Surveys Find Most Americans Not Worried About Painkiller Risks

By Pat Anson, Editor

Health officials, regulators and politicians have been warning for years about the so-called epidemic of prescription drug abuse in the U.S. But two new surveys show that most Americans are not as concerned about the abuse of pain medications and don’t want the government to restrict access to them.

A survey of over 1,000 Americans by the National Safety Council found that only 1 in 5 (19%) consider prescription pain medication a serious safety threat. Two-thirds of those taking opioids are not worried about side effects and only 12% are concerned about addiction.

The survey found broad support for opioids among those who take the medications.

• 78% believe opioids are the fastest way to treat pain.
• 71% believe opioids are the “best overall solution” for pain.
• 69% believe opioids are the “most appropriate solution” for pain.
• 52% believe opioids are safer than other pain medications.
• 42% wrongly believe it is legal to share opioids with family and friends.

"Forty-five people die every day from overdosing on prescription painkillers," said Deborah A.P. Hersman, president and CEO of the National Safety Council. "These medications are federally controlled substances and gateway drugs to heroin. Sharing drugs is never worth the risk, especially when non-addictive, over-the-counter pain relievers are often better options."

A second survey of 1,600 Americans, conducted by the non-profit Alliance for Aging Research, found an overwhelming majority opposes the government restricting access to medication that contains acetaminophen -- the world’s most widely used over-the-counter (OTC) pain reliever.

Over 50 million people in the U.S. use acetaminophen each week for pain and fever – many not knowing the medication has long been associated with liver injury and allergic reactions such as skin rash. Over 50,000 emergency room visits each year in the U.S. are blamed on acetaminophen overdoses, including 25,000 hospitalizations and 450 deaths.

The Food and Drug Administration has considered requiring a doctor’s prescription for acetaminophen products such as extra-strength Tylenol.  But the vast majority of survey participants disagree with the concept of restrictions.

• 75% of those under age 60, and 70% of respondents over age 60, believe the FDA should not require a doctor's prescription to buy extra-strength Tylenol or an equivalent store brand.
• 52% of those under age 60, and 45% over age 60, believe that requiring a prescription will make it more difficult to obtain safe pain medications.
• Only 11% of those under age 60, and 19% over age 60, would go to a doctor for a prescription for acetaminophen.
• 77% of those under age 60 and 68% of those over 60 prefer consumer education to government restriction as a way to protect people from acetaminophen overdose.

"The aging of our population means that more Americans will be faced with persistent pain," says Cynthia Bens, Vice President of Public Policy for the Alliance for Aging Research. "Potential barriers to OTC medication access may have unintended health consequences for seniors who rely on OTC pain relievers that contain acetaminophen to reduce their pain and maintain their quality of life."

The survey also offered insights into the amount of pain people experience:

• More than 18% of respondents age 60 and over have bad or severe pain, while 37% have daily pain.
• 70% of those aged 60 and over use OTC pain medication.
• For those under age 60, bad or severe pain is experienced by 15%, while 25% experience daily pain.
• 81% of those under age 60 use an OTC pain medication.

The FDA recommends taking no more than 4,000 mg of acetaminophen in a 24-hour period. In 2011 the agency asked drug makers to limit acetaminophen to 325 mg per tablet or capsule. The FDA also required a “Boxed Warning” label – the agency’s strongest warning – which is used to call attention to serious risks.

OxyContin Still Being Abused by Addicts

By Pat Anson, Editor

Drug addicts are still finding ways to snort and inject OxyContin, five years after the painkiller was reintroduced in an abuse deterrent formula.

Researchers at Washington University School of Medicine in St. Louis surveyed almost 11,000 opioid abusers at 150 drug-treatment facilities and found that over a quarter of them still abused the painkiller, even though the new formulation of OxyContin is harder to crush or liquefy. Their study is being published in JAMA Psychiatry.

The abuse-deterrent formulation of OxyContin was introduced by Purdue Pharma in 2010, at a time when the painkiller was widely being abused. Nearly half of patients entering drug treatment facilities that year for opioid abuse said they had used OxyContin to get high at least once in the previous 30 days.

Two years later, after the abuse-deterrent formulation was introduced, the percentage of opioid abusers entering rehab who used OxyContin had fallen to 26 percent.

