In its latest move to curb the prescription opioid abuse epidemic, the FDA wants drugmakers to provide educational programs about managing pain and responsible ways of using opioids to doctors and other healthcare professionals.
FDA Commissioner Scott Gottlieb, speaking Monday at the start of a 2-day meeting on the impact of abuse-resistant opioids, said that the training would apply to immediate-release opioids, which account for 90% of the 200 million opioid prescriptions he says are written each year. Most of the opioids that have abuse-deterrent properties — which make them difficult to inject or snort — are extended-release versions.
“The new training will be aimed at making sure providers who write prescriptions for the IR opioids are doing so for properly indicated patients, and under appropriate clinical circumstances,” he said. He added that the training would also look at non-pharmacological methods and non-opioid drugs to deal with pain.
Gottlieb also said the FDA will survey physicians to find out their views on abuse-deterrent opioids, since he is concerned many of them may mistakenly believe that these drugs are somehow less likely to lead to addiction. “Patients can still become addicted to opioid products with abuse-deterrent features,” he noted.
In an interview with NBC News, Gottlieb said that opioid prescriptions should be written for a shorter period of time. “I believe there are still too many 30-day prescriptions being written for conditions like dental procedures or minor surgery, which should require very short-term use, if they require an opioid prescription at all,” he told the network.
The FDA meeting follows last week’s announcement from Endo International that it will comply with the agency’s request to remove its extended-release, abuse-deterrent opioid, Opana ER, from the market.
Slightly more than half of all of the opioid prescriptions written each year are given to people with mood disorders, depression and anxiety, a troubling statistic since those with mental illness face a higher risk of overdose and abuse.
About 115 million opioids prescriptions are given each year, and 51.4% of them went to people who also had a mental health disorder, according to research published in the Journal of the American Board of Family Medicine. Opioid use was defined as patients that received 2 or more opioid prescriptions in a year.
Results also showed that 18.7% of adults with a mental illness are given opioids. But just 5% of adults without a mental disorder are prescribed one.
As to why those with mental illness are more likely to receive an opioid, there are several potential reasons. Study co-author Brian Sites, MD, of the Dartmouth-Hitchcock Medical Center, told STAT that some physicians may be sympathetic to patients who have both a mental illness and another condition, making them more likely to prescribe an opioid. Also, people with mood disorders may experience pain differently. He also noted that opioids may have antidepressant effects in the short-term, prompting those with depression to ask their doctor for a prescription.
“The high prevalence of mental health disorders coupled with prescription opioid use suggests that this population is critical to consider when addressing the issue of opioid use from a health system or policy perspective,” the study authors wrote.
The FDA’s announcement last week that it wants Opana ER (oxymorphone), a powerful prescription opioid, pulled from the market has put painkiller abuse back in the spotlight. While writing up a story on the breaking news, I Iearned that the drug was reformulated back in 2013 into an “abuse deterrent” formulation (ADF). The tablets had a special coating so that if they were crushed, they would turn into a gel that would make it difficult to snort.
Needless to say, those safeguards weren’t sufficient, as evidenced by the many cases of people finding ways to still abuse the drug, which factored into the FDA’s decision. In fact, the agency previously said the reformulation may have actually made it easier to inject Opana ER intravenously, which is how the drug is primarily abused.
Despite Opana ER’s apparent abuse-deterrence failure, a number of other opioids on the market actually have that claim on their labeling. Many of those manufacturers have touted it as a way to demonstrate their apparent commitment to stop opioid abuse. It also allows them to sell the drugs at a higher price than other generic versions. (There are no generic versions of ADFs.)
So I wondered, might these other abuse-deterrent opioids not really live up to their name? After all, some of these drugs, like OxyContin (oxycodone), are heavily prescribed. As pharmacist Jeffrey Fudin wrote in a piece for Pharmacy Times, a quick Internet search he conducted found links to pages on how to undermine the abuse-resistant coating OxyContin contains.
No Protection Against Abuse From Ingestion
It’s also important to note that none of these drugs prevent another form of abuse – ingestion, by taking more or higher doses than prescribed orally – even though this is the most common way opioids are misused. Another problem is that too many doctors think these ADFs are less addictive than others. This may lead some doctors to overprescribe opioids.
A draft version of a report released last month by the non-profit Institute for Clinical and Economic Review (ICER) appears to confirm that the benefits of opioids in an ADF are not as big as some might think. In fact, they gave these ADFs a grade of C+ in terms of their ability to curb abuse. Although there has been a decline in OxyContin abuse since that product was reformulated, the ICER report found that as a result, abuse of other opioids increased. The group added that current version of OxyContin “may have limited impact on changing overall abuse problems.”
