Immediate-release Morphine Research Articles

Current Status of Cognition and Clinical Practice of Refractory Cancer Pain in Shanghai: A Questionnaire Survey.

This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai. From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China. A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training. Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.

Knowledge and practice of the management of breakthrough cancer pain among general practitioners providing palliative care in Shanghai, China: a cross-sectional survey

ObjectiveThis study examined knowledge and practice of breakthrough cancer pain (BTcP) management among general practitioners (GPs) providing palliative care in Shanghai.DesignCross-sectional study using a self-administered questionnaire.Setting and participantsA total of...

Efficacy and tolerability of oral morphine versus oxycodone/acetaminophen for analgesia in the emergency department.

Oxycodone/acetaminophen is one of the most commonly prescribed medications for pain management in the emergency department (ED) despite its high abuse liability. Our objective was to determine whether oral immediate-release morphine is as effective and well tolerated as oral oxycodone/acetaminophen for pain relief in stable ED patients. This is a prospective comparative study in which stable adult patients with acute painful conditions who had either oral morphine (15 or 30 mg) or oxycodone/acetaminophen (5/325 mg or 10/650 mg) ordered for them at the discretion of a triage physician were recruited. This study took place in an urban, academic ED from 2016 to 2019. Seventy-three percent of the subjects were between the ages of 18 and 59, 57 percent were female, and 85 percent were African American. Most presented with abdominal, extremity, or back pain. Patient characteristics were similar between treatment groups. Of the 364 enrolled patients, 182 were given oral morphine and 182 were given oxycodone/acetaminophen at the discretion of the triage provider. They were asked to rate their pain score prior to receiving analgesia and at 60 and 90 minutes after administration. We examined pain scores, adverse effects, overall satisfaction, willingness to accept the same treatment again, and the need for additional analgesia. There was no difference in satisfaction reported by patients who received morphine versus oxycodone/acetaminophen: 15.9 percent vs 16.5 percent were very satisfied, 31.9 percent vs 26.4 percent were somewhat satisfied, and 23.6 percent vs 22.5 percent were not satisfied, p = 0.56. Secondary outcomes also showed no significant difference: net change in pain score -2 vs -2 at 60 and 90 minutes, p = 0.91 and p = 0.72, respectively; adverse effects 20.9 percent vs 19.2 percent, p = 0.69; need for further analgesia 9.3 percent vs 7.1 percent, p = 0.44; willingness to accept analgesic again 73.1 percent vs 78.6 percent, p = 0.22. Oral morphine is a feasible alternative to oxycodone/acetaminophen for analgesia in the ED.

How does controlled-release (CR) oxycodone compare with immediate-release oxycodone or CR morphine for people with cancer-related pain?

How does controlled-release (CR) oxycodone compare with immediate-release oxycodone or CR morphine for people with cancer-related pain?

Study on dosage range evaluation opioid analgesic for breakthrough pain in cancer patients: a retrospective study.

Breakthrough pain is an exacerbation of pain occurring in patients with chronic pain who receive opioid therapy every day. Breakthrough pain has not been routinely recognized, evaluated and treated. This study aimed to analyze the utilization of opiates analgesics, including dose regimentation, frequency of use, and the actual adverse effects in cancer patients with breakthrough pain. Data were collected by the retrospective method in the period from January to December 2017. Patients involved received opioids around the clock for treating background pain and rescue medication for treating breakthrough pain. The percentage of the rescue medication dose was calculated based on the total daily opioid dose to treat background pain. Descriptive analysis was used. From 335 visits, there were 334 of patient visit where the patient received immediate-release morphine as a rescue medication with a dose percentage between 6.67-60%, and 1 visit where the patient received codeine with a dose percentage of 16.67%. Of 335 visits, 233 patient visits received the right proportion of opioid rescue medication doses, while 102 patient visits received a greater dose proportion than the recommended dose of 5-20%. Immediate-release morphine is the most commonly prescribed analgesic to treat breakthrough pain and used at 6.67-60% of daily dose with the frequency of use between 2 to 6 times a day. There were 189 (56.42%) patient visits when the patient experienced the adverse effects of the opioid. The identified actual adverse effects are constipation, nausea, and vomiting.

