Arymo (morphine) / Assertio - LARVOL DELTA

Oxymorphone and Oxycodone Pharmacy Purchases in US Counties: Prelude to the Largest Rural Human Immunodeficiency Virus Outbreak in US History. (PubMed, Pharmacoepidemiol Drug Saf) - "Opana ER rapidly supplanted OxyContin in a vulnerable population that was at heightened risk for HIV who subsequently faced an immediate supply shock after its reformulation. Pharmacy transactions are critical for suspicious order monitoring and pharmacovigilance by US and international agencies especially during deleterious supply shocks in legal and illicit drug markets."

Journal • Human Immunodeficiency Virus • Infectious Disease

Differences in severity of poison centers exposures involving XTAMPZA ER versus other opioid analgesics. (PubMed, Pain Manag) - "Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodone and unspecified morphine. Results & No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators."

Journal • Pain

Sustained Risk Reduction of Severe Clinical Outcomes Following Misuse/Abuse of XTAMPZA ER as Compared to Other Prescription Opioids (PAINWeek 2023) - " Using NPDS data (01January2019 - 31December2022), frequency of misuse/abuse exposures and clinical outcomes were compared between XTAMPZA ER, other ER oxycodone (oral solid dosage forms of ER oxycodone excluding XTAMPZA ER), other ER opioids for analgesia (oral solid dosage forms of ER formulations of hydrocodone, oxymorphone, hydromorphone, morphine), and IR oxycodone (oral solid dosage forms)... This study suggests that XTAMPZA ER (an ADF ER oxycodone medication) may have a reduced risk of misuse/abuse than opioid medications compared in this study. Exposures to XTAMPZA ER reported to US poison centers were less likely to involve misuse/abuse than the opioid medications included in the other three study groups and no XTAMPZA ER exposure reported use by a nonoral route of administration, the routes associated with the highest risk for severe clinical outcomes. Life-threatening events and death were significantly less likely to occur with exposure to XTAMPZA ER than for..."

Clinical • Clinical data • Addiction (Opioid and Alcohol) • CNS Disorders • Pain

Differences in the severity of medical outcomes of exposures reported to poison centers involving XTAMPZA® ER and other opioid analgesics (PAINWeek 2023) - " There were 189 XTAMPZA ER exposures that were followed to a known outcome, of which, 19 (10.05%) were intentional (abuse/misuse/unknown) and 60 (31.75%) were suspected suicidal...All intentional exposures accounted for 2,815 (72.05%) cases reporting ADF extended-release (ER) opioids, 15,387 (77.78%) for not otherwise specified (NOS) oxycodone, 3,694 (61.45%) for immediate-release oxycodone, 3,569 (68.02%) for NOS morphine, and 1,190 (55.22%) for other ER opioids... XTAMPZA® ER was involved in fewer intentional abuse/misuse/unknown exposures and exposures overall reported to poison centers compared to other opioid analgesics. Across all exposure groups, XTAMPZA® ER resulted in less severe medical outcomes, which may be explained by lower numbers of intentional exposures and the effect of its ADF properties. No unintended routes for XTAMPZA® ER were reported."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry

Differences in the severity of medical outcomes of exposures reported to poison centers involving XTAMPZA® ER and other opioid analgesics (PAINWeek 2022) - "Data from cases involving 1) XTAMPZA ER, 2) immediate-release (IR) single-entity (SE) oxycodone 3) other ADF extended-release (ER) opioids, 4) non-ADF ER opioids 5) unspecified oxycodone, and 6) unspecified morphine were analyzed... We observed that a smaller percentage of XTAMPZA ER exposures reported to poison centers are categorized as either intentional misuse/abuse/unknown intentional or suspected suicidal compared to other opioids. Both the lower number of intentional exposures and lack of manipulation may explain the lower severity of medical outcomes for XTAMPZA ER across all exposures. Among intentional exposures involving XTAMPZA ER, no differences relative to other opioids were observed."

