oxymorphone and Chronic-Disease

Opioids are recommended for control of moderate-to-severe, chronic, malignant, and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone has recently been launched. The aim of this review was to assess the effectiveness of oxymorphone as an analgesic in chronic pain. A systematic search for published studies of oral oxymorphone in the management of chronic pain was conducted. The studies were evaluated for their internal validity according to standard criteria. They were also evaluated for their external validity and research ethic aspects. A meta-analysis was performed to examine the effect of oxymorphone compared with placebo. Nine studies were evaluated; three were excluded because of low quality. Six controlled studies (duration 2-12 weeks) included a total of 1489 subjects suffering from chronic low back pain, chronic pain from osteoarthritis, and chronic cancer pain. Three of the studies were of high quality and three of medium quality. External validity was assessed to be high, medium, and low (in one, three, and two studies, respectively). The meta-analysis suggests that daily doses of 40-100mg are superior to placebo; however, the estimate (reduction of pain intensity compared with placebo) of the treatment effect is imprecise (95% confidence interval -17.08, -8.69). Limited evidence suggests that oxymorphone is effective for pain control in patients with cancer. No significant differences between oxymorphone and oxycodone at equipotent doses were found. In conclusion, oxymorphone is superior to placebo. There is no evidence that the efficacy of oxymorphone differs from other opioids.

Topics: Analgesics, Opioid; Chronic Disease; Humans; Low Back Pain; Neoplasms; Osteoarthritis; Oxymorphone; Pain; Randomized Controlled Trials as Topic

Opana ER (oxymorphone extended release [ER]) is a new oral long-acting formulation indicated for the treatment of moderate to severe chronic pain. Because the ER matrix slowly releases oxymorphone over 12 h, consistent plasma levels are produced with low peak-to-trough fluctuations. Oxymorphone ER is the only long-acting opioid that contains oxymorphone, which exhibits some distinct pharmacologic properties compared with most other opioids, including a longer half-life, higher affinity for the micro-opioid receptor, and lack of interaction with the CYPP450 drug-metabolizing system. With a safety and tolerability profile similar to other opioids and documented efficacy in several models of chronic pain (low back, cancer, and osteoarthritis), oxymorphone ER provides a new option for clinicians and patients in the treatment of chronic pain.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Chronic Disease; Delayed-Action Preparations; Drug and Narcotic Control; Humans; Oxymorphone; Pain; Patient Selection; Severity of Illness Index; Treatment Outcome

Opioid-experienced (N = 250) patients with chronic, moderate to severe low back pain (LBP) were converted from their prestudy opioid(s) to an approximately equianalgesic dose of OPANA ER (oxymorphone extended release). Patients continued slow titration, with 56% stabilized within 1 month to a dose of OPANA ER that reduced average pain to <40 mm on a visual analog scale with good tolerability. Stabilized patients (n = 143) were randomized to placebo or their stabilized dose of OPANA ER every 12 hours for a 12-week double-blind period. Pain intensity increased significantly more for patients randomized to placebo than for patients who continued their stabilized dose of OPANA ER; the increase from baseline (at randomization) to final visit was 31.6 mm for placebo versus 8.7 mm with OPANA ER (P < .0001). During double-blind treatment, placebo patients were approximately 8-fold more likely than OPANA ER patients to discontinue because of lack of efficacy (P < .001). Discontinuations as a result of adverse events were similar between groups, 10% with placebo and 11% with OPANA ER. Opioid-related adverse events included constipation (6%), somnolence (3%), and nausea (3%). Fifty-seven percent of opioid-experienced patients with chronic, moderate to severe LBP achieved a stable dose of OPANA ER that was efficacious and generally well-tolerated for up to 12 weeks.. In a 12-week, double-blind, randomized, placebo-controlled trial in opioid-experienced patients with chronic, moderate to severe LBP, OPANA ER provided efficacious, long-term analgesia and was generally well-tolerated. OPANA ER may provide clinicians with a new treatment option for patients experiencing suboptimal analgesic responses or poor tolerability with other opioids.