A new report gave abuse-deterrent formulations of opioids a grade of C+ in regards to their ability to curb abuse.
The fact of the matter is that abuse-deterrent opioids will do little to curb the epidemic currently ravaging our country. Although they make it harder to abuse, it is not impossible to do so. “In summary, abuse-deterrent opioids are not the panacea for opioid addiction that their title might suggest, given their increased cost compared to other formulations, the fact that they are not fully abuse-resistant and can be abused orally,” a New Jersey state advisory committee stated in a report released in January. The panel also warned the ADFs may cause some opioid addicts to turn to heroin and fentanyl to feed their habit.
The FDA seems to be taking notice that ADFs may not be as useful as thought. On June 13, FDA Commissioner Scott Gottlieb announced a 2-day public meeting on July 10 and 11 to discuss whether ADFs are indeed limiting abuse and what impact overall they are having on the epidemic.
Limit Use of Opioids Altogether To Curb Abuse
So, what do we do to stem the epidemic? It will need to come from a multifaceted approach. But the role of ADFs of opioids in achieving that goal has been largely overstated.
One of the best ways to tackle opioid abuse is to stem the prescribing of the drugs altogether. Studies have not demonstrated that opioids are more effective in relieving pain compared to non-opioid pain medications and nonpharmacological treatments. Also, opioids are associated with a host of cardiovascular, respiratory and gastrointestinal side effects, among others. Perhaps this is why last year, the Centers for Disease Control and Prevention came out with new opioid prescribing guidelines that call for the use of opioids only after other alternatives have been pursued.
It’s also important for doctors to realize the limits of ADFs of opioids. I was happy to read an opinion piece from William C. Becker, MD, and David A. Fiellin, MD, both of the Yale School of Medicine, in a recent issue of the New England Journal of Medicine, where they wrote that “clinicians, researchers, and policymakers should invest in alternative chronic-pain treatments and models of care.” That is sure to have a bigger impact on opioid use and abuse than abuse-deterrent opioids ever could.
Praise for Congress is a rarity nowadays. But members do deserve thanks for doing something this week that has the potential to benefit millions of Americans: Boosting funding for the National Institutes of Health.
Under a spending deal brokered Sunday night, the NIH will get $2 billion more in fiscal year 2017 than it did in fiscal 2016. If that sounds like a lot more money, it’s because it is.
Appropriate funding of the NIH is critical to ensure research is continued that can lead to medical breakthroughs. One of the biggest beneficiaries of the additional money is Alzheimer’s disease research. There are currently no drugs that can prevent the spread of the memory-robbing disease – current medications only treat symptoms – so the extra $400 million towards research in this area will be well spent.
The National Cancer Institute is getting a boost of almost $600 million for research. New cancer treatments are critical as many of the therapies available today only marginally improve survival and come with a host of side effects.
The additional money for health doesn’t stop with the NIH. The bipartisan deal also includes $801 million to combat opioid abuse, a whopping 430% increase compared to what was appropriated in fiscal 2016. These funds will be split between the Centers for Disease Control and Prevention (CDC), Substance Abuse and Mental Health Services Administration (SAMHSA), and Health Resources and Services Administration (HRSA).
Fighting the Opioid Epidemic
As regular visitors to MedShadow are aware, the US is in the middle of an opioid epidemic, caused in large part to abuse of prescription opioid drugs. Sales of prescription opioids quadrupled between 1999 and 2014, according to the CDC. And during that period, more than 165,000 lives were lost due to prescription opioid abuse.
Opioid abuse programs run by the CDC, treatment and overdose reversal programs at SAMHSA and treatment and prevention programs run by community health centers will all benefit from millions more in funding.
While the spending bill is certainly something to applaud, the celebration may be short lived. The bill only funds these and other government programs through the end of September. Funding beyond that is still up in the air.
Given that President Trump’s proposed 2018 budget calls for slashing the NIH’s budget by $6 billion – about 20% of its current annual budget – Congress will again have an important decision to make. Let’s hope they again muster the courage to do what is right and keep funding for critical health and medical research and programs intact.
States that passed laws legalizing the use of marijuana for medical purposes saw a bigger increase in illegal marijuana use as well a higher rate of cannabis dependence compared to states without such laws.
Researchers examined data from 3 national health-related national surveys involving more than 118,000 adults. Between 1999 and 2013, illicit cannabis use increased 1.4 percentage points more and cannabis-use disorders 0.7 percentage points more in states that passed medical marijuana laws compared to those without the laws, they reported in JAMA Psychiatry.
“A prudent interpretation of our results is that professionals and the public should be educated on risks of cannabis use and benefits of treatment and prevention/intervention services for cannabis disorders should be provided,” the authors conclude.
