Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access.

The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion.

Efficacy and Safety of Naloxegol in Patients with Chronic Non-Cancer Pain Who Experience Opioid-Induced Constipation: A Pooled Analysis of Two Global, Randomized Controlled Studies.

Objective: This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment.

Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily.

Self-Healing: A Concept for Musculoskeletal Body Pain Management - Scientific Evidence and Mode of Action.

Traditionally, musculoskeletal pain management has focused on the use of conventional treatments to relieve pain. However, multi-modal integrative medicine including alternative/complementary treatments is becoming more widely used and integrated into treatment guidelines around the world. The uptake of this approach varies according to country, with generally a higher uptake in developed countries and in females aged more than 40 years.

Individual- and Community-Level Factors Associated With Detectable and Elevated Blood Lead Levels in US Children: Results From a National Clinical Laboratory.

Importance: No safe level of exposure to lead has been identified.

Objective: To evaluate individual- and community-level factors associated with detectable and elevated blood lead levels (BLLs) in children.

Design, Setting, And Participants: This cross-sectional, retrospective study analyzed deidentified results from blood lead tests performed at a large clinical laboratory from October 1, 2018, to February 29, 2020.

Open-Label Adhesion Performance Studies of a New Lidocaine Topical System 1.8% versus Lidocaine Patches 5% and Lidocaine Medicated Plaster 5% in Healthy Subjects.

Purpose: The primary objective was to evaluate adhesion performance of the lidocaine topical system 1.8% for 12 hours in healthy human subjects in three studies: as a single product (Study 1) and versus other lidocaine topical products (lidocaine patch 5% and lidocaine medicated plaster 5% [Study 2] and generic lidocaine patch 5% [Study 3]). Safety of the lidocaine topical system 1.

Characteristics of Analgesic Patch Formulations.

Topical and transdermal formulations are a common means of pharmaceutical drug delivery. If a drug is able to penetrate transcutaneously, the skin is an ideal site for the delivery of medications for both local (topical) and systemic (transdermal) effects. The administration of analgesics through the skin poses several potential advantages to those administered orally including compliance, the ability to deliver a drug to a peripheral target site and more stable and sustained plasma levels.

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks.

Improvement of Pain and Function After Use of a Topical Pain Relieving Patch: Results of the RELIEF Study.

Purpose: Pain is the most common reason for patients to consult primary care providers. Identification of effective treatments with minimal adverse events is critical to safer opioid-sparing and multi-modal approaches to pain treatment. Topical analgesic patches target medication to peripheral sites of pain while potentially avoiding adverse effects associated with systemic medications.

A Randomized, Open-Label, Bioequivalence Study of Lidocaine Topical System 1.8% and Lidocaine Patch 5% in Healthy Subjects.

Purpose: This study was designed to characterize drug delivery with lidocaine topical system 1.8% vs lidocaine patch 5% through 2 PK studies.

Patients And Methods: Two Phase 1, single-center, open-label, randomized PK studies were performed in healthy adults.

Reducing Opioid Prescriptions by Identifying Responders on Topical Analgesic Treatment Using an Individualized Medicine and Predictive Analytics Approach.

Purpose: Chronic pain is a life changing condition, and non-opioid treatments have been lately introduced to overcome the addictive nature of opioid therapies and their side effects. In the present study, we explore the potential of machine learning methods to discriminate chronic pain patients into ones who will benefit from such a treatment and ones who will not, aiming to personalize their treatment.

Patients And Methods: In the current study, data from the OPERA study were used, with 631 chronic pain patients answering the Brief Pain Inventory (BPI) validated questionnaire along with supplemental questions before and after a follow-up period.

Are Opioids Needed to Treat Chronic Low Back Pain? A Review of Treatment Options and Analgesics in Development.

The continued prevalence of chronic low back pain (CLBP) is a testament to our lack of understanding of the potential causes, leading to significant treatment challenges. CLBP is the leading cause of years lived with disability and the fifth leading cause of disability-adjusted life-years. No single non-pharmacologic, pharmacologic, or interventional therapy has proven effective as treatment for the majority of patients with CLBP.

Safe Opioid Storage and Disposal: A Survey of Patient Beliefs and Practices.

Objective: To evaluate knowledge, practices, and beliefs of US patients receiving prescription opioids regarding opioid storage, disposal, and diversion.

Design: Internet-based, cross-sectional survey conducted between September and October 2018. Fisher's exact tests and Kendall's Tau-c were used to assess associations with storage and disposal outcomes.

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza ER (oxycodone DETERx formulation): A review of published studies.

