Abuse-Deterrent Formulations: A Solution to the Problem

By | January 25, 2018

Despite continuous efforts to address the problem, high rates of prescription opioid use and abuse continue to plague our country.  According to the CDC, deaths involving prescription opioids in the United States have quadrupled since 1999, and so have the sales of these prescription drugs.  In 2015, the American Public Health Association published a policy that noted that every 19 minutes, someone in the United States dies from an unintentional prescription drug overdose.  

Prescription opioid abuse and misuse have implications not only for individual patients but also for the overall health system.  Each day, more than 1,000 people are treated in emergency departments for prescription opioid misuse.  Emergency department visits are very costly. The CDC reported early in 2017 that the U.S. spent $78.5 billion on prescription drug abuse and overdose in one year.  In fact, opioid-related hospital visits are up 99% in the last decade [pdf]. The highest rates of opioid-related inpatient hospital visits are among patients aged 25 through 44 and 45 through 64 years, whereas the highest rate of opioid-related ED visits [pdf] are among patients aged 25 through 44. Though the increase in drug-overdose deaths can be directly attributed to the use of illicit opioids, the CDC Director of the National Center for Injury Prevention and Control gave testimony that “[w]hile most people who misuse prescription opioids do not go on to use heroin, the small percentage (about four percent) who do account for a majority of people recently initiating heroin use.” [pdf]

Where do we go from here?  Patients need medications for pain management, so physicians cannot stop writing prescriptions for opioids altogether.  Last year, the CDC issued strict guidelines on prescribing opioids for chronic pain in an attempt to deter physicians from prescribing an excessive amount of opioids and to focus more on patient-centered strategies. Ways to move forward are to continue to educate physicians and patients alike of these important guidelines and to support the Food and Drug Administration as it responds to this public health crisis, especially in its attempts to expand the cutting-edge technology to address this problem.

The pharmaceutical industry has shown significant interest in developing abuse-deterrent formulations (ADFs) for opioids and the technology is progressing rapidly. The FDA issued guidance [pdf] to pharmaceutical manufacturers on the development of ADFs. The outcome of the FDA’s guidance is that it spurs innovation and generic ADF product development, which helps to increase access and affordability.

Abuse-deterrent technologies target known or expected routes of abuse relevant to the proposed product.  Because opioid products can be abused in many ways — swallowing whole, crushing and swallowing, crushing and snorting, crushing and smoking, or crushing, dissolving, and injecting — abuse-deterrent technologies can address these different forms of abuses.

  1. The physical/chemical barrier can limit drug release following mechanical manipulation, or change the physical form of a drug, rendering it less amenable to abuse. 
  2. Agonist/antagonist combinations can be added to interfere with, reduce, or defeat the euphoria associated with abuse or manipulation of the drug. 
  3. Aversion involves adding substances to the product that produce an unpleasant effect if the dosage form is manipulated or if it is used at a higher dosage than directed.  
  4. Delivery systems involving a different release designs or methods of drug delivery that can offer resistance to abuse. 
  5. New molecular entities and prodrugs, which could include the need for enzymatic activation, different receptor binding profiles, slower penetration into the central nervous system, or other novel effects (all of which are subject to evaluation of abuse potential for purposes of the Controlled Substances Act). 

Post-marketing data show that the use of opioid ADFs reduces rates of abuse without sacrificing safety or effective pain management.

While ADFs rely on cutting edge technology, and must undergo long-term epidemiological studies to assess their clinical abuse potential, there are still some drawbacks.  The idea that opioids are only capable of causing harm if they are tampered with is inaccurate and difficult to change.  

Another misconception of ADFs is that they protect people from other harms associated with opioids. Opioids can pose a myriad of problems that extend beyond abuse, including endocrine, cardiovascular, gastrointestinal, neuropsychiatric, and respiratory effects.  It is also important to note that ADFs are not abuse-proof.  Even federal regulators recognize that the emerging science in this area is challenging and ever-changing.  

To date, there are nine products with abuse-deterrent labels that have been approved by the FDA.  Those products are: OxyContin (physical/chemical barrier), Targiniq ER (agonist/antagonist), Embeda (agonist/antagonist), Hysingla ER (physical/chemical barrier), MorphaBond (physical/chemical barrier), Xtampza ER (physical/chemical barrier), Troxyca ER (agonist/antagonist), Arymo ER (physical/chemical barrier), and Vantrela ER (physical/chemical barrier).  

The future of ADFs is yet undetermined.  According to a review by several pharmacists, ADFs’ relatively high costs, coupled with uncertain insurance policies, and limited data on pharmacoeconomics, warrant collaborative monitoring and assessment by government agencies, pharmaceutical manufacturers, and data analysis services to define their therapeutic role in the future.

Despite these cautions, the development of abuse deterrents that prevent opioids from being easily abused by opioid addicts is an approach that can be implemented by the pharmaceutical industry better than any other stakeholder. Though the government and private sector often find themselves at odds, to address the opioid epidemic in this country, we are going to need to enlist the help of the CDC, the FDA, and the pharmaceutical industry. Legislators and policymakers must continue to work alongside physicians, pharmaceutical industry representatives, and lobbyists to overcome the epidemic that is sweeping our nation and needlessly taking tens of thousands of lives.

Ashley Estebo

Ashley Estebo

Ashley Estebo graduated from Westmont College in Santa Barbara, CA in 2016 with a Bachelor of Science in Biology. Presently, she works at a health care facility in Southern California and is a full-time student at George Washington University Milken Institute School of Public Health where she will earn her MPH with a focus on health policy. She will graduate from the MPH program in May 2018. Her research focuses are on health policies, health care legislation, and program development and management. She plans to apply for medical school and pursue a career as a physician who advocates for and researches policy solutions to address and promote women’s and children’s health.
Ashley Estebo
Ashley Estebo

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