Extended-release Opioids Research Articles

Federal Agencies Call for Opioid Training

Federal Agencies Call for Opioid Training

Physicians Key to Strategy for Reducing Opioid Abuse

Under a new White House plan to curtail prescription drug abuse, physicians would receive training in the prescribing of long-acting and extended-release opioids. APA has voiced its support for the plan.

A pilot study comparing pain intensity before and after conversion from patient controlled analgesia (PCA) to oral or transdermal extended-release opioids

The primary objective of this study was to compare patients' self-reported pain intensity, level of satisfaction with their pain control, and side effects (drowsiness, pruritis, urinary retention, nausea and vomiting) before and after conversion from IV PCA to oral or transdermal extended-release opioids using a novel approach of initiating the oral or transdermal opioid prior to discontinuation of the PCA. Additionally, we collected the number of supplemental analgesic rescue doses required and opioid dose before and after conversion, as secondary endpoints.

Anesthesia Literature Review

Anesthesia Literature Review

Development of Tamper Deterrent Formulations: State of the Pharmaceutical Industry

Prescription drug abuse is a significant and growing health and socio-economical problem in the US and the world. According to the 2008 UN World Drug Report, the number of people who have consumed an illicit drug at least once in 2006/2007 reached 240 million, roughly 6% of the world population aged 15 to 64. In the last few years, pharmaceutical manufacturers started developing new formulations specifically designed to provide tamper deterrent features. The initial focus of these development activities was extended release opioids, owing to their dominant share of reported prescription drug abuse. Tamper deterrent formulations (TDF) for other drugs of abuse, including stimulants and sedatives are also in various stages of development. Three major challenges face the development of TDF: the increased sophistication of the tampering methods used by abusers, the ambiguity of the regulatory requirements for labeling and marketing and the exaggerated expectations of what these formulations can deliver. This review details the approaches used by pharmaceutical manufacturers to impart tamper deterrent features into their formulations; the in vitro and in vivo tests that have been proposed or used to assess the performance of TDF; and the current regulatory landscape.

Chronic pain management issues in the primary care setting and the utility of long-acting opioids

Importance of the field: Chronic/persistent pain – a highly prevalent condition that places a substantial burden on patients in terms of personal suffering, reduced productivity and health care costs – remains inadequately treated in many patients. The purpose of this review is to provide an overview and evaluate the burden and undertreatment of chronic/persistent pain, considerations for choosing an analgesic and the utility of long-acting opioids.Areas covered in this review: A PubMed search was conducted to identify randomized, placebo-controlled trials evaluating the efficacy and safety of long-acting opioids in chronic pain conditions. The following search terms were used: long-acting opioids, extended-release opioids, controlled-release opioids, sustained-release opioids, and transdermal opioids. The search was limited to randomized, controlled trials published within the last 10 years (1998 – 2008). Studies meeting the following criteria were excluded from review: those focused on a neuropathic pain condition or specific patient subpopulations (e.g., opioid-experienced patients); those conducted outside the USA; and those evaluating a long-acting opioid that is not on the US market at present.What the reader will gain: The reader will first develop a better understanding of the individual and societal ramifications of undertreated chronic pain. Then, a critical review of safety and efficacy data from well-controlled randomized studies will help readers understand the choices and variables that should be considered when selecting appropriate treatments for patients with chronic pain.Take home message: Successful management of chronic/persistent pain should be individually tailored to each patient, taking into account his or her pain intensity and duration, disease state, tolerance of adverse events and risk of medication abuse or diversion. The literature supports the efficacy and safety of a number of long-acting opioids for the treatment of moderate to severe chronic pain, demonstrating sustained improvements in pain intensity and pain-related sleep disturbances with these agents.

User acceptance and performance assessment of an opioid REMS system: a pilot study

FDA is considering a class-wide REMS for extended-release (ER) opioids and methadone, but given that this would become the largest REMS (>20 million Rx's/year), successful implementation requires a new model that minimizes undue burden on healthcare providers, ensures appropriate access to patients, and documents relevant measures. Current enrollment verification systems that employ website lookup or interactive voice response (IVR) are viewed as cumbersome and not scalable. New systems must accommodate large volumes of prescriptions quickly and accurately and be integrated into the pharmacist's workflow to ensure compliance. The objective of this study was to evaluate user acceptance and system performance of a REMS system comprising prescriber and patient education, stakeholder enrollment, and point-of-dispensing verification of safe-use conditions in patients receiving opioids. Four prescribers completed baseline assessments of risk knowledge, self-efficacy in managing opioid risks, and adherence to safe use guidelines. They also completed a 30-minute educational program on safe opioid prescribing and attested, using an online enrollment form, to following safe use guidelines. Patients completed similar baseline assessments (knowledge, self-efficacy, adherence) prior to their office visits and received education on general and product-specific safe use guidelines. Basic patient demographic information was entered into the REMS database. Eight patients and two prescribers were manually “de-enrolled” to test the ability of the system to discriminate “valid” (enrolled) from “invalid” (unenrolled) stakeholders. Prescriptions were filled at 1 of 2 study pharmacies, and as a part of the normal electronic adjudication process, the pharmacy claim was routed to the REMS database to verify enrollment. Prescribers and patients completed post-interventional surveys on risk knowledge, self-efficacy, and adherence to safe use guidelines, and all study participants, including pharmacists, completed a system usability survey. Enrollment is ongoing (target n = 16). Survey and performance data will be presented, and policy/public health implications will be discussed.

