Embeda (morphine & sequestered naltrexone) / Pfizer - LARVOL DELTA

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

Development and impact of prescription opioid abuse deterrent formulation technologies (Drug Alcohol Depend) - "Reviewed is the FDA recent approval of a product label describing the abuse deterrent characteristics of OxyContin® (physical barrier formulation), and the FDA determination that studies were insufficient for an Opana® (physical barrier) ADF label. Additional reviewed marketed OpAs with ADF technologies include: Suboxone® and Embeda® (opioid agonist/antagonist combinations), Oxecta® (aversion technology), and Nucynta® (physical barrier)....The outcomes of the recent ADF labeling applications for OxyContin® (Tier 3 approval) and Opana® (non-approval) suggest that the threshold for ADF labeling will be appropriately high."

Review • Pain

Pfizer reports fourth-quarter and full-year 2013 results; provides 2014 financial guidance (Businesswire) - Anticipated product availability for Embeda in Q2 2014; Anticipated submission of non clinical data to the FDA for tanezumab by the end of 2014.

Anticipated FDA event • Anticipated launch • Pain

Drug approval reports (FDA) - Embeda label revised on 16th Apr, 2014.

FDA event • Pain

Pfizer receives FDA approval for a prior approval supplement for Embeda (morphine sulfate and naltrexone hydrochloride) extended release capsules CII (Pfizer Press Release) - "Pfizer...announced today that the U.S. Food and Drug Administration (FDA) has approved a Prior Approval Supplement for EMBEDA®...Extended Release Capsules CII. The Prior Approval Supplement included an update to the EMBEDA manufacturing process that addressed the pre-specified stability requirement that led to the voluntary recall of EMBEDA from the market in March 2011.  Pfizer anticipates product availability in the second quarter of 2014."

Anticipated relaunch • FDA event • Pain

Pfizer: Annual Shareholders' Meeting (Pfizer) - Anticipated expiry of three formulation patents in US for pain in 2027

Anticipated patent expiry • Pain

Assessing the pharmacodynamic effects of oral and intranasal administration of crushed extended-release morphine/naltrexone capsules versus crushed controlled-release morphine tablets and placebo in nondependent recreational opioid users (AAPMed 2013) - Abstract #128; P1, N=33, N=80; NCT01595867; NCT01380093; Sponsor: Pfizer; “Irrespective of administration route, crushed MSN was associated with significantly lower mean peak effect (Emax) scores and effect over 2 h (AUE0-2) on subjective ratings of drug-liking and high compared with crushed MS (P<0.001), but ratings of drug-liking and high for crushed MSN and crushed MS were significantly greater relative to placebo (P<0.05).”

P1 data • Pain

Pfizer: Q1 2013 Results (Pfizer) - Anticipated regulatory submission of prior approval supplement for pain in 2013

Anticipated regulatory • Pain

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

Extended-release morphine sulfate and naltrexone hydrochloride (EMBEDA): naltrexone-associated withdrawal and abuse-related effects in patients with chronic pain and recreational opioid users. (PubMed, Curr Med Res Opin) - P1, P1/2, P3, P4; "When taken intact as directed, naltrexone in MSN does not precipitate withdrawal. However, when MSN is crushed, naltrexone mitigates, but does not eliminate, the euphorigenic effects of crushed morphine sulfate."

Clinical • Journal

Safety and Pharmacokinetic Study of EMBEDA in Children Ages 7-17 With Pain (clinicaltrials.gov) - P4; N=19; Terminated; Sponsor: Pfizer; N=140 ➔ 19; Completed ➔ Terminated; Pfizer released from post-marketing commitment and study terminated because too few patients in the age group; not because of efficacy or safety issues.

Clinical • Enrollment change • Trial termination

Safety and Pharmacokinetic Study of EMBEDA in Children Ages 7-17 With Pain (clinicaltrials.gov) - P4; N=140; Completed; Sponsor: Pfizer; Recruiting ➔ Completed

Trial completion

Real-world misuse, abuse, and dependence of abuse deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients. (PubMed, Postgrad Med) - "Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products."

Clinical • Journal • Medicaid • Real-World Evidence • Reimbursement