An accompanying editorial written by researchers at the National Institute on Drug Abuse noted that in recent years, the cannabis available to people is 3 to 4 times more potent than in the past. They also wrote that people with mental illness are more likely to engage in marijuana use, which in turn can exacerbate psychiatric symptoms.
In this episode, MedShadow founder Su Robotti discusses her first experience as an appointee to the FDA Drug Safety and Risk Management Advisory Committee. The Committee discussed the delivery system of a strong opioid called Opana.
Su Robotti: Hello my name is Suzanne Robotti and I’m the founder of MedShadow. And today, I’m with —
Jonathan Block: Jonathan Block and I’m the content manager here at MedShadow.
SR: I recently was appointed to the FDA’s Advisory Committee on Drug Safety and Risk Management, and Jonathan is full of questions about it.
JB: Absolutely, first of all, to start off, what was the purpose of your first meeting with the committee that you just were at in Washington, DC?
SR: Sure. The question about the drug in front of the committee was Opana and that is a hydromorphone drug, used for pain management. It was two committees, actually, sat together. The Drug Safety and Risk Management Committee, which I’m on, and also the Analgesics Committee which is the committee on pain management. Their panel, let’s see, there are 27 of us, all together there that is combined panels, and most of the people sitting there were epidemiologists, who are doctors that focused on how diseases go through an entire society that brought concepts of disease, and also analgesics specialist, pain specialist. I, represented, I’m a consumer representative on the Drug Safety and Risk Management Committee. So my responsibility is to bring the consumer’s point of view to the table.
JB: Great. Now, our audience may not be aware that Opana is an opioid type pain killer, which has its own set of issues. More specifically, what was the purpose of this meeting in terms of what about Opana was under debate?
SR: Well, Opana was reformulated about 4 years ago, 5 years ago to add a new coating on it that would it much more difficult to crush, or to crush or press it to inject it, in an attempt to make it abuse deterrent or AD. So initially, they thought that if they put this coating on it, they would be able to add “Opana ER,” that’s extended-release, and add AD to it for its deterrent. But the post-marketing studies, of the how the drug was accepted into society, how it was used by doctors and by patients, showed that it wasn’t actually abused deterrent, but it shifted to the style of abuse, the type of abuse to the drug.
JB: Can you explain how it shifted? SR: Sure. The abuse method of choice with Opana, but before its extended-release, but before it had this coating on it, was to crush it and to either chew it and swallow it or to crush it and snort it, or abuse it nasally, as they would say. After this hard coating went on it, it was very difficult to crush, impossible to just, I think impossible to chew and crush it, and when it did crush, it turned into a gel-like substance which theoretically is more difficult to ingest. Unfortunately, what happened was that it did deter snorting Opana, but addicts quickly shifted over to working with the gel, watering into a more liquidly substance and shooting it intravenously.
JB: Wow, that sounds very dangerous. Were there any additional problems besides your still addicting drug shooting it your arm? What sort of additional problems popped up?
SR: What they did find was that Opana, and again, I should say, that the entire hearing is available on the FDA website to watch and listen to the expert testimony and the doctors’ comments on it. So, my comments here are really what my impressions, my recollections and mu understanding was on, not on a medical expert. So having sat on this committee, I think I can say with clarity that the difference between snorting a drug and injecting a drug is the needle stick into the skin because Opana tends to be a quick-acting drug when broken in the extended release method and crush it and liquidated it. It’s a quick high that it goes down fast. So that those who are truly addicted to it, and that having to inject themselves or feeling that they have to inject themselves 3 or 4 times a day, with other skin pricks, veins start to collapse, infections starts, sepsis can set in which is very dangerous, and the transmission because of shared needles, and another reason, Hep C and HIV becomes common among these type of abuse.
JB: So what did you end up voting on, what’s the question or questions of what was the vote?
SR: The bottom question that was put in — there were several discussions questions that lead into the final vote, and the final vote was the question — does the risk of Opana ER still outweigh the benefits? Obviously, when it was first approved, the decision was, yes, the benefits outweigh to this, but I voted, at this point, it doesn’t. I, based on the information that was presented and the comments of the doctors at the table, that the risk of an intravenously abused drugs far outweighs the risks of a nasally abused drug and what one hopes, when you have an addict in the family, one hopes to keep the addict alive until somewhat rehab or program can help that addict and bring them back to a healthful lifestyle. With nasal drug abuse, that’s only going to hurt your own sinus cavity. With an intravenous drug, you get into sepsis and HIV and Hep C which just makes your company so much more difficult.
JB: So what happens at this point now that your committee and with the joint committee, now that this has happened, what happens to Opana ER? Does it get removed from the market, does the labeling have to be changed, is there some change to the labeling that the manufacturer wanted but now it won’t get? What happens now with that drug?