Efficacy and Safety of Tapentadol Immediate Release for Acute Pain: A Systematic Review and Meta-Analysis.

Tapentadol (TAP) immediate release (IR) is a newer opioid option for acute pain. The aim of this systematic review was to examine the efficacy and safety of TAP IR compared with other opioids for acute pain. A systematic literature search as conducted using the Cochrane Library, Embase, International Pharmaceutical Abstracts, MEDLINE, PubMed, and Web of Science. The search included all randomized controlled trials and observational studies examining TAP IR versus other orally administered IR opioids for acute pain. The protocol for this study was registered on PROSPERO (CRD42018110267). Thirteen studies and 1 abstract were included in the systematic review (n=12,814 patients). Of these, 5 studies and 1 abstract were included in the qualitative review (n=9108 patients). Eight randomized controlled trials (n=3706 patients) comparing 50 to 100 mg TAP IR versus 5 to 15 mg oxycodone IR were included in the meta-analysis. The lowest dose of TAP IR (ie, 50 mg) was associated with less pain control compared with oxycodone IR (standardized mean difference=0.25, 95% confidence interval: 0.06-0.44, P<0.01). However, there were no significant differences at higher doses (ie, 75, 100 mg, or when a titration strategy was used). In the qualitative analysis, pain control with TAP IR was also similar to morphine IR and tramadol IR. TAP IR was less likely to have gastrointestinal adverse effects such as nausea and constipation compared with other opioids. TAP IR is as effective as other opioids at higher doses for acute pain and is associated with fewer gastrointestinal adverse effects. On the basis of these findings, TAP IR can be considered as a first-line opioid for acute pain.

Indian Society for Study of Pain, Cancer Pain Special Interest Group Guidelines on Pharmacological Management of Cancer Pain (Part II).

The Indian Society for Study of Pain (ISSP), Cancer Pain Special Interest Group (SIG) guidelines on pharmacological management of cancer pain in adults provide a structured, stepwise approach, which will help to improve the management of cancer pain and to provide the patients with a minimally acceptable quality of life. The guidelines have been developed based on the available literature and evidence, to suit the needs, patient population, and situations in India. A questionnaire, based on the key elements of each sub draft addressing certain inconclusive areas where evidence was lacking, was made available on the ISSP website and circulated by e-mail to all the ISSP and Indian Association of Palliative Care members. We recommend that analgesics for cancer pain management should follow the World Health Organization 3-step analgesic ladder appropriate for the severity of pain. The use of paracetamol and nonsteroidal anti-inflammatory drugs alone or in combination with opioids for mild-to-moderate pain should be used. For mild-to-moderate pain, weak opioids such as tramadol, tapentadol, and codeine can be given in combination with nonopioid analgesics. We recommend morphine as the opioid of the first choice for moderate-to-severe cancer pain. Sustained-release formulations can be started 12 hourly, once the effective 24 h dose with immediate-release morphine is established. Opioid switch or rotation should be considered if there is inadequate analgesia or intolerable side effects. For opioid-induced respiratory depression, μ receptor antagonists (e.g. naloxone) must be used promptly. Antidepressants and/or anticonvulsants should be used to treat neuropathic cancer pain, and the dose should be titrated according to the clinical response and side effects. External beam radiotherapy should be offered to all patients with painful metastatic bone pain. There is evidence on use of ketamine in cancer neuropathic pain, but with no beneficial effect, thus, it is not recommended.

Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial

IntroductionMorphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and...

Controlled-Release Oxycodone vs. Placebo in the Treatment of Chronic Breathlessness—A Multisite Randomized Placebo Controlled Trial

ContextChronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated. ObjectivesDoes oxycodone reduce chronic breathlessness compared with placebo? MethodsA multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0–100 mm visual analogue scale) comparing arms Days 5–7. Secondary end points were average and worst breathlessness, quality of life, function, and harms. ResultsOf 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001). ConclusionThere was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness.

