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      A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

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          To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide.


          This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility.


          Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again.


          Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.

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          Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing.

          Clinicians involved in the opioid pharmacotherapy of cancer-related pain should be acquainted with a variety of opioids and be skilled in the selection of doses when the type of opioid or route of administration needs changing. The optimal dose should avoid under-dosing or overdosing, both associated with negative outcomes for the patient. Although equianalgesic dose tables are generally used to determine the new doses in these circumstances, the evidence to support the ratios indicated in these tables largely refers to the context of single dose administration. The applicability of these ratios to the setting of chronic opioid administration has been questioned. A systematic search of published literature from 1966 to September 1999 was conducted to critically appraise the emerging evidence on equianalgesic dose ratios derived from studies of chronic opioid administration. There were six major findings: 1) there exists a general paucity of data related to long-term dosing and studies are heterogeneous in nature; 2) the ratios exhibit extremely wide ranges; 3) methadone is more potent than previously appreciated; 4) the ratios related to methadone are highly correlated with the dose of the previous opioid; 5) the ratio may change according to the direction the opioid switch; and 6) discrepancies exist with respect to both oxycodone and fentanyl. Overall, these findings have important clinical implications for clinicians and warrant consideration in the potential revision of current tables. The complexity of the clinical context in which many switches occur must be recognized and also appreciated in the design of future studies.
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            Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000.

            The treatment of pain has received increasing attention over the past decade promoted by national guidelines, the 'pain as the 5th vital sign' campaign and direct-to-consumer advertising. We examined national trends in office visits and analgesic treatment for musculoskeletal pain in the office setting, comparing data from 1980 and 2000. We analysed the National Ambulatory Medical Care Survey (NAMCS)--a nationally representative survey of visits to office-based physicians--using data from 1980-81 (n=89,000 visits) and 1999-2000 (n=45,000 visits). During this time, NSAID prescriptions increased for both acute (19 vs. 33%, RR=1.74; 95% CI, 1.52-1.95) and chronic (25 vs. 29%, RR=1.16; 95% CI, 0.97-1.35) musculoskeletal pain visits. In 2000, one-third of the NSAID prescriptions were for COX II agents. Opioids increased for acute pain (8 vs. 11%, RR=1.38; 95% CI, 0.92-1.83) and doubled for chronic pain (8 vs. 16%, RR=2.0; 95% CI, 1.52-2.48). The use of more potent opioids (hydrocodone, oxycodone, morphine) for chronic musculoskeletal pain increased from 2 to 9% of visits (RR=4.5; 95% CI, 2.18-6.87). This corresponds to 5.9 million visits where potent opioids were prescribed in 2000--an increase of 4.6 million visits from 1980 (assuming the total number of outpatient visits was constant at the 2000 level). In spite of the increased attention to pain treatment, there has not been an increase in office visits for musculoskeletal pain complaints. The threshold for prescribing NSAIDS and opioids, however, has dropped.
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              Opioid rotation: the science and the limitations of the equianalgesic dose table.

              Opioid rotation refers to a switch from one opioid to another in an effort to improve the response to analgesic therapy or reduce adverse effects. It is a common method to address the problem of poor opioid responsiveness despite optimal dose titration. Guidelines for opioid rotation are empirical and begin with the selection of a safe and reasonably effective starting dose for the new opioid, followed by dose adjustment to optimize the balance between analgesia and side effects. The selection of a starting dose must be based on an estimate of the relative potency between the existing opioid and the new one. Potency, which is defined as the dose required to produce a given effect, differs widely among opioids, and among individuals under varying conditions. To effectively rotate from one opioid to another, the new opioid must be started at a dose that will cause neither toxicity nor abstinence, and will be sufficiently efficacious in that pain is no worse than before the change. The estimate of relative potency used in calculating this starting dose has been codified on "equianalgesic dose tables," which historically have been based on the best science available and have been used with little modification for more than 40 years. These tables, and the clinical protocols used to apply them to opioid rotation, may need revision, however, as the science underlying relative potency evolves. Review of these issues informs the use of opioid rotation in the clinical setting and defines key areas for future research.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                08 July 2015
                : 8
                : 347-360
                [1 ]Pfizer Inc, Durham, NC, USA
                [2 ]Duke University Medical Center, Durham, NC, USA
                [3 ]Family Health Medical Services PLLC, Mayville, Buffalo, NY, USA
                [4 ]Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA
                [5 ]New York Spine & Wellness Center, Syracuse, NY, USA
                Author notes
                Correspondence: Beatrice Setnik, INC Research, Early Phase, 3201 Beechleaf Court, Suite 600, Raleigh, NC 27604, USA, Tel +1 919 227 5854, Fax +1 919 876 9360, Email beatrice.setnik@ 123456incresearch.com
                © 2015 Setnik et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Anesthesiology & Pain management

                equianalgesic, opioid conversion, safety, primary care, morphine, rotation


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