. In the absence of a full withdrawal of all opioids that carry the same risk (as I mentioned above), I believe Zohydro, given the scrutiny its under, will be marketed and used more responsibly than, say, immediate-release oxycodone (Roxicodone), which is generic and has no oversight, or even Opana ER, which is “abuse deterrent” in name only. Fixing this requires a substantial rethinking of pain policy, or a new class of pain relievers that make opioids obsolete. Opioids are the 21st century version of arsenic for syphyllis. Yes, they work, but at a cost.

  • Lawrence

    Anyone notice the obvious? It’s the drug companies that brought the law suit. Not the people who use it, or the Drs.

    It’s about money. It’s about BIg Pharm upset that they won’t make the millions, with little regard of the social problems it is causing.

    Oh and to answer her question on why the FDA allowed a non-abuse-deterrent form of Zohydro on the marke?? Because if you look closely at who makes up the FDA, it’s the lawyers from the drug companies themselves.

  • Argentus

    Zohydro is incredibly similar to Oxycontin, except that it’s less well known and less abused. That, and Oxycontin makes me itchy and gives me the hiccups. It would have been nice to be able to get Zohydro after my recent surgery, but the doctor was hesitant to prescribe it, because of Deval Patrick’s purely political move to ban it.

    A couple facts: 1) People that want to get high will do so, be it with opioids, cough medicine, aerosol cans… End of story. 2) Opioids are *not* addictive if they are only used in dosages that dull the pain. Yes, you read that right. It’s neurologically impossible to get addicted to opioids unless you use them past the point of pain relief.

    So, legal, well-informed use of Zohydro by patients in real pain will never become a drug problem. This should be a non-issue.

    • Jay Starkweather

      You are incorrect on many levels. Zohydro would not have been any better for you than Oxycontin. Itchiness is a side effect of all opioids and the stronger the pill the more you will feel itchy and flush. Opioids are extremely addictive, I think the state of our prescription abuse in the United States speaks volumes. Sure, if you had a knee replacement and the doc gives you a script for a few weeks are you going to be an addict? NO. BUT if you are a “chronic pain sufferer” and have a long standing script you sure as hell are going to get addicted. Even if you are taking the pills as directed. So, legal, well-informed use of Zohydro by patients in real pain will never become a drug problem? Yeah. In a perfect world buddy.

      • Argentus

        Actually, you are incorrect. I was put on vicoprofen (same active ingredient as zohydro, just with ibuprofen, so taking larger doses is toxic), and it does not make me itch. Funny how you assume you know how my body responds to drugs, though.

        And, again, it is a FACT that opioids are NOT addictive if the person taking them only uses them to mitigate pain and not go past that point. That is a simple neurological fact. (And yes, a script for a few weeks can make you an addict, if you abuse it, contrary to what you state.)

        And… because of that last paragraph, I stand by my statement that legal, well informed use by patients in real pain won’t lead to a drug problem. Will some people use drugs incorrectly, illegally, against how they were informed? Yes. Is that a reason to deny someone else that truly needs the relief from pain that said drug could give them? No. No it isn’t.

  • davidbecker2

    Zohydro- like most other opioids lacks an evidence base for long term use. Not to mention it can cause depression, obesity, opioid induced neurotoxicity, neural tube defects, sleep apnea, hyperalgesia, QT syndrome, and lower immunity. We don’t need new and improved opioids -we need doctors using less opioids for pain. Doctors need education in pain care so they will make intelligent use of all available treatments for opioids. The fact that both the fda and zogeniz were so impolitic as to not make zohydro abuse deterrent-is proof positive they were clueless about the backlash they are now receiving. No more new opioids! Opioids are not part of the solution to pain-they are part of the problem.

    • Kevin Gorman

      “Doctors need education in pain care so they will make intelligent use of all available treatments for opioids.”

      No argument there. My believe is that opioids shouldn’t be the first ‘go to’ but rather a last resort if all else fails.

      Current abuse-deterrent technologies are largely ineffective. Zogenix has been pursuing 2 abuse-deterrent streams with technologies that look promising to be better (yet to be proven) than those currently on the market. This isn’t a new direction but has been in the works for some time. I’m sure they could have pushed forward and licensed an ineffective abuse-deterrent technology but optioned not to do so.