Real-life management of patients with breakthrough cancer pain caused by bone metastases in Spain.

Purpose: We aimed to explore the characteristics, and real-life therapeutic management of patients with breakthrough cancer pain (BTcP) caused by bone metastases in Spain, and to evaluate physicians’ opinion of and satisfaction with prescribed BTcP therapy.Participants and methods: For the purposes of this study, an ad-hoc questionnaire was developed consisting of two domains: a) organizational aspects and care standards; b) clinical and treatment variables of bone metastatic BTcP patients. In addition, physicians’ satisfaction with their prescribed BTcP therapy was assessed. Specialists collected data from up to five patients receiving treatment for BTcP caused by bone metastasis, all patients gave their consent to participate prior to inclusion.Results: A total of 103 cancer pain specialists (radiation oncologists [38.8%], pain specialists [33.0%], and palliative care (PC) specialists [21.4%]) were polled, and data on 386 BTcP patients with bone metastatic disease were collected. Only 33% of the specialists had implemented specific protocols for BTcP management, and 19.4% had established referral protocols for this group of patients. Half of all participants (50.5%) address quality of life and quality of care in their patients; however, only 27.0% did so from the patient’s perspective, as they should do. Most patients had multiple metastases and were prescribed rapid-onset fentanyl preparations (71.2%), followed by immediate-release morphine (9.3%) for the treatment of BTcP. Rapid-onset fentanyl was prescribed more often in PC units (79.0%) than in pain units (75.9%) and radiation oncology units (61.1%) (p<0.01). Furthermore, most physicians (71.8%) were satisfied with the BTcP therapy prescribed.Conclusions: Our results demonstrate the need for routine assessment of quality of life in patients with bone BTcP. These findings also underscore the necessity for a multidisciplinary therapeutic strategy for breakthrough pain in clinical practice in Spain.

The Current Practice of Opioid for Cancer Dyspnea: The Result From the Nationwide Survey of Japanese Palliative Care Physicians

ContextMorphine is recommended as the first-line pharmacological therapy for cancer dyspnea. However, the detailed practice of morphine has not been evaluated and consensus about other opioids for cancer dyspnea has not been established. ObjectivesTo explore the physician-reported practice of opioid for cancer dyspnea. MethodsA nationwide mail-questionnaire survey was conducted among 536 Japanese certified palliative care physicians. We randomly selected 268 and asked the following: 1) how the physicians themselves initiate and use morphine for cancer dyspnea, 2) opioid choice for dyspnea in patients who have already used opioid other than morphine regularly, and 3) opioid choice for dyspnea in patients with various degrees of renal impairment in their daily practice. ResultsOverall, 192 physicians responded (response rate, 71.6%). The major (58.3%) practice of initiating morphine was “immediate-release morphine as needed” in opioid-naïve patients, and the mean % increase when they titrate morphine for cancer dyspnea was 29.4 ± 11.3% of the baseline dose. Although “titrate baseline oxycodone” was the most frequent (42.3%) for low-to-moderate–dose regular oxycodone cases, “stepwise switch to morphine” (30.0%) and “add morphine on baseline oxycodone” (27.1%) were the more frequent practices for high-dose regular oxycodone. Regardless of the baseline dose, “add morphine on baseline fentanyl” was the most frequent practice for regular transdermal fentanyl cases. Oxycodone was the most frequent choice in renal insufficiency cases, regardless of its degree. ConclusionsAmong Japanese palliative care physicians, using oxycodone for cancer dyspnea was relatively popular practice, whereas fentanyl was not. Oxycodone was the most preferred opioid for cancer dyspnea in the setting of renal insufficiency among Japanese palliative care physicians. We should conduct studies to confirm the safety and effectiveness of these opioid practices for cancer dyspnea.

Tapentadol immediate release for moderate to severe acute post-surgery pain.

