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14 Articles in Volume 18, Issue #2
Ask the Expert: Is there evidence to prescribe cyclobenzaprine long-term?
Challenging the Chronic Pain Personality Profile
Designer Peptide May Prevent Chemo-Induced Neuropathy
Inside the Cancer Pain Research Consortium
Intrathecal Drug Therapy for Cancer-Related Pain
Managing Cancer Pain in an Era of Modern Oncology
Mapping Complex Pain: A Case Study
Medication Overuse Headache: Inaccurate and Overdiagnosed
Pain and Fall Risk in the Elderly
Reporting Quality of Care in Cancer Pain Management
Sharing the Risk: An Update to DEA & Doctors Working Together
The Intensifying Conflict Between Opioid Control and Pain Control
Two Mobile Apps Aim to Target Patient Compliance & Safety
Why Prescribers Need to Adopt Abuse-Deterrent Opioids

Why Prescribers Need to Adopt Abuse-Deterrent Opioids

Available and evolving abuse-deterrent technologies offer a path away from abuse, misuse, and diversion.

As states and physicians scramble to meet the CDC opioid guidelines,1 they might keep in mind that more options are available for helping to reduce opioid abuse and misuse among patients than just changing prescribing patterns. While not all abuse, misuse, and diversion can be deterred, abuse-deterrent opioids (ADOs) offer a shift away from the deadliest forms of opioid misuse – intranasal and intravenous abuse. The most serious safety events and addiction-related deaths occur via these methods, at an approximately 2.5 times greater prevalence rate than oral abuse.2

Types of Deterrent Formulations & Technologies

For the estimated 11% of adults who experience daily pain,3 as well as the millions of Americans who manage acute pain with prescription opioids, ADOs provide an additional layer of risk prevention. ADO formulations are designed to deter dose tampering, increase the time and energy required to remove extended-release capabilities, and decrease/limit the reward (ie, quick high) of the opioid. While there are a variety of abuse-deterrent formulation (ADF) approaches, there are three chief methods in use or under development that promise to address different abuse activities:

  • Physiochemical barriers: These barriers use ingredients and manufacturing technology to make the product resistant to crushing, chewing, and gelling. As a result, the tablets cannot be broken down into a powder fine enough to ingest via the nasal route, and if dissolving is attempted, then the formulation transforms into a gel-like mass, which makes it difficult to push through the needle of a typical syringe. Example: OxyContin.
  • Pharmacological barriers: It is known that opioids work by attaching themselves to receptors in the body. By embedding antagonists into the pill, the effect of the narcotic is blocked when abused (eg, when crushing or dissolving), while still releasing the appropriate medication. Example: Hysingla.
  • Prodrugs: These formulations are inactive, bioreversible derivatives of active drug molecules that must undergo an enzymatic or chemical transformation to release the parent drug, which can then elicit its desired pharmacological effect in the body. For example, when a prodrug tablet reaches the intestines, enzymes in the digestive system cause the release of the active ingredient as prescribed. Prodrugs aim to help prevent the rapid euphoria that abusers seek by disincentivizing intranasal or intravenous abuse. Example: aspirin. The first immediate-release produg with abuse-deterrent properties may soon receive FDA approval.

Table I lists the 10 currently FDA-approved abuse-deterrent opioids, some of which are still pending commercialization.

What to Expect from Abuse-Deterrent Opioids

Abuse-deterrent formulations of opioids may be the most substantive contribution to the fight against prescription drug abuse that pharmaceutical technology innovators are offering at this time. Clinicians adding these products to their treatment armamentarium, however, must align their expectations with the products’ technological capabilities. For starters, prescribers should be aware that ADF technologies are either additive to a therapeutic moiety or represent a new molecular entity (NME). The presence of an ADF within an ADO has no impact on the designed therapeutic benefit of the opioid.

While ADOs are capable of preventing abuse, they are not expected to prevent abuse of DEA scheduled products, but rather, aim to lower the abuse potential of those products. Their formulations were largely designed to target the opioid naive patient and early stage recreational abusers; the technology may not effectively deter a professional manipulator, a desperate addict, or an experienced abuser. Abuse-deterrent opioids with ADF technologies should, therefore, be considered part of a multifactorial effort to deter a patient from progressing from potential abuse, misuse, or diversion to the more lethal intranasal/intravenous forms of abuse.

