Formulations Inteded to Deter Manipulation, Tampering, and Abuse
Also known as abuse deterrant formulations (ADFs), these medicines are generally engineered to be difficult to crush or have other aversion properties that deter consumption in ways other than intended. Pharmaceutical deterrence strategies include physical and chemical barriers, agonist/antagonist, aversion, prodrugs and new molecules, and drug delivery systems (Tables 1-2 for overview and presentation).
Notes on Terminology
The term abuse is freuently used when discussing data related to controlled substances. It refers to the intentional, non-therapeutic use of a drug product or substance,
even once, to achieve a desired psychological or physiological effect. We recognize that some language can perpetuate stigma and negative bias toward individuals with substance use disorders and create barriers to effective treatment. For example, the term abuse has been identified by NIH as having a high association with negative judgments and punishment. The term abuse is used here to describe a specific behavior that confers a risk of adverse health outcomes; it is not intended to imply moral judgment. We have retained the term because of its common usage in the field and expected use as a search term.
We also acknowledge that the term abuse deterrent formulation may imply overarching properties of clinical safety that are unsubstaniated. Misperceptions have been noted by the FDA/CDER/Office of Communications (brief report, page 885). We have retained the term because of its common usage in the field and expected use as a search term.
Detailed study overview at the full project site OpioidData.org
See FDA Guidance on evaluation of abuse-deterrent formulations for eligibility criteria for labeling.
Full list of NDCs for abuse-deterrent formulations of opioids for analytic purposes can be found here
This document was updated November 6, 2020.
Abuse-Deterrent Formulations - Approved
| Class | Drug Name | NDA# | Categories of Evidence | Intended Route of Deterrence | Documentation | Status | ER/IR | ADF Label? |
|---|---|---|---|---|---|---|---|---|
| Opioid Analgesic | OxyContin Oxycodone HCl |
22-272 | Categories 1-3, Category 4 possible | Intravenous, intranasal | Drugs@FDA: OxyContin FDA AdCom: September 10-11, 2020 OxyContin NDCs see open issue before use Original formulation NDCs OxyContin Documentation |
Active | ER | Yes |
| Opioid Analgesic | Hysingla ER Hydrocodone Bitartrate |
206627 | Intranasal & oral: Category 1, Category 3 Injection: Category 1 |
Intravenous, intranasal, oral | Drugs@FDA: Hysingla ER Hysingla NDCs Hysingla Documentation |
Active | ER | Yes |
| Opioid Analgesic | MorphaBond ER Morphine Sulfate |
206544 | Injection: Category 1 Intranasal: Category 1, Category 3 |
Intravenous, intranasal | Drugs@FDA: MorphaBond ER MorphaBond NDCs MorphaBond Documentation |
Discontinued | ER | Yes |
| Opioid Analgesic | Xtampza ER Oxycodone |
208090 | Categories 1-3 | Intravenous, intranasal, oral | Drugs@FDA: Xtampza ER FDA AdCom: September 11, 2015 Xtampza NDCs Xtampza Documentation |
Active | ER | Yes |
| Opioid Analgesic | RoxyBond Oxycodone HCl |
209777 | Categories 1-3 | Intravenous, intranasal | Drugs@FDA: RoxyBond FDA AdCom: April 5, 2017 RoxyBond Documentation |
Discontinued | IR | Yes: Intravenous, intranasal |
| Opioid Analgesic | Embeda Morphine Sulfate; Naltrexone HCl |
022321 | Oral & Intranasal: Category 1, Category 2, Category 3 | Oral, intranasal | Drugs@FDA: Embeda Embeda NDCs Original formulation NDCs Embeda Documentation |
Discontinued | ER | Yes |
| Opioid Analgesic | Arymo ER Morphine Sulfate |
208603 | Categories 1-3 | Oral, intravenous, intranasal | Drugs@FDA: Arymo ER FDA AdCom: August 4, 2016 Arymo NDCs Arymo Documentation |
Discontinued | ER | Yes: Oral, intravenous, intranasal |
| Opioid Analgesic | Targiniq Naloxone HCl; Oxycodone HCl |
205777 | Category 1, Category 3 | Intravenous, intranasal | Drugs@FDA: Targiniq Targiniq Documentation |
Discontinued | ER | Yes |
| Opioid Analgesic | Troxyca ER Naltrexone HCl; Oxycodone HCl |
207621 | Category 1, Category 2, Category 3 | Oral, intranasal | Drugs@FDA: Troxyca ER FDA AdCom: June 8, 2016 Troxyca Documentation |
Discontinued | ER | Yes:Oral, intranasal, intravenous |
| Opioid Analgesic | Vantrela ER Hydrocodone Bitartrate |
207975 | Categories 1-3 | Oral, intranasal, intravenous | Drugs@FDA: Vantrela ER FDA AdCom: June 7, 2016 Vantrela ER Documentation |
Inactive | ER | Yes: Oral, intranasal, intravenous |
Timeline
See Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse for full history. Highlights of ADF approvals and labeling changes detailed in the table below.