To investigate efficacy and tolerability of tapentadol immediate release (IR) in the treatment of moderate to severe acute pain in three surgical pain models. Three randomized, double-blind, placebo- and active-controlled, multicenter, phase 3 trials were performed in total hip replacement surgery, abdominal hysterectomy, and bunionectomy with trial medications administered every 4-6 hours as needed for up to 72 hours. Tapentadol IR was included in all trials, oxycodone IR in the total hip replacement trial, and morphine IR in the abdominal hysterectomy and bunionectomy trials; active controls ensured assay sensitivity. The primary efficacy endpoint was the sum of pain intensity differences over the first 24 hours of treatment (SPID24) in the abdominal hysterectomy trial and SPID48 in the other two trials. Tolerability was assessed by adverse events reporting. A total of 330, 832, and 285 patients with total hip replacement, abdominal hysterectomy, and bunionectomy, respectively, were assessed for efficacy. All three trials demonstrated statistically significant improvements of tapentadol IR on the primary endpoint versus placebo and similar improvements compared to morphine IR or oxycodone IR. These findings were consistent with results of total pain relief assessments and patients' global impressions of change in their overall health status after 72 hours (abdominal hysterectomy, bunionectomy). The tolerability profile of tapentadol IR was as expected for a centrally acting analgesic in the post-surgery setting. Tapentadol IR has strong analgesic efficacy and is well tolerated in multiple post-surgery conditions of moderate to severe pain.

The Indian Society for Study of Pain, Cancer Pain Special Interest Group guidelines on pharmacological management of cancer pain (Part II)

The Indian Society for Study of Pain (ISSP), Cancer Pain Special Interest Group (SIG) guidelines on pharmacological management of cancer pain in adults provide a structured, stepwise approach, which will help to improve the management of cancer pain and to provide the patients with a minimally acceptable quality of life. The guidelines have been developed based on the available literature and evidence, to suit the needs, patient population, and situations in India. A questionnaire, based on the key elements of each subdraft addressing certain inconclusive areas where evidence was lacking, was made available on the ISSP website and circulated by e-mail to all the ISSP and Indian Association of Palliative Care members. We recommend that analgesics for cancer pain management should follow the World Health Organization 3-step analgesic ladder appropriate for the severity of pain. The use of paracetamol and nonsteroidal anti-inflammatory drugs alone or in combination with opioids for mild-to-moderate pain should be used. For mild-to-moderate pain, weak opioids such as tramadol, tapentadol, and codeine can be given in combination with nonopioid analgesics. We recommend morphine as the opioid of the first choice for moderate-to-severe cancer pain. Sustained-release formulations can be started 12 hourly, once the effective 24 h dose with immediate-release morphine is established. Opioid switch or rotation should be considered if there is inadequate analgesia or intolerable side effects. For opioid-induced respiratory depression, μ receptor antagonists (e.g., naloxone) must be used promptly. Antidepressants and/or anticonvulsants should be used to treat neuropathic cancer pain, and the dose should be titrated according to the clinical response and side effects. External beam radiotherapy should be offered to all patients with painful metastatic bone pain. There is evidence on use of ketamine in cancer neuropathic pain, but with no beneficial effect, thus, it is not recommended.

Efficacy of immediate-release oxycodone for dyspnoea in cancer patient: cancer dyspnoea relief (CDR) trial.

