Abuse-Deterrent Formulations: One Tool in the Opioid-Abuse Epidemic

The tentacles of prescription opioid abuse and addiction reach far. Consider Rockcastle County, Kentucky, which has a population of slightly more than 16,000 people: One person dies each week from a drug-related overdose, on average. The entire state is in crisis, with the 2010 census showing that more than 86,000 children in Kentucky are raised by someone other than a biological parent. Subsequently, “Parents’ Day” at schools is now called “Guardians’ Day.”¹ Tennessee also reports extremely high rates of termination of parental rights.² The creation of a generation of “opioid orphans” joins other obvious reasons the United States needs to address the epidemic aggressively.

In 2016, nearly 2.6 million individuals were addicted to prescription opioids or heroin. Nearly 66% of the approximately 52,000 lethal drug overdoses in 2015 were related to prescription pain relievers or heroin.³ Other data are frequent fodder for the nightly news: statistics about child abuse, domestic and interpersonal violence, homicide and suicide, motor vehicle accidents, sexually transmitted disease, and teen pregnancy.⁴

Pharmacists are aware of the problem. Most interventions designed to reduce abuse and addiction target the market’s supply side: prescription drug monitoring programs (PDMPs), Medicaid lock-in programs, pain clinic laws, enhanced diversion control, and boxed label warnings.⁵ An additional supply-side approach involves abuse-deterrent formulations (ADFs), which enhance the active medication with engineered delivery mechanisms (Table 1^4,6,7).

ADFs come in a variety of different forms (Table 2^4,8). The FDA requires manufacturers to study newly developed ADFs, comparing each with the previously approved product in laboratory, pharmacokinetic, and postmarketing studies.⁴ Proponents of increased use indicate that ADFs raise the likelihood that people with legitimate needs for opioids can obtain the drugs they need. They also indicate that ADF use decreases the chance that physicians and pharmacists will face civil and criminal liability suits related to overdose-related deaths. Proponents also point out that successful ADFs reduce the likelihood that states will need to implement other, more labor-intensive monitoring interventions.

Opponents of increasing use of ADFs argue that the cost, which is higher than that of generic and nonengineered products, does not justify their use. Opponents also say that people who cannot afford the more expensive dosage forms may seek illegal drugs from the black market or switch to less costly but more dangerous drugs.^5,9 The results of one study found a higher level of oral abuse among ADF users (26%) than those using non-ADF formulations (20%).¹⁰ Study results have also shown that not all ADFs are equally effective. Some reduce abuse by insufflation but can still be injected, and patients stymied by a new formulation often migrate to heroin.^11,12 Opponents also suggest that adherent patients will bear the burden of the increased cost.^5,9 Thus, controversy surrounds ADFs.

The FDA has approved 9 ADF opioids: 5 oxycodone products, 3 morphine products, and 1 hydrocodone product.¹³ Some are no longer available—eg Targiniq (oxycodone)—or not yet commercially available, including Morphabond (morphine),¹⁴ Troxyca ER (oxycodone),¹⁵ Vantrela ER (hydrocodone),¹⁶ and RoxyBond (oxycodone)¹⁷). Six are available: OxyContin (oxycodone), ¹⁸ Embeda (morphine), ¹⁹ Hysingla ER (hydrocodone),²⁰ Xtampza ER (oxycodone),²¹ and Arymo ER (morphine).²²

MEASURING IMPACT

ADFs’ real-world impact can be assessed only in the postmarketing period. For this reason, the FDA requires manufacturers to conduct studies after drug approval and market release. It has been difficult to determine if ADFs have had significant impact. Various institutions are conducting systematic reviews, but their conclusions are weak or ambiguous. It is critical to remember that the technology focuses on just 1 aspect of drug abuse. Some patients will still take higher opioid doses than prescribed, and ADFs remain addictive.

ADF technology is new and evolving. Large, postmarketing studies comparing specific products with conventional opioids are starting to be published and indicate that nonmedical use is lower with ADFs,⁸ along with studies that look at multiple ADFs and their downstream impact.^6,11,12

Clinicians often feel caught between a rock and a hard place. On the one hand, there has been a substantial push to consider pain a fifth vital sign and medicate it appropriately, encouraging a liberal approach. On the other, increasing use of opioids has created an epidemic of abuse and addiction, suggesting that we need to be stingier. Clinicians who prescribe or dispense opioids need to be fully aware of the potential repercussions.7 One point that every clinician needs to remember is that all interventions for pain should focus on improved functional status. Any intervention that fails to do so in noncancer pain is not working.²³

CONCLUSION

The most critical thing for pharmacists to remember is that the opioid abuse problem is multifaceted. No single intervention will solve it, and ADFs are just 1 tool. The CDC has a relatively new guideline that addresses opioid use in chronic pain.²⁴ Familiarity with its content and consistent application of the recommendations can help reduce the magnitude of this epidemic. The term “abuse deterrent” does not mean “no risk for abuse.” Health care providers who prescribe and dispense opioids must use every risk-reduction strategy possible to prevent opioid abuse, addiction, and fatalities.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

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• MorphaBond [prescribing information]. Basking Ridge, NJ: Daiichi Sankyo, Inc; 2017.
• Troxyca ER [prescribing information]. New York.: Pfizer Inc; 2016.
• Vantrela ER [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA; 2017.
• RoxyBond [prescribing information]. Valley Cottage, NY: Cerovene for Inspirion Delivery Sciences LLC; 2017.
• Oxycontin [prescribing information]. Stamford, CT: Purdue Pharma LP; 2016.
• Embeda [prescribing information. New York.: Pfizer Inc; 2016.
• Hysingla ER [prescribing information]. Stamford, CT: Purdue Pharma, LP; 2016.
• Xtampza ER [prescribing information]. Cincinnati: Patheon Pharmaceuticals Inc; 2016.
• Arymo ER [prescribing information]. Wayne, PA: Egalet Corporation; 2017.
• Manchikanti L, Atluri S, Hirsch JA. The effect of abuse-deterrent extended-release oxycodone leads to inappropriate conclusions with over estimation of safety of abuse-deterrent formulations. Pain Physician. 2015;18(3):E445-6
• CDC. CDC guideline for prescribing opioids for chronic pain—United States, 2016. cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm. Published March 18, 2016. Accessed June 20, 2017.