Topics: Adult; Analgesics, Opioid; Chronic Disease; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Morphine Derivatives; Oxymorphone; Pain Measurement; Patient Satisfaction; Placebos; Severity of Illness Index; Treatment Outcome

This multicenter, randomized, double-blind, placebo- and active-controlled trial was conducted to compare the analgesic efficacy and safety of oxymorphone extended release (ER) with placebo and oxycodone controlled release (CR) in ambulatory patients with moderate to severe chronic low back pain requiring opioid therapy. Patients (N = 213) aged 18 to 75 years were randomized to receive oxymorphone ER (10 to 110 mg) or oxycodone CR (20 to 220 mg) every 12 hours during a 7- to 14-day dose-titration phase. Patients achieving effective analgesia at a stable opioid dose entered an 18-day double-blind treatment phase and either continued opioid therapy or received placebo. With stable dosing throughout the treatment phase, oxymorphone ER (79.4 mg/day) and oxycodone CR (155 mg/day) were superior to placebo for change from baseline in pain intensity as measured on a visual analog scale; the LS mean differences were -18.21 and 18.55 (95% CI, -25.83 to -10.58 and -26.12 to -10.98, respectively; P = .0001). Use of rescue medication was 20 mg per day. Adverse events for the active drugs were similar; the most frequent were constipation and sedation. Oxymorphone ER and oxycodone CR were generally safe and effective for controlling low back pain. Oxymorphone ER was equianalgesic to oxycodone CR at half the milligram daily dosage, with comparable safety.. Definitive studies of long-acting opioids in patients with chronic low back pain are lacking. We report the results of a multicenter, randomized, placebo-controlled, double-blind study evaluating the analgesic efficacy and safety of oxymorphone ER and oxycodone CR in opioid-experienced patients with chronic low back pain.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Chronic Disease; Constipation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Low Back Pain; Male; Middle Aged; Oxycodone; Oxymorphone; Pain Measurement; Placebo Effect; Placebos; Sleep Stages; Treatment Outcome

Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release (CR) and immediate-release (IR) oxycodone. In open-label titration (2 to 21 days), these patients were stabilized on IR oxycodone qid. They were then randomized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose. Mean (+/- SD) pain intensity (0 = none to 10 = severe) decreased from a baseline of 6.0 +/- 2.2 to 2.7 +/- 1.1 after titration with IR oxycodone dosed qid. Pain intensity remained stable throughout double-blind treatment: 2.7 +/- 1.9 with CR oxycodone and 2.8 +/- 1.9 with IR oxycodone. Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications (IR and CR oxycodone). Adverse events were similar for both formulations. Following repeat dosing under double-blind conditions, oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Biological Availability; Chronic Disease; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphinans; Neoplasms; Oxycodone; Oxymorphone; Pain; Pain Measurement; Therapeutic Equivalency; Vomiting

Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking.. We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis.. Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased.. While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.

Topics: Adult; Analgesics, Opioid; Chronic Disease; Chronic Pain; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Morphinans; Oxycodone; Oxymorphone; Renal Dialysis