"We found that the abuse-deterrent formulation was useful as a first line of defense. OxyContin abuse in people seeking treatment declined, but that decline slowed after a while," said senior investigator Theodore J. Cicero, PhD, a professor of neuropharmacology in psychiatry.

"The newer formulations are less attractive to abusers, but the reality is -- and our data demonstrate this quite clearly -- it's naïve to think that by making an abuse-deterrent pill we can eliminate drug abuse. There are people who will continue to use, no matter what the drug makers do, and until we focus more on why people use these drugs, we won't be able to solve this problem."

The findings are not unexpected, according to a prominent pain physician.

“No one should expect that ADF's (abuse deterrent formulations) are not going to be abused.  They will.  Some ADF's will be more effective in deterring certain methods of abuse like injecting or snorting.  People who want to abuse can just take more orally or with enough effort can overcome the ADF technology,” said Lynn R. Webster, MD, a past president of the American Academy of Pain Medicine and vice president of scientific affairs at PRA Health Sciences.

“As long as an opioid has rewarding properties a certain part of society will seek them out for abuse.  This is why we need to be realistic about what an ADF can accomplish.  We need to decrease the demand and eventually replace the type of opioids that produce liking with drugs that are not as rewarding but more effective.”   

Researchers say about a third of the addicts who still abused OxyContin had found a way to inhale or inject it. The rest took the painkiller orally. Even more worrisome, almost half of the drug abusers surveyed in 2014 reported they had used heroin in the 30 days before they entered treatment.

"Some people found ways to get around the abuse-deterrent formulation so that they could snort or inject it, and others simply swallowed the pills," Cicero explained. "But many people switched to heroin, and that's a major concern."

Cicero says 70% of the addicts who stopped using OxyContin and switched to other drugs were using heroin.

“Abuse-deterrent formulations can have the intended purpose of curtailing abuse, but the extent of their effectiveness has clear limits, resulting in a significant level of residual abuse. Consequently, although drug abuse policy should focus on limiting supplies of prescription analgesics for abuse, including ADF technology, efforts to reduce supply alone will not mitigate the opioid abuse problem in this country,” Cicero wrote in the study.

“We agree with Dr. Cicero that abuse-deterrent formulations are a valuable public health tool that must be part of any comprehensive approach to combatting prescription drug abuse. The report parallels other studies that show reformulated OxyContin is associated with a reduction in abuse,” said David Haddox, MD, V.P. of health policy at Purdue Pharma.  

“The product’s label states that OxyContin has physical and chemical properties expected to make abuse via injection difficult and to reduce abuse via snorting. The label also states that abuse of OxyContin by these routes, as well as the oral route, is still possible.”

Many pain patients with legitimate prescriptions for OxyContin say the abuse deterrent formulation is not as effective at providing pain relief as the old one. Others complain about side effects such as gastrointestinal problems.

Abuse deterrent technology is a key part of the Food and Drug Administration’s efforts at combatting the so-called epidemic of prescription drug abuse. Over 16,500 deaths in the U.S. were linked to opioids in 2010.

According to the National Institutes of Health, only about 5% of patients taking opioids as directed for a year end up with an addiction problem.

Spider Venom Could Take the Sting Out of Chronic Pain

By Pat Anson, Editor

Black widow spiders are well known for their dangerous, painful and sometimes even lethal bites. The venom of a female black widow is 15 times as toxic as a rattlesnake’s.

But that venom also contains an ingredient that could be developed into a new class of potent painkilllers.

Researchers in Australia have identified seven compounds in the venom of spiders that block the body's ability to send signals to the brain through what is called the pain pathway – also known as Nav 1.7 channels.

"A compound that blocks Nav 1.7 channels is of particular interest for us. Previous research shows indifference to pain among people who lack Nav 1.7 channels due to a naturally-occurring genetic mutation - so blocking these channels has the potential of turning off pain in people with normal pain pathways," said study leader Glenn King, PhD, of The University of Queensland's Institute for Molecular Bioscience.

King and his colleagues built a system that can rapidly analyze the protein molecules in spider venoms. They studied the venom of over 200 spider species and found that 40% of the venoms contained at least one compound that blocked human Nav 1.7 channels. Of the seven promising compounds identified so far, one is particularly potent and has a chemical structure that suggests it has a high level of chemical, thermal, and biological stability, which would be essential for administering in a new medicine.

"Untapping this natural source of new medicines brings a distinct hope of accelerating the development of a new class of painkillers that can help people who suffer from chronic pain that cannot be treated with current treatment options," said researcher Julie Kaae Klint, PhD.

