OBJECTIVES: Opioids have shown consistent efficacy in neuropathic pain, but opioid-induced bowel dysfunction is a relevant problem. In controlled clinical trials, a fixed-dose combination of prolonged-release (PR) oxycodone/PR naloxone was superior to oxycodone alone in bowel function, while providing effective analgesia. The present report is an analysis of its efficacy and safety in a subgroup of patients with severe chronic neuropathic pain who were treated in a large observational study under real-life conditions.
RESEARCH DESIGN AND METHODS: Dosed according to pain severity, 1488 patients with chronic severe neuropathic pain received PR oxycodone/PR naloxone for up to 4 weeks. Variables included pain severity, patient-reported bowel function (Bowel Function Index; BFI) and quality of life.
RESULTS: During treatment with PR oxycodone/PR naloxone, mean pain intensity decreased in opioid-naive and opioid-pretreated patients. After 4 weeks on treatment, mean BFI scores were reduced from 41.6 ± 31.6 at the initiation visit to 16.5 ± 19.6 (p < 0.001), reflecting normal bowel function. Quality of life was improved by 47%.
CONCLUSIONS: Treatment of severe neuropathic pain with PR oxycodone/PR naloxone provided effective analgesia with the added benefit of favorable effects on bowel function and quality of life.
Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (<i>P</i> = .026) and the half-dose ER group both increased the number of breakthrough doses (<i>P</i> = .026) and had greater percent change in the total daily dose of breakthrough medication (<i>P</i> = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia. PERSPECTIVE: <i>In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.</i> (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: To determine the effect of a lower starting dose of OROS® hydromorphone compared with a higher starting dose.
DESIGN: Data from the first 15 days of treatment were compared in a combined analysis of three prospective, non-interventional studies.
SETTING: Non-interventional, carried out in daily routine settings.
PATIENTS: Patients had chronic severe pain due to osteoarthritis or from fragility fractures related to osteoporosis.
INTERVENTIONS: OROS-ANA-4001 and OROS-ANA-4002 had a daily starting dose of 8 mg of OROS® hydromorphone; OROS-ANA-4003 had a daily starting dose of 4 mg.
MAIN OUTCOME MEASURE(S): A post-hoc analysis to assess the effect of a low starting dose of OROS® hydromorphone on tolerability, pain control, and treatment satisfaction overall and for subgroups of opioid-naïve patients versus patients previously treated with opioids, and patients aged >65 years versus patients aged ≤65 years.
RESULTS: Treatment satisfaction and pain control improved in all studies; treatment satisfaction improved in a higher percentage of patients in the lower starting dose group. Gastrointestinal disorders were the most frequent treatment-emergent adverse events. Incidence of nausea was comparable between studies. Incidence of constipation, vomiting, fatigue, and pruritus was less frequent with the lower starting dose. In elderly and opioid-naïve patients, a lower starting dose was associated with lower overall incidence of adverse events, treatment-related adverse events, and those leading to discontinuation.
CONCLUSIONS: A lower starting dose was associated with better tolerability and a lower number of treatment terminations at a comparable level of pain control with high treatment satisfaction.
OBJECTIVE: To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain.
SETTINGS AND DESIGN: Multicenter, prospective, open-label, phase IV study.
PARTICIPANTS: Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP.
INTERVENTIONS: Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlled-release oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14.
MAIN OUTCOMES: BTP medication frequency on days 7 and 14, compared to baseline.
RESULTS: Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p > 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p > 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness.
CONCLUSION: Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.
Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in "pain on average" measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.
INTRODUCTION: Strong opioids are efficient drugs for treating chronic pain. In cancer patients, strong opioids are the mainstay of pain management, but in non-cancer pain caution is advised due to possible adverse effects, addictive potential and drug abuse.
AIMS: We studied the efficacy of OROS(®) hydromorphone in the treatment of chronic pain, the appearance and frequency of any adverse effects, the impact upon quality of life.
METHODS: Between April 2008 and May 2009 197 patients who received OROS hydromorphone for the treatment of severe chronic pain were monitored for 90 days. Seventy patients had cancer-related pain and 127 suffered pain due to non-malignant diseases, mostly degenerative joint disease.
RESULTS: During the monitoring period, the average pain score on the VAS scale fell from 8.1 to 3.3. A total of 70 adverse effects (AE) were reported and 17 patients stopped treatment due to these AE. The most frequent AEs included drowsiness, headache, vertigo, nausea, vomiting and constipation. According to patients, their quality of life greatly improved during the monitoring period.
CONCLUSION: The severity of patients' pain decreased during treatment with OROS hydromorphone with few adverse effects. The observed pain relief was accompanied by an improvement in the quality of the patients' lives.