      98% of extended and immediate release opioids on the market today do not have an abuse deterrent, so in a sense you are correct in that they may have been surprised. They may have expected fair treatment.

      • davidbecker2

        Abuse deterrent features maybe ineffective not by accident but by intention. Experts in health care don’t like anyone telling them what to do- including government. So the makers of opioids-burdened as they are with regulatory hurdles probably balked at calls for creating abuse deterrent formulations.
        With 230 million opioid prescriptions in 2013 -obviously opioids are not used as a last resort-but as the first choice by ignorant and uncaring doctors.
        Lets talk about fair treatment- who cares about people in pain having the benefit of doctors educated in pain care and using elctrotherapies, acupuncture, ultrasound, ESWT, diet, bodymind treatments for pain. It is clear doctors are morally and mentally lazy and treat people unfairly-and we are all paying the price for that.

        • Kevin Gorman

          Abuse deterrents.. very possible and I suspect some companies have taken that road. The biggest regulatory hurdle for any medication or treatment will be at the state level if determined that each state can self regulate. There will be little if not no incentive for R&D and development or new treatments, if the requirement is to conform to an unknown standard as per the state.

          Agreed. Patient care is only as good as the doctor and their knowledge and willingness to pursue other potentially as effective treatments. Good points.

          • davidbecker2

            Dr Virchow said there are two causes of disease-pathological and political- the poisonous enthusiasm for opioids is false consciousness- a figment of the opioid economy. States have succumbed to the health care industrys moral and mental laziness in pain care by allowing doctors to do as they please and prescribe opioids as much as they please. Only when the costs of pain care were revealed in 2011 did the government start to be concerned about pain care. And so government like the health care industry is not concerned with people in pain per se- but the costs of pain care- and so again politics controls pain care. We have a capitalistic pain care system with both government and the health care industry claiming to serve the best interests of people in pain- but what they really care about is the money.

    • Laura Aly Johnson

      I’m really curious about something… Are any of you chronic pain sufferers? Because I am thanks to a failed back surgery, permanent nerve damage, fibromyalgia, among other problems. I have had facet injections, epidurals, nerve blocks, neurostimulator, biofeedback etc…nothing worked so my doctor and I turned to narcotics. Hydrocodone, Oxycodone, Morphine, Lyrica etc the “additives” in the hydro and oxy are the reason that I can’t take the dosage that may actually help so the fact that this New med is without it is awesome!!! Maybe those of use with real pain will get some kind of relief from it. Only someone who does not have severe, debilitating chronic pain would say that no new opioids are needed, that’s crap!!!!

      • davidbecker2

        Laura- the fact that you have chronic pain doesnt make you an expert on pain treatments. I too had chronic pain- for 4 years- and unlike you didnt use narcotics. If you wish to promote the use of opioids for pain making the claim that no one understands the needs of people in pain for opioids is a poor argument. For one you cant say you have tried all treatments for pain and so you cant say opioids are the only effective treatment for pain- in fact in clinical trials of opioids it is typical tat 45% dropout of the trial due to side effects and lack of effectiveness of opioids. With te exception of tramadol for some neuropathic pain most opioids lack evidence of long term effectiveness. Your list of treatments you tried is small and “biofeedback”- which type.- temp, emg, hrv? Facet injections- where ? neurostimulator- which type? Moreover, opioids treat the sensation of pain and unlike most other treatmets including marijuana get to some of the cause of the pain. As someone who had fibro for 4 years i wouldnt waste my time on an opioid- fibro is a metabolic condition and opioids would make things worse in the long run. Its your choice if you wish to take opioids indefinately- id rather keep searching for more curative/regenerative treatment if i had pain-for opioids will never cure fibro nor fbss.