Researchers have only scratched the surface. There are over 45,000 species of spiders, many of which kill their prey with venoms that contain hundreds - or even thousands - of protein molecules that block nerve activity.

"A conservative estimate indicates that there are nine million spider-venom peptides, and only 0.01% of this vast pharmacological landscape has been explored so far," says Klint.

The study is published in the British Journal of Pharmacology.

Researchers are also studying the potential of venom in cone snails for its potential for blocking pain signals in humans. German scientists at the Pharmaceutical Institute of the University of Bonn say one advantage of the peptides found in snail venom is that they decompose quickly and are unlikely to cause dependency.

A pharmaceutical drug derived from cone snail neurotoxins has already been developed and marketed under the brand name Prialt. The drug is injected in spinal cord fluid to treat severe pain caused by failed back surgery, injury, AIDS, and cancer.

New Opioid ‘Film’ Nears FDA Approval

By Pat Anson, Editor

The Food and Drug Administration has accepted a new drug application (NDA) for a new opioid film patch that could give chronic pain patients an alternative to hydrocodone and other painkillers that have become harder to get prescriptions for.

Image courtesy of biodelivery sciences

The buprenorphine film – to be sold under the brand name Belbuca -- was developed by Endo International (NASDAQ: ENDP) and BioDelivery Sciences (NASDAQ: BDSI) for the management of chronic pain requiring daily, long-term opioid treatment. The companies are hoping for final FDA approval by October, 2015.

Buprenorphine is an opioid that has long been used as an addiction treatment drug sold under the brand name Suboxone, but it can also be used to treat chronic pain.

"NDA acceptance represents an important step forward in our commitment to bringing to patients new therapeutic options for the treatment of chronic pain. We believe that Belbuca is a significant advancement in pain care, and an important extension to Endo's portfolio of products," said Rajiv De Silva, President and CEO of Endo.

Buprenorphine is a Schedule III controlled substance, meaning that it has been designated as having lower abuse potential than Schedule II drugs, a category which includes hydrocodone and most opioid painkillers. Many pain patients are having difficulty getting prescriptions for hydrocodone and other Schedule II drugs filled.

"The FDA's acceptance of our Belbuca NDA is a significant milestone for BDSI and in our partnership with Endo," said Dr. Mark Sirgo, President and CEO of BDSI. "We believe that Belbuca can offer those suffering with chronic pain with a novel treatment approach.”

Belbuca contains one-tenth to one-twentieth the amount of buprenorphine as Suboxone and other products that are used to treat opioid addiction.  Although the dose of buprenorphine is smaller, Sirgo says Belbuca film is effective in treating pain because the drug is absorbed through the inside lining of the cheek and enters the blood stream faster. In a Phase III study, he said the film was effective in treating patients who were taking a “hefty dose” of opioids equivalent to 160 mgs of morphine a day.

Belbuca is also less likely to be abused, according to Sirgo, because the patches are difficult to grind or liquefy for snorting or injecting.

Buprenorphine is already used to treat pain in transdermal skin patches made by Purdue Pharma under the brand name Butrans.

Hysingla & Zohydro: Same Church, Different Pew?

By Dr. Jeffrey Fudin

Same church different pew you ponder?  It’s not that simple. 

Almost a year to the day since the availability of Zohydro ER (hydrocodone extended release, manufactured by Zogenix), there is now another kid on the block; Hysingla ER (hydrocodone extended release, manufactured by Purdue). Nobody can deny that Zogenix paved a pretty hefty path to bring and keep this on the market.

Along the way was a pretty disheartening road.  But no matter how many unearthed faults were found in the path, they were minuscule compared to the faulted rhetoric among media sensationalists and politicians. With one road block after another, it became clear that politicians were more interested in saying something (anything) for the attention than they were about the truth. In fact, their futility and sensationalistic journalism promulgated numerous blogs here.  

On the one hand I suppose that was cultivating for this site and our readers, but unfortunately it was on the backs (perhaps literally) of legitimate pain sufferers that might otherwise benefit from an extended release formulation of hydrocodone.  Rehb.com provides some interesting infographics that break down nationally and by state, various permutations of how “Admissions to treatment facilities has been steady or rising for the past 20 years, yet it seems elected officials spend less and less of their time on the floor of the House and Senate talking about it.”