Opioids can be an effective treatment option for appropriate patients with chronic pain for whom nonpharmacological or nonopioid treatment does not provide adequate pain relief. However, extended-release (ER) opioid formulations, because of their high drug content, are attractive options for nonmedical use and abuse. Xtampza ER (oxycodone DETERx) capsules, an ER abuse-deterrent formulation (ADF), contain microspheres that combine oxycodone with inactive ingredients to increase the difficulty of tampering with the ER mechanism.

Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions.

Opioid analgesics remain a treatment option for refractory acute and chronic pain, despite their potential risk for abuse and adverse events (AEs). Opioids are associated with several common AEs, but the most bothersome is opioid-induced constipation (OIC). OIC is often overlooked but has the potential to affect patient quality of life, increase associated symptom burden, and impede long-term opioid compliance.

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

Objective: To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.

Design: Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).

Setting: Conducted in the United States at multiple sites.

A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain.

Buprenorphine is a Schedule III opioid analgesic with unique pharmacodynamic and pharmacokinetic properties that may be preferable to those of Schedule II full μ-opioid receptor agonists. The structure of buprenorphine allows for multimechanistic interactions with opioid receptors μ, δ, κ, and opioid receptor-like 1. Buprenorphine is considered a partial agonist with very high binding affinity for the μ-opioid receptor, an antagonist with high binding affinity for the δ- and κ-opioid receptors, and an agonist with low binding affinity for the opioid receptor-like 1 receptor.

Understanding Buprenorphine for Use in Chronic Pain: Expert Opinion.

Objective: An expert panel convened to reach a consensus on common misconceptions surrounding buprenorphine, a Schedule III partial µ-opioid receptor agonist indicated for chronic pain. The panel also provided clinical recommendations on the appropriate use of buprenorphine and conversion strategies for switching to buprenorphine from a full µ-opioid receptor agonist for chronic pain management.

Methods: The consensus panel met on March 25, 2019, to discuss relevant literature and provide recommendations on interpreting buprenorphine as a partial µ-opioid receptor agonist, prescribing buprenorphine before some Schedule II, III, or IV options, perioperative/trauma management of patients taking buprenorphine, and converting patients from a full µ-opioid receptor agonist to buprenorphine.

The prescription opioid conundrum: 21st century solutions to a millennia-long problem.

Health-care professionals are faced with a daunting task: balancing appropriate care for chronic pain with their responsibility to keep patients and others safe from treatment-related harm. Whereas opioids have historically been considered an effective tool in the analgesic armamentarium, the rise of opioid abuse has caused the pendulum to swing away from prescribing opioids to an emphasis on safety. This paradigm shift risks neglecting the very real consequences of untreated/undertreated pain.

Treatment Patterns and Medication Use in Patients with Postherpetic Neuralgia.

Background: Postherpetic neuralgia (PHN) is a chronic, painful condition characterized by persistent pain following resolution of a herpes zoster (HZ) infection. Epidemiologic data demonstrate that the risks for HZ infections and the development of PHN increase with age.

Objective: To characterize prescribing patterns, health care utilization, and treatment costs for adults with PHN based on real-world data.

Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS).

Objective: To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).

Design: Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).

Setting: Multicenter, long-term clinical research study.

Assessment of potentially abuse-related events in two phase 3 studies of NKTR-181, a novel opioid analgesic, using the MADDERS® system (Misuse, Abuse, and Diversion Drug Event Reporting System).

To prospectively evaluate the abuse potential of NKTR-181, a novel opioid analgesic, in two phase 3 clinical trials using a newly developed reporting system: the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS®). SUMMIT-07 was an enriched enrollment randomized withdrawal study that examined the safety and efficacy of NKTR-181 across 12 weeks in opioid-naïve subjects with chronic low back pain. SUMMIT-LTS was a 52 week open-label study in opioid-naïve and experienced subjects with chronic low back pain or noncancer pain rolled over from SUMMIT-07 or enrolled .

SUMMIT-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain.

NKTR-181, a new molecular entity, mu-opioid receptor agonist with an inherently slow rate of central nervous system (CNS) entry, was designed to provide analgesia while reducing abuse potential. This phase 3, enriched-enrollment, randomized-withdrawal trial evaluated the analgesic efficacy, safety, and tolerability of NKTR-181 in patients with chronic low-back pain (CLBP). Adults with moderate-to-severe CLBP refractory to nonopioid analgesics achieving an analgesic NKTR-181 dosage (100-400 mg twice daily) during the open-label titration period were randomized to continued NKTR-181 treatment, double-blind, or switched to placebo.