Furthermore, it is important to be aware that ADOs are both equally effective and equally as dangerous as current non-ADOs. The risk of death or a severe adverse event of any opioid is unchanged by the addition of, or lack of, an abuse-deterrent formulation. There are no products on the market yet that claim to reduce abuse by swallowing – and no abuse-deterrent technology provides 100% risk protection.

Why Add ADOs to Your Armamentarium?

So why should prescribing physicians undertake the effort to deter abuse, misuse, and diversion from the oral to the more aggressive routes?

Deterring injection with prescription opioids has been a primary public health goal based on intravenous and intranasal abuse statistics associated with more severe health consequences. As noted, researchers 2 have suggested that the relative risk of death or a major adverse effect (eg, overdose) for the intravenous route is 2.6 times greater than abuse by oral route. Deterring intranasal abuse of prescription opioids yields a similar benefit, as the relative risk of death or a major adverse event for intranasal abuse is 2.2 times greater than oral abuse.3

With these statistics in mind, ADOs may help to prevent an opioid naive patient or early stage recreational abuser from potentially progressing from oral abuse (the most widely used form of abuse at 93%2) to intranasal/intravenous forms of abuse.

To date, the use of abuse-deterrent technology in practice is still in its nascent stages, representing approximately 6.6 million prescriptions out of nearly 249 million total prescriptions4 filled in the United States in 2015. These formulations represent about 2% of all opioid prescriptions. 4 Despite their slow adoption, ADFs have proven to reduce prescription drug abuse and its consequences, 5 and even an incremental reduction in abuse may have a significant impact on national healthcare by reducing the costly social, physical, mental, and public health problems that result from abuse.

While federal public policies need to encourage innovation and incentivize a market shift toward ADFs, healthcare providers have an opportunity to move forward adoption of these products by simply writing a “no-substitute” prescription for a suitable ADO when an opioid is the appropriate therapy.

As in any public health emergency, an “all of the above” policy should be pursued, utilizing all potential and available solutions. More informed prescribing, along with enhanced patient education and safeguarding, must be part of an appropriate multimodal response to this national health challenge.

FDA Targets Packaging & Labeling

As part of the FDA’s ongoing efforts to “reduce exposure to opioids,” Commissioner Scott Gottlieb, MD, stated in a late January 2018 announcement that the agency is placing more emphasis on abuse-deterrent packaging and labeling.

“We can use changes in packaging as a way to give providers better options for tailoring how much they prescribe to the clinical need,” he explained. Such changes are particularly applicable to immediate-release opioid products and those indicated for short-term use.

To start, the agency asked the manufacturer (Johnson & Johnson) of loperamide, indicated to treat short-term diarrhea and which contains opioid-based ingredients, to reduce the amount of opioid product in its distribution chain. While loperamide is safe when used at its approved doses (8 mg per day over-the-counter, and 16 mg per day prescription), the medication has reportedly been used in large quantities by drug abusers, as well as those attempting to treat opioid withdrawal symptoms, according to the FDA statement.

The product’s labeling was adjusted in spring 2017 to include a warning label regarding the ingestion of high doses. FDA has now asked the company to implement packaging limitation and unit of dose packaging changes to further deter abuse.

The agency has also asked distributors to voluntarily assist in monitoring/reducing large quantity sales of the product. “I believe anyone who is distributing healthcare products has an obligation to be a partner in helping address the most pressing public health challenges like opioid abuse,” said Dr. Gottlieb in the announcement. “You have a social contract to take voluntary steps to help address public health challenges.”

According to the agency’s statement, FDA hopes that packaging tweaks such as that being requested for loperamide may assist in reducing opioid misuse and abuse. “If more immediate-release drugs, in particular, were packaged in three or six-day blister packs; then more doctors may opt for these shorter durations of use,” said Dr. Gottlieb.

Last updated on: June 25, 2020
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Inside FDA's Guidance on Generic Abuse-Deterrent Opioids
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