        • Laura Aly Johnson

          I spent 2.5 years exploring every possible option for pain relief… At this point I would have to drag out my file to list each one, I went to 5 different specialists to avoid narcotics. At this point there is nothing that the doctors know of that will “cure” either fubto or perm nerve damage. So yes I chose to tale narcotics so I am not completely miserable everyday. It does not mean that I do not still try and find new and and better ways yo treat my problems. But I also know the limitations and side effects of current opiods are why a great many chronic pain sufferers do not get any relief. So if they can come up with am opioid or amy friggin pill or therapy that would allow us to once again enjoy life, or at least tolerate it than I am all for it

          • davidbecker2

            I recognize the great difficulty that chronic pain for it is a reflection of societal nescience- the moral and mental laziness of government and the health care industry- that continues despite all the press that poor pain care receives. Im sure you explored a lot of options- but there are many more- Mickel, manaka acupuncture, old ten needles, laserpuncture, Perrin technique, primal reflex release technique, noesitherapy, chios, higher brain living, long fasts, guafenesin, biotherapy, LENS neurofeedback, Neurofield, smr neurofeedback, ilf neurofeedback, Neuroptimal, DBS, CES, transcranial magnetic stimulation, biomodulator, biomagnetic pair, domincic method, malic acid, quintons marine plasma, reems biological theory of ionization, d- ribose, atp, quinone, homotoxicology, matrix regeneration therapy, Havening, snapping technique. I mention these, only to give you more ideas about what may be of help to you. I would say also sometimes a new commitment to a spiritual cause may also be of help. I wish you better pain relief in the near future- and am confidant you can obtain it.

          • Laura Aly Johnson

            Thanks for the info…I have tried a lot of what you mentioned, some I have not but will print this out and take to my doc as for a commitment to a spiritual cause my life is now and has always been in Gods loving hands. Thanks again.

    • scotte

      You sound like you are a Dr.?Is that the case or just someone who missed their calling?I wonder……..,Will look forward to your next post.!

      • davidbecker2

        If i were a doctor- i wouldnt know much about opioids or pain care or call for all doctors to have education in pain care. Im in fact, just a counselor.

  • Clay Jacobs

    Fairly balanced article considering most articles out there on the subject. Zohydro being singled out unfairly. Also, the Univ of Wisconsin scientist looks the most foolish. She is so perplexed by lack of ADT in Zohydro and being approved…she shouldn’t be- FDA has made it clear for a long time that ADT is not really that much of deterrent. And finally, Zogenix hasn’t made Zohydro out to be this wonder drug. Zogenix has just said it is a good option to have in the toolbox of pain doctors as it has a uniquie profile. And doubly final, don’t assume Purdue’s hydro only pill will ever get approved…not that easy and they are trying to have a 24 hour formula which further complicates their approval.

    • Kevin Gorman

      From what I have read Purdue is also porting over the same abuse-deterrent used in OxyContin. A quick youtube search (oxycontin microwave) shows the deterrent can be circumvented in 5-8 minutes? Hardly effective. Given they have a 120mg highest dosage, with questionable deterrent the media will have a field day 10x that of Zohydro. (or at least they should). Considering Purdue’s history of keeping a list of reckless doctors and not sharing with authorities, and the 634M paid in fines for misrepresenting the addictive nature of Oxycontin, I would think the public would welcome stricter regulations and oversight of Zohydro. I am still not convinced the Zohydro witch hunt hasn’t been funded by Purdue or other large competitor.

      • Steven

        These large pharma companies are slapping the Abuse Resistant Technology (ART) or Abuse Deterrent Technology (ADT) on these drugs but they are not ART or ADT at all. It would be great if companies who are creating antagonist chemistry-based approaches were fast tracked by the FDA. They just can’t compete with big pharma. I was just reading about a small pharma company in NY or NJ called Elite Pharma. Here is an example of a small pharma company which has game changing technology to curb opioid abuse by using naltrexone as an antagonist with an opioid so that if someone crushes etc., the opioid is rendered useless. Nice diagram of the compound and tech here: http://www.elitepharma.com/How_AR_Tech_Works.pdf

        • The Moderate

          The antagonist approach is viable and can be successfully brought to market by a small company, though not without some help. (Alpharma did it with EMBEDA, which is an extended-release morphine with naltrexone). It was pulled from the market due to stability issues.) Late in the development game Alpharma was sold to King, which brought EMBEDA to market. King was bought by Pfizer, where EMBEDA now languishes in oblivion. The problem with antagonists is precipitating opioid withdrawal, but that likely can be managed.