The indisputable facts are that since Zohydro ER release in March 2014, there have been over 50,000 prescriptions filled (almost 3 million capsules dispensed) yet an extremely low incidence of abuse, misuse, and diversion reported in the surveillance databases. 

Do note however that because schedule II drugs are not allowed automatic refills, each Rx is considered an initial fill, so the 50,000 prescriptions does not equate to 50,000 patients. I imagine we will see similar safety and surveillance data for Hysingla ER in the months ahead.

So, you ask, what are the differences?  On the surface it seems simple; 1 ) Hysingla ER is once daily dosing and Zohydro ER is twice daily dosing; 2 ) Hysingla ER has an FDA label as “abuse deterrent” and Zohydro ER does not (yet); and 3 ) Hysingla ER is a tablet and Zohydro ER is a capsule.

Let’s break this down, because ultimately it really should be about the patient.

History tells us that once daily or twice daily intended dosage forms sometimes require twice or three times daily dosing respectively.  Third party payers have notoriously used this as an excuse not to pay. By way of example, OxyContin (oxycodone extended release) is indicated for every 12 hour dosing, but it is not uncommon to see it appropriately prescribed every 8 hours instead of every 12 hours. The same is true for Avinza (morphine extended release).  Avinza is indicated for every 24 hour dosing, but it is not uncommon to see it prescribed every 12 hours instead of once daily. The best example where reality, practicality, and just plain good medicine flew in the face of the original package insert is brand name Duragesic, fentanyl transdermal (TD).   

The original package insert required every 72 hour changes of the patch.  Some patients didn’t receive adequate analgesia for that period of time – the manufacturer recommendation therefore was to raise the patch dosage to the next highest strength.  Sure, this would therefore raise the overall serum levels thus extending the therapeutic blood levels perhaps into the third day, but was it clinically the best thing for the patients and did it adhere to basic therapeutic principals?  The answer is no!  We always want to give the lowest effective dose.  If that could be achieved by remaining on the same fentanyl dose and changing it more frequently, then that is the proper approach.  See Medscape, Can Fentanyl Patches Be Replaced Sooner to Improve Pain Control?

To address point #1 above, the once daily practicality and convenience of Hysingla ER is of course a wonderful thing.  For a caregiver that can only get to the home once daily, it is a Godsend.  But, although it is a nice option for many, some patients might be better off on a lower overall 24 hour dose by using the every 12 hour dosage form of Zohydro ER.

To address point #2, abuse deterrent technology (ADT) is a wonderful thing too (kudos to Purdue), but ADT is not the be all and end all of substance abuse; it is simply another option.  To read more about that, see the Pharmacy Times article Abuse-Deterrent Opioid Formulations: Purpose, Practicality, and Paradigms. For the record, Zogenix ER has received FDA approval for their new abuse deterrent formulation.

And finally to address point #3, Hysingla ER is a tablet and Zohydro ER is a capsule.  From experience, it is clear that some patients are better able to swallow one compared to the other.  For some, the fear of swallowing a tablet (a form of phagophobia) is insurmountable.  For those that cannot swallow a tablet, I do prefer a capsule and the patient is told to sit or stand straight, place the capsule in their mouth, sip a mouthful of water, and look down towards the table or floor.  The capsule floats to the back of the throat – now swallow.  Although this often works, some might do better with a small tablet.

Hysingla ER is available by tablet in milligram strengths of 20, 30, 40, 60, 80, 100, and 120.

Zohydro ER is available by capsule in milligram strengths of 10, 15, 20, 30, 40, and 50.

For the benefit of media sensationalists and political mouthpieces, let me save you the trouble and embarrassment this time around, because if tempted, I will call you out publically again.  Hysingla ER 120mg is not 3 times more potent than Zohydro ER 40mg. They are equipotent because hydrocodone is hydrocodone is hydrocodone as explained in the previous post here, ZOHYDRO: What weighs more – A pound of feathers or a pound of hydrocodone?

Kudos to the two companies that fought to bring these new options to market for patients that can truly benefit from a single entity extended release dosage form of hydrocodone. 

Jeffrey Fudin, PharmD, is a Diplomate to the American Academy of Pain Management. 

Dr. Fudin practices as a Clinical Pharmacy Specialist and Director at the Stratton Veterans Administration Medical Center in Albany, NY.  

This column is republished with permission from Dr. Fudin’s blog.