The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists.. To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER.. The main outcome measure for the analysis was DACON. Pharmacy and medical claims data from a large commercially insured population (i3 InVision Data Mart database) were analyzed to identify patients with at least 1 pharmacy claim for either oxycodone CR or oxymorphone ER from July 1, 2007, to September 30, 2009. After an initial 30-day titration period, all subjects included in the study had 1 or more claims totaling at least a 90-day supply of either study drug during the subsequent 90 days (DACON measurement period). Patients were excluded if there was evidence of a switch from one to the other study opioid during the 90-day measurement period. There were no limitations on the use of other opioids, either short- or long-acting, during either the DACON measurement period or the previous 6 months (baseline period). In addition, patients were excluded if the enrollee was younger than 18 years old, pregnant, did not have continuous insurance coverage for the 6 months before and after the start of the 90-day DACON measurement, or were enrolled in an HMO plan. Bivariate analyses were performed with between-group differences in DACON values assessed using t-tests and Wilcoxon rank sum tests. Patient characteristics including age, sex, geographic location, and baseline Charlson Comorbidity Index (CCI) for each drug group were evaluated descriptively using either the Pearson chi-square test or t-test. Multivariate analyses were conducted using generalized linear models (GLM) to adjust for the observed heterogeneity among patients in the observational database. For the GLMs, the gamma distribution and log link function were chosen to account for non-normal distributions of DACON. Independent variables included study drug, tablet strengths, age, sex, CCI, the maximum days gap between prescription refills during the DACON measurement period, and other opioid medication use. Several sensitivity analyses were conducted to verify all findings.. The final analyses were conducted on 6,567 oxycodone CR patients and 796 oxymorphone ER patients. The unadjusted DACON mean value for the highest strength of oxycodone CR 80 milligrams (mg) was 3.9, compared with 2.9 for oxymorphone ER 40 mg (P < 0.001); mean DACON values were 3.0 versus 2.4, respectively, for lower strengths (P < 0.001) and 3.1 versus 2.5 for all strengths (P < 0.001). After adjusting for age, sex, CCI, maximum gap days, and other opioid medication use, a risk-adjusted mean difference in DACON remained, with oxycodone CR patients receiving on average 0.6 tablets more per day than those dispensed oxymorphone ER (P < 0.001). The direction, magnitude, and statistical significance of these differences were essentially unchanged in sensitivity analyses.. On average during a 90-day time period, patients taking oxymorphone ER consumed 0.6 fewer tablets per day than did patients taking oxycodone CR. Further research is necessary to see if this difference amounts to cost savings for health plans that provide prescription reimbursement for patients with chronic pain syndromes.

Topics: Administration, Oral; Analgesics, Opioid; Chi-Square Distribution; Chronic Disease; Cost Savings; Delayed-Action Preparations; Drug Costs; Drug Prescriptions; Drug Utilization Review; Female; Humans; Insurance, Pharmaceutical Services; Linear Models; Male; Managed Care Programs; Middle Aged; Multivariate Analysis; Oxycodone; Oxymorphone; Pain; Practice Patterns, Physicians'; Retrospective Studies; Tablets; Time Factors; United States

To evaluate the influence of age, sex, and previous opioid experience on the likelihood of successfully titrating opioid-naive and experienced patients with chronic low back pain (CLBP) to an effective and well-tolerated dose of oxymorphone extended release (ER).. Post hoc analysis of open-label titration phases of two enriched-enrollment randomized-withdrawal phase III trials in 575 adults with moderate-to-severe CLBP. Opioid-naive patients (n = 325) initiated oxymorphone ER at 10 mg/day (5 mg q12 h). Opioid-experienced patients (n = 250) initiated at a dose equianalgesic to their previous opioid and were allowed doses of 5 mg oxymorphone immediate-release rescue medication every 4-6 h, as needed. Oxymorphone ER was gradually titrated to a dose that reduced pain to or=65 years were less likely than patients aged <65 years to complete titration (45 vs. 63%; p = 0.002; 95% CI, -0.30 to -0.06) and more likely to discontinue owing to adverse events (40 vs. 15%; p < 0.001; 95% CI, 0.14-0.36). Oxycodone-experienced patients were less likely than hydrocodone-experienced patients to complete titration (46 vs. 62%, p = 0.03; 95% CI,-0.30 to -0.02). Among successfully titrated patients, pain decreased regardless of prior opioid therapy, sex, or age.. Most patients with CLBP were titrated to an effective, generally well-tolerated oxymorphone ER dose. Older patients and those converted from oxycodone may require more gradual titration. A study limitation is that patients initiated oxymorphone ER to comply with protocol, whereas treatment failure typically motivates opioid initiation or switching in clinical practice.

Topics: Aged; Analgesics, Opioid; Chronic Disease; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Hydromorphone; Low Back Pain; Male; Middle Aged; Oxycodone; Oxymorphone; Pain Measurement; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome

This study assessed the potential effects of age, sex, and prior opioid use on the response to oxymorphone extended release (ER) in patients with moderate to severe chronic low back pain.. Combined data from 2 placebo-controlled clinical trials with an enriched-enrollment, randomized-withdrawal design were analyzed. In patients aged > or =18 years with chronic low back pain, the dose of oxymorphone ER was titrated to a stable, tolerable, effective dose. Patients who completed titration were randomly assigned to a 12-week double-blind study period with oxymorphone ER or placebo. Oxymorphone immediate release 5 mg was permitted q4-6h, as needed for rescue medication or withdrawal symptoms, for 4 days after randomization and restricted to 10 mg/d thereafter. Pain intensity (100-mm visual analog scale [VAS]; 0 = no pain to 100 = worst pain imaginable) and time to study discontinuation due to lack of efficacy were compared with stratification by age (<65 vs > or =65 years), sex, and prior opioid use. Adverse events were categorized by severity and relation to study medication.. Of 575 patients, 348 completed titration and 347 entered the double-blind study phase. There were no significant between-group differences in demographic variables, except that the mean age in the oxymorphone ER group was significantly higher (P = 0.04), and the proportion of men was significantly lower (P = 0.01). There was no significant age difference between the oxymorphone ER and placebo groups stratified by age (<65 vs > or =65 years). Fewer patients aged > or =65 years versus <65 years completed titration (45.0% [36/80] vs 63.0% [312/495]; P = 0.002). The least-squares mean (SEM) differences in VAS pain scores between the oxymorphone ER (n = 174) and placebo (n = 169) groups were significant at each postbaseline assessment (P < 0.001) and at study completion (12.3 [2.8] mm; P < 0.001) and was not significantly affected by age, sex, or prior opioid use. Age and sex had no significant influence on adverse events or discontinuations due to lack of efficacy. More discontinuations due to lack of efficacy occurred among patients in the placebo group (hazard ratio, 5.01; P < 0.001) and among opioid-experienced patients. The latter effect was limited to opioid-experienced patients who received placebo. The rates of discontinuation due to lack of efficacy were similar between oxymorphone ER-treated opioid-naive and opioid-experienced patients (11.4% vs 11.6%). The proportion of patients who experienced opioid-related adverse events was significantly greater in the oxymorphone ER group compared with the placebo group (25.7% vs 16.3%; P = 0.03). The most frequent treatment-emergent adverse events in the oxymorphone ER group were nausea (8.0%), constipation (6.3%), vomiting (4.6%), and diarrhea (4.0%); in the placebo group were nausea (5.8%), diarrhea (4.7%), and increased sweating (2.3%).. In the enriched population of patients who successfully titrated to oxymorphone ER, oxymorphone ER was effective and generally well tolerated, independent of patients' age, sex, or previous opioid use.

Topics: Age Factors; Aged; Analgesics, Opioid; Chronic Disease; Delayed-Action Preparations; Double-Blind Method; Female; Follow-Up Studies; Humans; Low Back Pain; Male; Middle Aged; Oxymorphone; Pain Measurement; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Sex Factors

Topics: Analgesics, Opioid; Cannabidiol; Cannabinoids; Carbazoles; Chronic Disease; Dronabinol; Drug Combinations; Humans; Ibuprofen; Oxycodone; Oxymorphone; Pain; Plant Extracts; Serotonin Receptor Agonists; Tryptamines

Despite the increasing popularity of intrathecal infusions to treat patients with long-term non-cancer-related pain, this therapy is not without serious side-effects. Five out of 23 patients who had intrathecal infusions of opiates for longer than 24 months developed leg and feet edema. As predisposing factors, cardiovascular disease, deep venous thrombosis, peripheral vascular disease, and venous stasis of the lower extremities were considered. Every patient who developed pedal and leg edema after the implantation of an infusion pump was also found to have leg edema and venous stasis prior to the time when the pump was inserted. This complication was severe enough to limit their physical activity, and to produce lymphedema, ulcerations and hyperpigmentation of the skin. Reduction of the edema occurred when the dose of the opiate was decreased, and in two cases in which the infusion was discontinued, there was almost complete resolution of the syndrome. It appears that the pre-existence of pedal edema and of venous stasis is a relative contraindication to the long-term intrathecal infusion of opiates in patients with chronic non-cancer pain.

Topics: Arachnoiditis; Causality; Chronic Disease; Comorbidity; Contraindications; Edema; Foot; Hyperpigmentation; Incidence; Infusion Pumps, Implantable; Injections, Spinal; Leg; Lymphedema; Morphine; Narcotics; Oxymorphone; Pseudarthrosis; Retrospective Studies; Skin; Venous Insufficiency