Guidelines recommend morphine as the first-line pharmacological treatment for cancer dyspnoea. However, trials with other opioids have not been performed. Our aim was to demonstrate the non-inferiority of oxycodone to morphine for relieving dyspnoea in cancer patients. We conducted a multicentre, open-label, parallel-group, randomized control trial. We randomly and equally assigned cancer patients on regular oxycodone who developed dyspnoea to get a single dose of oral immediate-release oxycodone or morphine. We evaluated the change in dyspnoea intensity (numeric rating scale: 0-10) and adverse events after the medication administration. This study was preconfidence interval -maturely terminated. All 17 enroled patients (8 using oxycodone, 9 using morphine) completed evaluations. In the oxycodone group, dyspnoea intensity decreased 1.75 points [95% confidence interval, 0.72-2.78] at 60 min and 1.50 points (95% confidence interval, -0.11 to 3.11) at 120 min. In the morphine group, dyspnoea decreased 1.33 points (95% confidence interval, 0.41-2.25) at 60 min and 1.00 point (95% confidence interval, -0.08 to 2.08) at 120 min. The differences did not fulfil the non-inferiority requirement. Although two and four patients in morphine group developed drowsiness at 60 and 120 min, no patient in oxycodone group developed significant adverse events. Although we did not show the non-inferiority of oxycodone, oxycodone may have some effectiveness for cancer dyspnoea without significant safety concern. UMIN-CTR: UMIN 000005760.

Safety profile of prophylactic rescue dosing of immediate-release oral opioids in cancer patients

BackgroundAppropriate prophylactic rescue dosing of opioids is considered effective for cancer pain relief, but no study has reported the safety of such prophylactic rescue. We compared the safety of prophylactic rescue dosing of immediate-release oral opioids with that of regular rescue dosing.MethodsThe study included 103 cancer patients who used either immediate-release morphine syrup or immediate-release oxycodone powder at Shizuoka Cancer Center between January and December 2016. Patients were divided into those who mostly used (prophylactic group) and those who never used (regular group) prophylactic rescue doses of opioids and compared the incidence of adverse events (AEs). We also investigated whether the prophylactic rescue dose negatively interfered with its objective activity, such as meals.ResultsIncidence of each AE in the prophylactic versus regular groups was as follows: somnolence, 20.6% versus 14.3%; nausea, 22.1% versus 17.1%; constipation, 19.1% versus 20.0%; urinary retention, 1.5% versus 2.9%; delirium, 4.4% versus 8.6%; and pruritus, 0% versus 2.9%. No serious AE associated with prophylactic rescue dosing was observed. No significant difference was observed in the incidence of any AE between the two groups (p > 0.05, Fisher’s exact test). No AE interfered with the objective activity of the prophylactic rescue dose.ConclusionIncidence of AEs associated with prophylactic rescue dosing is not different from that associated with regular rescue dosing. In addition, the prophylactic rescue dose did not adversely affect its objective activity, suggesting the safety of appropriate prophylactic rescue dosing was similar to that of regular rescue dosing.Trial registrationThe study approval number in the institution; H29-J30–29–1-3. Registered June 5, 2017.

Opioid Medications in Expensive Formulations Are Sold at a Lower Price than Immediate-Release Morphine in Countries throughout the World: Third Phase of Opioid Price Watch Cross-Sectional Study.

International Association for Hospice and Palliative Care implemented Opioid Price Watch (OPW) to monitor availability, dispensing prices and affordability of opioids. We found that opioids with complex delivery mechanisms [fentanyl transdermal (TD) patches, sustained-release (SR) morphine, and SR oxycodone] had lower dispensing prices than immediate-release (IR) morphine formulations. Identify the extent that SR and TD formulations are dispensed at lower prices than generic IR morphine and the possible reasons to explain this observation. Using OPW data for 30-day treatment Defined Daily Dosages, we identified where SR and TD formulations are dispensed at lower prices than IR morphine. Then we analyzed national lists of essential medicines (EML) in middle- and low-income countries to answer two questions: (1) Do they have opioids included? If yes, (2) Which ones? We then sought information on selection, budget allocation, and procurement for EML. OPW participants confirmed/verified the EML information. Eighteen countries reported higher dispensing prices for IR morphine (oral and/or injectable) than TD or SR formulation. Injectable morphine was highest in seven and lowest in two (range: $74-$742). SR morphine was the least expensive, while TD fentanyl was second. Median dispensing price for IR oral morphine was higher than SR morphine. The EML for 10 countries include opioids in TD and/or SR formulations. Opioids in expensive formulations are being favored over IR morphine both at the dispensing level and in their inclusion in national EML. Governments must take decisions based on efficacy, safety, and cost-effectiveness of medications.