ALO-01 (EMBEDA [morphine sulfate and naltrexone hydrochloride] extended-release capsules [King Pharmaceuticals, Inc, Bridgewater, NJ]), indicated for chronic moderate-to-severe pain, is designed to release naltrexone upon tampering (eg, by crushing), reducing morphine-induced subjective effects. This multicenter, randomized, double-blind, crossover study assessed pharmacokinetics, efficacy, and safety of ALO-01 and compared them with extended-release morphine sulfate (ERMS, KADIAN [morphine sulfate extended-release] capsules [Actavis US, Morristown, NJ]) in adults (N = 113) with osteoarthritis pain. Study periods included washout until pain flare (intensity ≥5, 0 to 10; 0 = no pain, 10 = worst pain); dose titration with ERMS (20 to 160mg BID); and randomization to 2 (crossover) 14-day treatment periods with ERMS or ALO-01, separated by 7 days of open-label ERMS. Assessments included pharmacokinetics (morphine, naltrexone), pain scores (0 to 10), Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; Patient Global Assessment of Medication (1 to 5; poor to excellent). Mean score at pain flare was 7.1. Morphine exposure from both formulations at steady state was similar. Plasma naltrexone concentrations were below limit-of-quantification for most patients and, when present, did not impact pain scores. During treatment, mean pain intensity (day 14: ERMS, 2.4; ALO-01, 2.3, <i>P</i> = .31), WOMAC change-from-baseline (mean pain, physical function, composite scores), and adverse event frequency were similar. ALO-01 and ERMS provided similar relief of osteoarthritis pain. PERSPECTIVE: We present data demonstrating that ALO-01 has steady-state morphine exposure, efficacy, and safety similar to marketed ERMS capsules. Results highlight the potential for morphine in ALO-01 to manage moderate-to-severe osteoarthritis pain, while the sequestered naltrexone does not interfere with efficacy. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
OBJECTIVE: The present randomized, double-blinded, crossover study compared the efficacy and safety of a seven-day buprenorphine transdermal system (BTDS) and placebo in patients with low back pain of moderate or greater seventy for at least six weeks. METHODS: Prestudy analgesics were discontinued the evening before random assignment to 5 µg/h BTDS or placebo, with acetaminophen 300 mg/codeme 30 mg, one to two tablets every 4 h to 6 h as needed, for rescue analgesia. The dose was titrated to effect weekly, if tolerated, to 10 µg/h and 20 µg/h BTDS. Each treatment phase was four weeks. RESULTS: Fifty-three patients (28 men, 25 women, mean [± SD] age 54-5 ± 12.7 years) were evaluable for efficacy (completed two weeks or more in each phase). Baseline pain was 62.1 ± 15.5 mm (100 mm visual analogue scale) and 2.5 ± 0.6 (five-point ordinal scale). BTDS resulted in lower mean daily pain scores than in the placebo group (37.6 ± 20.7 mm versus 43.6 ± 21 2 mm on a visual analogue scale, P = 0.0487; and 1.7 ± 0.6 versus 2.0 ± 0.7 on the ordinal scale, P = 0 0358) Most patients titrated to the highest dose of BTDS (59% 20 µg/h, 31% 10 µg/h and 10% 5 µg/h) There were improvements from baseline in pain and disability (Pain Disability Index), Pain and Sleep (visual analogue scale), Quebec Back Pain Disability Scale and Short-Form 36 Health Survey scores for both BTDS and placebo groups, without significant differences between treatments. While there were more opioid-related side effects with BTDS treatment than with placebo, there were no serious adverse events. A total of 82% of patients chose to continue BTDS in a long-term open-label evaluation, in whom improvements in pain intensity, functionality and quality of life were sustained for up to six months without analgesic tolerance. CONCLUSION: BTDS (5 µg/h to 20 µg/h) represents a new treatment option for initial opioid therapy in patients with chronic low back pain. (PsycInfo Database Record (c) 2025 APA, all rights reserved)
Opioids have shown consistent efficacy in neuropathic pain, but opioid-induced bowel dysfunction is a relevant problem. In controlled clinical trials, a fixed-dose combination of prolonged-release (PR) oxycodone/PR naloxone was superior to oxycodone alone in bowel function, while providing effective analgesia. The present report is an analysis of its efficacy and safety in a subgroup of patients with severe chronic neuropathic pain who were treated in a large observational study under real-life conditions.
RESEARCH DESIGN AND METHODS:
Dosed according to pain severity, 1488 patients with chronic severe neuropathic pain received PR oxycodone/PR naloxone for up to 4 weeks. Variables included pain severity, patient-reported bowel function (Bowel Function Index; BFI) and quality of life.
RESULTS:
During treatment with PR oxycodone/PR naloxone, mean pain intensity decreased in opioid-naive and opioid-pretreated patients. After 4 weeks on treatment, mean BFI scores were reduced from 41.6 ± 31.6 at the initiation visit to 16.5 ± 19.6 (p < 0.001), reflecting normal bowel function. Quality of life was improved by 47%.
CONCLUSIONS:
Treatment of severe neuropathic pain with PR oxycodone/PR naloxone provided effective analgesia with the added benefit of favorable effects on bowel function and quality of life.