Addiction (Opioid and Alcohol) • CNS Disorders • Cognitive Disorders • Pain • Psychiatry

Abuse Deterrent in Use of Morphine Sulfate Extended Release (Arymo ER) in Patients with Prescribed Opioid Use for Post-operative or Cancer Treatments: A Systematic Review (ASHP 2021) - No abstract available

Clinical • Review • Oncology

Association of partial systemic exposure and abuse potential for opioid analgesics with abuse deterrence labeling claims supporting product-specific guidance. (PubMed, EClinicalMedicine) - "Extensive pharmacokinetic (PK) and subjective response data from 11 clinical abuse potential trials in recreational opioid users following oral and nasal administration of intact and manipulated oxycodone, hydrocodone and morphine products from the FDA internal database were utilized for the present analysis...Our findings support FDA's recommendation of comparative PK studies with early partial AUCs as a supportive PK metric for the assessment of abuse deterrent properties of generic opioid drug products in the general and product-specific guidance's of ADFs. The study was partially funded by Fiscal Year 2017 Critical Path of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration."

Journal • Pain

Abuse and misuse of XTAMPZA® ER relative to other opioid analgesics (PAINWeek 2021) - "ADF ER opioids included OxyContin®, Embeda®, Hysingla® ER, Arymo® ER, and MorphaBond™ ER... Abuse and misuse exposures involving XTAMPZA ER reported to poison centers and XTAMPZA ER abuse cases among individuals entering treatment for opioid use disorders are infrequent relative to comparators. No abuse or misuse of XTAMPZA ER via unintended routes of administration was reported in the Poison Center Program. The proportion of cases involving use via unintended routes of administration was lower for XTAMPZA ER than for comparator drug groups among individuals entering treatment for opioid use disorders."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Diversion and street price of XTAMPZA® ER relative to other prescription opioids (PAINWeek 2021) - "ADF ER opioids included OxyContin®, Embeda®, Hysingla® ER, Arymo® ER, and MorphaBond™ ER... Diversion of XTAMPZA ER was observed, though it comprised a smaller number of cases than would be expected based on prescription volume and drug potency. One appropriate comparator is IR oxycodone because it contains the same active ingredient in an easy to manipulate form. IR oxycodone had the highest number of cases."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry

Measuring Prescription Opioid Misuse and Its Consequences. (PubMed, Br J Clin Pharmacol) - "The rapid expansion of opioid prescribing was accompanied by increasing misuse and mortality. Interventions such as prescription drug monitoring programs (PDMP), increased law enforcement and abuse deterrent formulations have been followed by decreases in misuse of most opioid analgesics."

Journal • Pain • Substance Abuse

Postmarketing Analysis of Misuse, Abuse, and Diversion of Xtampza ER. (PubMed, Pain Med) - "Xtampza ER abuse, misuse, and diversion and tampering are low relative to other prescription opioid analgesics. Abuse and diversion did not increase over the study period."

Journal • P4 data • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Syringeability of morphine ARER, a novel, abuse-deterrent, extended-release morphine formulation. (PubMed, Am J Drug Alcohol Abuse) - "The difficulty to syringe morphine ARER when manipulated suggests that morphine ARER has abuse-deterrent properties that may deter intravenous abuse."

Journal

Reformulation of oxycodone 80 mg to prevent misuse: A cohort study assessing the impact of a supply-side intervention. (PubMed, Int J Drug Policy) - "Post-reformulation, more than half the cohort changed their filling patterns. Following reformulation, median MME dose decreased significantly among the cohort. We hypothesize that the dramatic decrease in MME dose prompted many to transition to heroin in order to avoid severe withdrawal."

Journal • Pain

A Randomized, Crossover Study on the Effect of Food on the Pharmacokinetic Characteristics of Morphine ARER (MorphaBond™ ER), an Abuse-Deterrent Formulation of Extended-Release Morphine. (PubMed, Adv Ther) - "Morphine ARER can be administered without regard to food. Plain language summary available for this article."

Clinical • Journal • PK/PD data • Pain

Pharmacodynamic Effects from a Category 3 Oral Human Abuse Potential Study of an Abuse-Deterrent, Extended-Release Morphine Product Candidate in Nondependent, Recreational Opioid Users (AAPMed 2017) - "Manipulated morphine-ADER-IMT may have lower abuse potential compared with crushed morphine ER when taken orally. The hardness of morphine-ADER-IMT makes manipulation and chewing difficult, presenting another significant barrier to misuse and abuse via the oral route."