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain

Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain. To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects. Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized. Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response. The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19). Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, -0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]). Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain. clinicaltrials.gov Identifier: NCT01583985.

How does controlled-release oxycodone compare with immediate-release oxycodone or controlled-release morphine for people with cancer-related pain?

How does controlled-release oxycodone compare with immediate-release oxycodone or controlled-release morphine for people with cancer-related pain?

The Contribution of the International Pain Policy Fellowship in Improving Opioid Availability in Georgia

In the Republic of Georgia, the incidence and prevalence of cancer are increasing, signifying a growing need for palliative care and pain relief, including with controlled opioid medicines. As a signatory to the Single Convention, the Georgian government has a responsibility to ensure the adequate availability of controlled medicines for medical purposes; however, the consumption of morphine is very low, suggesting a high occurrence of unrelieved pain. In Georgia, palliative care development began in the 2000s including the adoption of a policy document in 2005, the creation of the National Palliative Care Coordinator in 2006, and important changes in Georgian legislation in 2007 and 2008, which served to lay a foundation for improving opioid availability. In 2008, a neurologist from the Sarajishvili Institute of Neurology and Neurosurgery in Tbilisi, and member of the Georgia National Association for Palliative Care, was selected to be an International Pain Policy Fellow to focus on improving opioid availability. Working with colleagues, government officials, and international experts, the Fellow contributed to several improvements to opioid availability, such as 1) positive changes to opioid prescribing legislation, 2) clarification of legislative terminology regarding dependence syndrome, 3) initiating the importation of both sustained-release and immediate-release oral morphine, and 4) improvements in the availability of sustained-release morphine. Despite these varied achievements, morphine consumption remains low in Georgia relative to the estimated amounts needed. The Fellow is continuing to study and understand the barriers that are impeding physician's prescription of opioids and patient's acceptance of them.

(212) Reductions in postoperative pain intensity and opioid analgesia use with the bupivacaine-collagen matrix (INL-001) after open inguinal hernia repair

Clinical studies of the bioresorbable bupivacaine-collagen matrix (INL-001) have supported its safety and tolerability and found reductions in both selected measures of pain intensity (PI) and opioid analgesia use. It is currently in development for postoperative analgesia as part of multi-modal therapy for patients undergoing hernia repair. In 2 identical, Phase 3, multicenter, randomized, double-blind, placebo-controlled studies (MATRIX-1 and MATRIX-2), patients having elective open, tension-free inguinal hernia repair, with mesh, under general anesthesia were randomized to 300-mg bupivacaine HCl (ie, 3 INL-001 matrices) or 3 placebo matrices. Parenteral morphine was available in the immediate postsurgical period. When able to tolerate oral medication, patients began oral acetaminophen (650 mg tid) and were prescribed immediate-release morphine for breakthrough pain. Time-weighted sum of PI (SPI) and total use of opioid analgesia (TOpA) were determined through 72 hours after implantation. For each patient, the percentage difference of their rank for SPI from the mean rank for SPI and the percentage difference of their rank for TOpA from the mean rank for TOpA were obtained and the two percentage differences were summed with equal weight to create the integrated score (I-SPI-TOpA). Mean I-SPI-TOpA scores at 0-24 and 0-48 hours were significantly lower in the INL-001 group vs placebo for MATRIX-1, -2, and a pooled analysis of the 2 identical studies (P≤0.0237 for all). I-SPI-TOpA at 0-72 hours was significantly reduced for INL-001 vs placebo for MATRIX-2 as well as the pooled analysis (P≤0.0075 for both). Opioid-related treatment-emergent adverse events (TEAEs) were less common in the INL-001 group (16.6% INL-001, 28.4% placebo, P=0.0007). Overall rates of TEAEs were comparable between groups (62.3% INL-001, 68.8% placebo) most were mild or moderate and unrelated to treatment. These findings support the use of INL-001 as a long-acting, opioid-sparing analgesic for postoperative pain management. Funding provided by Innocoll, Inc.