DETER MORPHINE IV ABUSE WITH ARYMO® ER (MORPHINE SULFATE) EXTENDED-RELEASE TABLETS CII

When subjected to a liquid environment, manipulated ARYMO ER forms a viscous hydrogel, which resists passage through a needle for abuse by injection.2

RESISTS CHEMICAL MANIPULATION

ARYMO ER with Guardian™ Technology is formulated with inactive ingredients that make the tablet more difficult to manipulate and is expected to make abuse by injection difficult.

Abuse of ARYMO ER by injection, as well as by oral and nasal routes, is still possible.

chemical_manipulation.jpg

Manipulated ARYMO ER in a small volume of commonly used IV solvent.

ORAL HUMAN ABUSE POTENTIAL (HAP) STUDY — NONDEPENDENT RECREATIONAL OPIOID USERS

Study design

An Oral Human Abuse Potential study was conducted in 39 subjects who were nondependent recreational opioid users; 38 subjects completed the study. The pharmacokinetic profile of manipulated ARYMO ER was characterized following oral administration. The study was conducted using a randomized crossover design. All study drugs were manipulated at an onsite pharmacy using a single‑tool manipulation method. Subjects did not manipulate the medication on their own. Treatment arms included manipulated ARYMO ER 60 mg tablets (taken with juice), intact ARYMO ER 60 mg tablets (taken with juice), crushed 60 mg MS Contin® (morphine sulfate extended-release tablets) taken with juice, and placebo.2

ORAL PK DATA

chart1_mobile.png

Manipulated ARYMO ER has lower peak plasma concentration compared with crushed MS Contin®:2

  • Oral PK data demonstrated mean maximum plasma concentrations (Cmax) were lower for both intact and manipulated ARYMO ER compared with crushed MS Contin®2
  • The time to maximum plasma concentration (median Tmax) was longer for manipulated ARYMO ER (2.1 hr) compared with crushed MS Contin® (0.9 hr)2
  • Exposure to morphine (mean AUC) was lower for manipulated ARYMO ER (159.3 h*ng/mL) compared with crushed MS Contin® (182.1 h*ng/mL)2

Cmax: Peak plasma concentration.

Tmax: Time required to reach Cmax.

AUC: Area under curve. Refers to the plasma drug concentration-time curve.

Attempting to cut, break, chew, crush, or dissolve ARYMO ER tablets may compromise some of the extended‑release properties, resulting in delivery of morphine that could lead to overdose and death.

DRUG LIKING

chart2_mobile.png

TAKE DRUG AGAIN

chart3_mobile.png

Although the results of the Oral Human Abuse Potential study demonstrated that the oral administration of manipulated ARYMO ER resulted in a statistically lower Mean Drug Liking score than the oral administration of crushed MS Contin®, there was no statistically significant reduction in the response to Take Drug Again. Therefore, it cannot be concluded that ARYMO ER has physical and chemical properties that are expected to reduce abuse via the oral route.2

Abuse of ARYMO ER by injection, as well as by oral and nasal routes, is still possible.

INTRANASAL ABUSE DATA

Data from the Intranasal HAP study are not included in the ARYMO ER label because FDA granted exclusivity to another ER morphine sulfate product for this labeling.