Abuse-Deterrent Opioid Analgesics: A Guide for Clinicians

Figures & data

Figure 1. FDA-recommended premarket and postmarket studies of abuse-deterrent technologies.

PK: Pharmacokinetic.

Figure 2. Abuse-deterrence claims in Section 9.2 of FDA-approved prescribing information.

Table 1. Abuse-deterrence claims in prescribing information for commercially available opioid analgesics.

Brand name (manufacturer)^‡	Active moiety	Abuse-deterrence claims in US prescribing information^†			Published reports^§	Ref.
		In vitro (category 1)	In vivo PK (category 2)	HAP studies (category 3)
Hydrocodone
Hysingla^® ER (Purdue Pharma)	Hydrocodone bitartrate	Physical and chemical properties expected to deter intranasal and IV abuse		Expected to reduce intranasal abuse and oral abuse when chewed	Harris et al. (2016) Harris et al. (2017)	[18,34,35]
Morphine
MorphaBond™ ER (Daiichi Sankyo)	Morphine sulfate	Physiochemical properties expected to make abuse via injection difficult		Expected to reduce abuse by the intranasal route	DiFalco et al. (2014) Bianchi et al. (2014) Kinzler et al. (2019) Webster et al. (2017) Webster et al. (2018)	[19,36–40]
Oxycodone
OxyContin^® ER (Purdue Pharma)	Oxycodone	Physiochemical properties expected to make abuse via injection difficult		Expected to reduce abuse by the intranasal route	Perrino et al. (2013) Harris et al. (2014)	[20,41,42]
Xtampza^® ER (Collegium Pharmaceutical, Inc.)	Oxycodone	Physiochemical properties expected to make abuse via injection difficult	Lack of dose dumping, with no increase in oxycodone levels when crushed or chewed compared with intact Xtampza ER	Expected to reduce abuse via the oral and intranasal routes	Kopecky et al. (2014) Gudin et al. (2015) Fleming et al. (2016) Brennan et al. (2017) Mayock et al. (2017) Webster et al. (2016) Kopecky et al. (2017) Meske et al. (2018)	[21,43–50]

Bold text is used to emphasize information regarding abuse deterrence.

† This information can be found in the summary at the end of section 9.2 (Abuse) in the product labeling for each opioid brand presented.

‡ Some ER opioid analgesics with abuse-deterrent labeling were never marketed or have been discontinued, including products containing morphine sulfate (Arymo^® ER, Egalet US Inc., PA, USA; Embeda^®, Pfizer, NY, USA), hydrocodone (Vantrela™ ER, Cephalon, Inc., PA, USA), oxycodone (Targiniq™ ER, Purdue Pharma L.P., CT, USA; Troxyca^® ER, Pfizer Inc) and oxymorphone (Opana^® ER, Endo Pharmaceuticals Inc., PA, USA). For products without abuse-deterrent labeling, data from abuse potential studies may be included in the prescribing information but are not followed by abuse-deterrence claims.

§ Published reports represent a subset of the data obtained from category 1–3 studies and submitted to the FDA.

ER: Extended release; HAP: Human abuse potential; IV: Intravenous; PK: Pharmacokinetic.

Hysingla™ ER (hydrocodone bitartrate) extended-release tablets, for oral use, CII, package insert . Purdue Pharma L.P, CT, USA (2018).

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Harris SC , CiprianoA , ColucciSVet al. Intranasal abuse potential, pharmacokinetics, and safety of once-daily, single-entity, extended-release hydrocodone (HYD) in recreational opioid users. Pain Med.17(5), 820–831 (2016).

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Harris SC , CiprianoA , ColucciSVet al. Oral abuse potential, pharmacokinetics, and safety of once-daily, single-entity, extended-release hydrocodone (HYD) in recreational opioid users. Pain Med.18(7), 1278–1291 (2017).

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MorphaBond™ ER (morphine sulfate) extended-release tablets, for oral use CII, package insert . Daiichi Sankyo, Inc, NJ, USA (2018).

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OxyContin® (oxycodone hydrochloride) extended-release tablets, for oral use, CII, package insert . Purdue Pharma L.P, CT, USA (2018).

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Perrino PJ , ColucciSV , ApseloffG , HarrisSC. Pharmacokinetics, tolerability, and safety of intranasal administration of reformulated OxyContin® tablets compared with original OxyContin® tablets in healthy adults. Clin. Drug Investig.33(6), 441–449 (2013).

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Harris SC , PerrinoPJ , SmithIet al. Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users. J. Clin. Pharmacol.54(4), 468–477 (2014).

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Xtampza® ER (oxycodone) extended-release capsules, for oral use, CII, package insert . Patheon Pharmaceuticals, OH, USA (2018).

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