Clinical • Addiction (Opioid and Alcohol) • Biosimilar • Pain

Egalet announces FDA advisory committee meeting will take place August 4, 2016 for lead abuse-deterrent candidate Arymo ER (morphine sulfate) extended-release tablets (Egalet Press Release) - "Egalet Corporation...announced today that a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee of the U.S. Food and Drug Administration (FDA) has been scheduled for August 4, 2016, to review the new drug application (NDA) for ARYMO™ ER...The FDA Prescription Drug User Fee Act (PDUFA) goal date for a decision is October 14, 2016."

Anticipated FDA event • PDUFA date • Demo Pain • Pain

Lipid microsphere bound oxycodone for pain management in patients receiving radiotherapy for head and neck cancer. (PubMed, Support Care Cancer) - "These results support the feasibility and safety of microsphere oxycodone for extended release analgesia among patients with HNC undergoing RT."

Clinical • Journal

Association Between Formulary Coverage and Use of Abuse-Deterrent Prescription Opioids, Risk for Abuse or Overdose, and Associated Healthcare Resource Utilization. (PubMed, Am Health Drug Benefits) - "An ADF opioid-including reformulated oxycodone hydrochloride (HCl) controlled-release (CR; reformulated OxyContin), morphine sulfate and naltrexone HCl extended-release (ER; Embeda), and hydrocodone bitartrate ER (Hysingla ER)-was considered covered if it was listed on the health plan's formulary...Broad formulary coverage of ADF opioids is associated with reduced rates of opioid abuse or overdose in real-world managed care populations. Health plan administrators and policymakers may consider improving the formulary coverage of ADF opioids as a strategy to ensure appropriate patient access to necessary pain medications while mitigating risk for opioid abuse or overdose."

HEOR • Journal

Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males - a double-blinded, randomized study. (PubMed, Br J Clin Pharmacol) - "Morphine : naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine: naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse."

Clinical • Journal

Modelling the potential impact of abuse-deterrent opioids on medical resource utilization. (PubMed, J Med Econ) - "Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events. Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids."

HEOR • Journal

Assessment of Tapentadol API Abuse Liability with the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System. (PubMed, J Pain) - "Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system...However, when adjusted for drug availability, event rates of abuse were lower than most CII opioids studied, but were not the lowest. Disentangling these two sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted."

Journal

Human abuse potential studies of abuse-deterrent opioids: lessons from oral and intranasal studies with morphine abuse-deterrent, extended-release, injection-molded tablets. (PubMed, Curr Med Res Opin) - "Results from HAP studies with morphine-ADER-IMT and other AD opioids, suggest that key study design features include the release profile (immediate-release vs extended-release) of the positive control, study drug doses, and the way the products are manipulated. These elements can directly impact the outcomes of the pharmacokinetic and pharmacodynamic (e.g., Maximum Drug Liking, Overall Drug Liking, and Take Drug Again) results. When evaluating HAP studies, it is important to understand study design features to assist in the interpretation of the results and understand the clinical relevance of the data to help guide clinical decision making about the use of AD opioids."

Journal

Relative Oral Bioavailability of an Abuse-Deterrent, Extended-Release Formulation of Morphine Versus Extended-Release Morphine: A 2-Period, Single-Dose, Randomized Crossover Study in Healthy Subjects. (PubMed, Clin Ther) - "These data show that, in these subjects, morphine ARER was bioequivalent to ER morphine, a treatment for pain with well-established efficacy and safety profiles."

Clinical • Journal

Relative Abuse of Crush-Resistant Prescription Opioid Tablets via Alternative Oral Modes of Administration. (PubMed, Pain Med) - "...CRTs (reformulated oxycodone extended-release [ER], reformulated oxymorphone ER, and tapentadol ER) were compared with non-CRT versions, morphine ER, and oxycodone immediate-release single entity...Results suggest the need for abuse-deterrent formulations designed to reduce abuse by oral administration with product manipulation, such as chewing. Advances in this area may reduce the overall abuse of prescription opioids and interrupt the progression from abuse by swallowing whole to oral administration involving product manipulation and other ROAs."

Journal

Mitigation of IV Abuse Through the Use of Abuse-Deterrent Opioid Formulations: An Overview of Current Technologies. (PubMed, Pain Pract) - "The available ADF opioids may decrease both the attractiveness and the feasibility of intravenous abuse. The adoption of ADF opioids represents one tactic for providing access to needed medication for patients with chronic pain, while potentially reducing the risk of opioid abuse, in a comprehensive effort to combat the opioid epidemic."

Journal • Review