Panel Backs Extended-Release Opioid's Risk Plan

Panel Backs Extended-Release Opioid's Risk Plan

Opioid Prescribing Practices in Chronic Pain Management: Guidelines Do Not Sufficiently Influence Clinical Practice

To examine the use of extended-release (ER) opioids relative to immediate-release (IR) opioids in chronic opioid prescription episodes, pharmacy claim data from a national health plan database were analyzed. Enrollees having at least 1 pharmacy claim for an opioid formulation between June 2003 and May 2006, and at least 1 year of continuous enrollment after their first observed pharmacy claim were included. Opioid prescription episodes were created by combining contiguous days of therapy, allowing for a maximum of 7 days between refills (>or=8 d = new episode). Outcomes are reported in the form of probabilities and odds ratios (ORs). A total of 3,993,011 opioid prescription episodes were derived from 1,967,898 enrollees. Overall, prescription episodes involving IR preparations (97.7%) were more prevalent than episodes using ER preparations (2.3%). The odds of an ER preparation being prescribed chronically (>or=60 d) were approximately 11 times that of an IR preparation (OR = 10.7); however, the majority of chronic prescription episodes used IR formulations (84.8%). When stratified by prescriber type (specialist vs nonspecialists), the probability of a specialist prescribing ER opioids in these chronic prescription episodes was 19.1% versus 13.7% for nonspecialists. Specialists were about 50% more likely to prescribe ER opioids relative to nonspecialists (OR = 1.49). This analysis suggests that the availability of pain-treatment guidelines, recommendations, and education alone may not be enough to influence opioid-prescribing practices in the treatment of chronic pain.

Benefits of Extended‐Release Opioid Analgesic Formulations in the Treatment of Chronic Pain

Chronic noncancer pain represents a major health problem that affects many patients, resulting in suffering, reduced productivity, and substantial health care costs. The patient with chronic noncancer pain is burdened by decreased quality of life, decreased sleep, interference with social relationships, diminished cognitive functions, interference with activities of daily living, decreased productivity, and increased anxiety and depression. A survey examining the burden of pain on health and productivity found decreases of 45% in physical health and 23% in mental health at a cost of $61.2 billion per year in productive work time. An American Pain Society survey of 800 patients with moderate to severe chronic pain reported that 47% felt their pain was not under control. The goal of pharmacological therapy for chronic noncancer pain is to provide sustained analgesia. Chronic pain management guidelines recommend the use of long-acting, extended-release (ER) analgesics because they provide prolonged, more consistent plasma concentrations of drug compared with short-acting agents, thus minimizing fluctuations that could contribute to end-of-dose breakthrough pain. ER analgesics offer more consistent and improved nighttime pain control, less need to awaken at night to take another dose of pain medication, and less clock-watching by patients in chronic noncancer pain. Among the available ER opioids, tramadol ER possesses a unique mechanism of action, making it a viable opioid of first choice for patients suffering from a variety of chronic noncancer pain conditions, such as osteoarthritis, low back pain, and neuropathic pain.

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

Extended-release opioids for the management of chronic non-malignant pain

Recent clinical trials have documented the use of extended-release (ER) opioids in the management of chronic non-malignant pain. This manuscript reviews the clinical pharmacology of investigational and current marketed ER opioids. Recent randomised clinical trials of ER opioids that document the efficacy and safety of opioid therapy for chronic pain are reviewed. Finally, the abuse liability of ER opioids is discussed. Current technologies aimed at defeating the abuse of ER opioids will also be presented.

Comparative Tolerability of the Newer Agents Used for the Treatment of Neuropathic Pain

AbstractAn increasing number of drugs are now available for the treatment of neuropathic pain. The evidence base that surrounds the use of the newer agents is, as yet, not as solid as those agents which have been available for some time. It does, however, appear that the majority of these newer agents, or new formulations of older agents, are at least as effective as those previously available, but with distinct advantages in terms of incidence and severity of side effects and hence have an increased chance of being tolerated by the patient. Insufficient evidence allows definitive statements regarding the comparative tolerability of the recently introduced agents. It appears that, in general, antiepileptic drugs are better tolerated than the antidepressants and that extended release opioids are better tolerated than those which are immediate release. As no one drug will relieve neuropathic pain in all suffers, the availability of a number of agents with enhanced tolerability when compared to older agents ...

The metamorphosis of hydromorphone

Hydromorphone, one of the oldest and most potent of opioids, is an effective alternative to morphine. With a variety of routes of administration, it has an efficacy similar to that of morphine. The FDA has recently approved the first commercially available extended-release formulation, a once-daily hydromorphone for the management of moderate to severe pain in opioid tolerant individuals with an anticipated extended period of use. The formulation exhibits less peak-to-trough fluctuation in plasma concentration, while providing analgesia statistically indistinguishable from its immediate-release counterpart. The manufacturer and the FDA have articulated a plan to minimize unskillful prescribing and abuse/diversion through education, supply-chain integrity, and surveillance. It is anticipated that Palladone will be a valuable addition to the limited armamentarium of extended-release opioids.

Comparative Tolerability of the Newer Agents Used for the Treatment of Neuropathic Pain

An increasing number of drugs are now available for the treatment of neuropathic pain. The evidence base that surrounds the use of the newer agents is, as yet, not as solid as those agents which have been available for some time. It does, however, appear that the majority of these newer agents, or new formulations of older agents, are at least as effective as those previously available, but with distinct advantages in terms of incidence and severity of side effects and hence have an increased chance of being tolerated by the patient. Insufficient evidence allows definitive statements regarding the comparative tolerability of the recently introduced agents. It appears that, in general, antiepileptic drugs are better tolerated than the antidepressants and that extended release opioids are better tolerated than those which are immediate release. As no one drug will relieve neuropathic pain in all suffers, the availability of a number of agents with enhanced tolerability when compared to older agents at least gives hope that further therapeutic options can be tried in the sufferer of neuropathic pain in whom the first intervention is unsuccessful.