SR: Well, you have to go to the FDA for bringing Opana back into the table to discuss not just the AD labeling which is, you know, not something that it was ever going to happen on this case based on the studies done. But the FDA went back to discuss, really how can we move this profile from high risk to less risk. And it’s up to the FDA staff, at this point. What will ultimately happen, we are an advisory committee, the vote on the advisory committee were 18 people who agreed, who voted in the same way that I did, that the benefits no longer outweigh to the risks There are 8 people who thought that the benefits do start, and 1 person just felt that the scientific research is not strong enough to make a clear a vote on anything.
The committee chair, who is a great chair, has written up the entire proceedings and will be submitting it to the head of the FDA, for the final decision that the FDA can’t actually demand of have it be removed from the market, because they don’t have that power. However, they can change the labeling, they — to add a “black box” warning — they can recommend stronger risk management procedures, more education for doctors, pushing registration for doctors when they prescribe the drug that should be registered in a national list that other doctors know, that this patient potentially is getting multiple prescriptions for that.
So that there are things that the FDA can do, but what I think many people in the committee hope, and what I hope, was that Opana would go back to the drawing board — Endo is the company that makes it — and find a way to make this drug more safe for everybody to use because pain management is a big issue, the world is changing in pain management. It has gone way beyond just opioids, but integrating multiple [approaches] — biofeedback, physical therapy, acupuncture, other ways — so that they can be made part of the pain management profile, which is not be dependent on them alone, and be a stronger and better drug.
JB: Great, Sue. That was at least to me, a very interesting description and accounts of your meeting, thank you so much for sharing it with me, and of course with our MedShadow audience.
SR: I did write a blog on this experience, if you like to look at it, it’s at our website, www.medshadow.org.
More than 400 pages of medical research, 11 hours of testimony and a blizzard in March. Welcome to my first FDA Advisory hearing!
I am the newly appointed consumer representative on the Drug Safety and Risk Management Advisory Committee for the FDA. On March 13 and 14, our committee was joined with a sister committee. Anesthetic and Analgesic Drug Products, to determine if, based on new postmarketing research, the benefits of Opana ER, an opioid pain med, still outweigh its risks.
About a week before the meeting, 4 CDs arrived at my house so I had to clear my calendar to focus on reading medical reports. This was by far the most difficult part. As a consumer rep, I’m not expected to be trained in the technical scientific aspects, but am expected to be able to understand most of it. Frankly, I started my own cheat sheet of acronyms and key phrases: PMR = Post Marketing Requirements; PROMAQ = Prescription Opioid Misuse and Abuse Questionnaire; ETASU = Elements to Assure Safe Use; PWID = People Who Inject Drugs and too many others!
Opana ER is oxymorphone. It’s indicated for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Opana ER was reformulated in 2012 to add a substance, POI, that made the pill hard to break and, if it was successfully crushed, to turn into a gel. The company’s goal was to stop abusers from crushing and snorting Opana. The postmarketing research indicated that they were successful. Nasal abuse went down dramatically. However, clever drug abusers figured out how to liquefy the gel and shoot up. Instead, intravenous use increased dramatically.
There were many aspects to be considered, not the least of which is the very research upon which we had to make our decision. It was not of great quality.
There were many aspects to be considered, not the least of which is the very research upon which we had to make our decision. It was not of great quality. As one of my co-panelists noted, “This is a hidden population.” They are hard to study and to compare to non-abusing people.
I found the increase in IV use disturbing. Because of the unique properties of Opana ER, those addicted need to shoot up several times a day and multiple skin pricks from needles make sepsis a health hazard. Because of the high street price and the power of the drug, addicts can share one pill with 4 other users. The rate of needle sharing is particularly high with this drug and the rates of HIV and hepatitis correspondingly high.
Counterbalancing the abuse was the fact that Opana is an effective pain killer. Several committee members noted that oxymorphone is not the first choice of pain medication, but when other meds weren’t effective, they were glad to have it as an alternative. There are many patients who are able to use it without abusing it.
The question posed to us, “Do the benefits of Opana ER still outweigh the risks?” was challenging. The discussion with the committee members before the vote brought in multiple points of view which strongly informed my vote.
In my experience, a family with an addict lives in fear that the addiction will kill before the family can get the addict into a program or whatever is needed to restore health. The move from nasal to IV abuse leads to many more complications that might make recovery insurmountable, and certainly more difficult. My vote, that the benefits no longer outweigh the risks, was in the majority. Eighteen members of the panel voted as I did, 8 voted that the benefits outweighed the risks and 1 abstained.