Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product

Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids) that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF). ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liabilit

Transdermal buprenorphine for moderate chronic noncancer pain syndromes

Introduction: Chronic noncancer pain has remained a challenging clinical problem. Opioid analgesics are effective, but they are known to be associated with opioid use disorder and potentially treatment-limiting side effects. Buprenorphine is a Schedule III synthetic opioid in the USA with a chemical structure similar to that of morphine but with a longer duration of action, greater potency, and other unique pharmacological attributes. Its role in treatment of chronic noncancer pain may be broader than currently thought. Areas covered: The pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile of transdermal buprenorphine in moderate chronic noncancer pain syndromes patients will be discussed. Expert commentary: Buprenorphine offers effective analgesia in the form of a Schedule III drug (rather than Schedule II such as oxycodone or morphine) and transdermal buprenorphine is a convenient, accepted, around-the-clock pain reliever. Its lower potential for abuse should make it a more desirable pain reliever but many payers do not reimburse buprenorphine, driving prescribers and their patients to generic versions of the riskier Schedule II oral opioids such as oxycodone and morphine

Management of moderate to severe chronic low back pain with buprenorphine buccal film using novel bioerodible mucoadhesive technology

Joseph V Pergolizzi Jr,1 Robert B Raffa,2,3 Charles Fleischer,1 Gianpietro Zampogna,1 Robert Taylor Jr1 1NEMA Research, Naples, FL, 2University of Arizona College of Pharmacy, Tucson, AZ, 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: With a global prevalence of ~9%–12%, low back pain (LBP) is a serious public health issue, associated with high costs for treatment and lost productivity. Chronic LBP (cLBP) involves central sensitization, a neuropathic pain component, and may induce maladaptive coping strategies and depression. Treating cLBP is challenging, and current treatment options are not fully satisfactory. A new BioErodible MucoAdhesive (BEMA®) delivery system for buprenorphine has been developed to treat cLBP. The buccal buprenorphine (BBUP) film developed for this product (Belbuca™) allows for rapid delivery and titration over a greater range of doses than was previously available with transdermal buprenorphine systems. In clinical studies, BBUP was shown to effectively reduce pain associated with cLBP at 12 weeks with good tolerability. The most frequently reported side effects with the use of BBUP were nausea, constipation, and vomiting. There was no significant effect on the QT interval vs placebo. Chronic pain patients using other opioids can be successfully rotated to BBUP without risk of withdrawal symptoms or inadequate analgesia. The role of BBUP in managing cLBP remains to be determined, but it appears to be a promising new product in the analgesic arsenal in general. Keywords: buccal, transmucosal, buprenorphine, chronic low back pain, BEMA, drug delivery Belbuc

Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

Joseph V Pergolizzi Jr,1 Robert B Raffa,2,3 Marco Pappagallo,4 Charles Fleischer,1 Joseph Pergolizzi III,1 Gianpietro Zampogna,5 Elizabeth Duval,1 Janan Hishmeh,1 Jo Ann LeQuang,1 Robert Taylor Jr1 1NEMA Research, Inc., Naples, FL, 2University of Arizona College of Pharmacy, University of Arizona, Tucson, AZ, 3Temple University School of Pharmacy, Temple University, Philadelphia, PA, 4Department of Medicine, Albert Einstein College of Medicine, New York, NY, 5Department of Medicine, St. Luke’s Hospital, Cleveland, OH, USA Abstract: Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone. Keywords: opioid-induced constipation, opioid bowel disorder, PAMORA, peripherally acting mu-opioid receptor antagonist, noncancer pain patients, opioid-associated side effect

Mitigating the risk of opioid abuse through a balanced undergraduate pain medicine curriculum

Patricia K Morley-Forster,1,2 Joseph V Pergolizzi,3–5 Robert Taylor Jr,5 Robert A Axford-Gatley,6 Edward M Sellers71Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, ON, Canada; 2Outpatient Pain Clinic, St Joseph’s Hospital, London, ON, Canada; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA; 5NEMA Research Inc, Naples, FL, USA; 6Clinical Content and Editorial Services, Complete Healthcare Communications, Inc, Chadds Ford, PA, USA; 7DL Global Partners Inc, Toronto, ON, CanadaAbstract: Chronic pain is highly prevalent in the United States and Canada, occurring in an estimated 30% of the adult population. Despite its high prevalence, US and Canadian medical schools provide very little training in pain management, including training in the safe and effective use of potent analgesics, most notably opioids. In 2005, the International Association for the Study of Pain published recommendations for a core undergraduate pain management curriculum, and several universities have implemented pilot programs based on this curriculum. However, when outcomes have been formally assessed, these initiatives have resulted in only modest improvements in physician knowledge about chronic pain and its treatment. This article discusses strategies to improve undergraduate pain management curricula and proposes areas in which those efforts can be augmented. Emphasis is placed on opioids, which have great potency as analgesics but also substantial risks in terms of adverse events and the risk of abuse and addiction. The authors conclude that the most important element of an undergraduate pain curriculum is clinical experience under mentors who are capable of reinforcing didactic learning by modeling best practices.Keywords: chronic pain, curricular content, medical education, opioids, pain education, pain knowledge, physician training, teachin