| Month/Year | Event |
|---|---|
| December 1995 | Original formulation of OxyContin approved by FDA |
| July 2001 | OxyContin label updated with warnings about potential for misuse and abuse |
| August 2009 | Original formulation of Embeda approved by FDA |
| April 2010 | Reformulation of OxyContin approved by FDA |
| August 2010 | Original OxyContin removed from market and Purdue commences shipping of reformulation of OxyContin |
| June 2011 | Oxecta approved by FDA (not as ADF) |
| December 2011 | New formulation of Opana ER approved by FDA |
| July 2014 | Targiniq approved by FDA, the second ER/LA opiod with FDA-approved labeling describing the product’s abuse deterrent properties |
| October 2014 | FDA approved Embeda with new labeling describing the product’s abuse deterrent properties |
| November 2014 | Hysingla ER approved by FDA with labeling describing the product’s abuse deterrent properties |
| January 2015 | Zohydro ER approved by FDA, but was not approved with labeling describing the product’s abuse deterrent properties |
| August 2015 | FDA approced OxyContin for use in certain pediatric patients |
| October 2015 | Morphabond ER approved by FDA with labeling describing the product’s abuse deterrent properties |
| April 2016 | Xtampza ER approved by FDA with labeling describing the product’s abuse deterrent properties |
| August 2016 | Toxyca ER approved by FDA with labeling describing the product’s abuse deterrent properties |
| January 2017 | Arymo ER approved by FDA with labeling describing the product’s abuse deterrent properties Vantrela ER approved by FDA with labeling describing the product’s abuse deterrent properties |
| April 2017 | Roxybond approved by FDA as first IR opioid analgesic to be approved with labeling describing the product’s abuse deterrent properties |
Abuse Deterrent Formulations - Unsuccessful Applications
| Class | Drug Name | NDA# | Categories of Evidence | Intended Route of Deterrence | Documentation | Status | ER/IR | ADF Label? |
|---|---|---|---|---|---|---|---|---|
| Opioid Analgesic | Oxaydo/Oxecta Oxycodone HCl |
202080 | Category 3 | Intranasal | Drugs@FDA: Oxaydo Oxaydo/Oxecta NDCs Oxaydo Documentation |
Active | IR | No |
| Opioid Analgesic | Oxycodone HCl ER with blue dye (Aximris XR) Oxycodone HCl |
209653 | Categories 1-3 | Oral, intravenous, intranasal | FDA AdCom: January 15, 2020 FDA AdCom: July 26, 2017 Aximris XR Documentation |
Inactive | ER | No |
| Opioid Analgesic | Opana ER Oxymorphone HCl |
201655 | Categories 1-3, with exceptions | Intranasal, intravenous | Drugs@FDA: Opana ER FDA AdCom: March 13-14, 2020 Opana Documentation |
Inactive | ER | No |
| Opioid Analgesic | Apadaz Acetaminophen; Benzhydrocodone HCl |
208653 | Categories 1-3 | Oral, intranasal, intravenous, smoking | Drugs@FDA: Apadaz FDA AdCom: May 5, 2016 Apadaz Documentation |
Inactive | IR | No |
| Opioid Analgesic | Remoxy ER Oxycodone |
22324 | Categories 1-3 | Intranasal, intravenous, smoking | FDA AdCom: June 26, 2018 Remoxy ER Documentation |
Inactive | ER | No |
| Opioid Analgesic | Avridi Oxycodone |
206830 | Categories 1-3 | Intranasal, intravenous | FDA AdCom: September 10, 2015 Avridi Documentation |
Inactive | IR | No |
| Stimulant | AR19 Amphetamine sulfate |
211179 | Categories 1-3 | Intranasal, intravenous | FDA AdCom: October 8, 2020 AR19 Documentation |
Inactive | IR | No |
| Opioid Analgesic | Acurox Oxycodone HCl; Niacin |
22-451 | Categories 1-3 | Intranasal, intravenous, oral | FDA AdCom: April 22, 2010 Acurox Documentation |
Inactive | IR | No |
Historical and Pre-market Products
Two older products in particular influenced the modern conceptualization of abuse deterrent formulations: Talwin NX and Suboxone.
Many earlier development projects did not result in products brought to market: ReXista, DETERx, OROS Hydromorphone, OxyNal, Oxytrex, etc. (Table 1, full citation) for a partial list.
We are interested in listing publicly acknowledged pharmaceutical development efforts for new products that may fall in this category.