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Harry Ahdieh - One of the best experts on this subject based on the ideXlab platform.
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Long-term tolerability and effectiveness of Oxymorphone extended release in patients with cancer.
Journal of opioid management, 2010Co-Authors: Neal E. Slatkin, Errol M. Gould, Rn Michelle I. Rhiner, Harry AhdiehAbstract:To evaluate the long-term safety, tolerability, and effectiveness of Oxymorphone extended release (ER) in patients with cancer-related pain. Post hoc analysis of two-1-year open-label extension studies. Multiple US cancer treatment facilities. Patients with cancer pain who had participated in two short-term crossover comparator trials of Oxymorphone ER: one open-label and one double-blind randomized. Patients who had been taking Oxymorphone ER continued the dose established in the previous study. Patients who had been taking a comparator opioid were switched to an equianalgesic dose of Oxymorphone ER. All patients underwent individualized Oxymorphone ER dose titration to optimize effectiveness and tolerability. Current, average, worst, and least pain scores were normalized to a 100-point scale. Patients rated treatment on a five-point global assessment of study medication (Poor = 1 to Excellent = 5). All adverse events (AEs) were recorded. Of the 80 patients who entered the extension trials, 26 completed 52 weeks, 7 discontinued owing to loss of effectiveness, and 20 discontinued owing to AEs, most of which were unrelated to study drug. No significant increase in mean (standard deviation [SDD average pain intensity was observed from baseline (30.5 [19.6], 100-point scale) to final visit (35.9 [21.1], p = 0.37). The most common AEs were concomitant disease progression (28.8 percent, n=23), nausea (22.5 percent, n=18), dyspnea (16.3 percent, n=13), fatigue (16.3 percent, n=13), and edema of the lower limb (15 percent, n=12). In these patients with pain related to cancer, Oxymorphone ER was generally well tolerated and provided stable long-term pain control.
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titration with Oxymorphone extended release to achieve effective long term pain relief and improve tolerability in opioid naive patients with moderate to severe pain
Pain Medicine, 2008Co-Authors: Richard Rauck, Rosemary Kerwin, Harry AhdiehAbstract:Objective. Assess the effectiveness and tolerability of a program of gradual dose titration with Oxymorphone extended release (ER) for treatment of moderate to severe chronic pain in opioid-naive patients. Design. Open-label, nonrandomized 6-month study with a titration/stabilization period of ≤1 month followed by a 5-month maintenance period. Setting. Multidisciplinary pain centers in the United States. Patients. Adult opioid-naive patients with moderate to severe chronic pain. Interventions. Patients were gradually titrated from a 5-mg dose of Oxymorphone ER (taken every 12 hours) to a stabilized dose that provided effective pain relief and was well tolerated. Outcome Measures. Brief Pain Inventory Short Form questions 5 and 9, patient and physician global assessments of pain relief, adverse events (AEs), and discontinuations. Results. The majority (94/126; 75%) of patients were stabilized on a dose of Oxymorphone ER that provided effective pain relief with tolerable AEs. Most (81/94; 86%) required 50%) reductions of pain interference with quality-of-life measures. There was minimal dose escalation over the 5 months and low use of rescue medication. Conclusions. Oxymorphone ER provided effective pain relief from moderate to severe chronic pain in opioid-naive patients. Gradual titration was well tolerated, with a low rate of discontinuations caused by AEs.
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efficacy and tolerability of Oxymorphone immediate release for acute postoperative pain after abdominal surgery a randomized double blind active and placebo controlled parallel group trial
Clinical Therapeutics, 2007Co-Authors: Keith Aqua, Harry Ahdieh, Joseph Gimbel, Neil Singla, Rosemary KerwinAbstract:Abstract Background: Patients are typically switched from parenteral opioids to oral opioids during the 24 to 48 hours after surgery. In June 2006, an oral immediate-release (IR) tablet formulation of Oxymorphone was approved for the treatment of acute moderate to severe pain. Single doses of Oxymorphone IR have been reported to provide significant pain relief after orthopedic surgery. Objective: This study assessed the efficacy and tolerability of multiple fixed doses of Oxymorphone IR in the treatment of acute postoperative pain after abdominal surgery. Methods: This was a multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group study in men and women aged ≥18 years undergoing abdominal surgery that required a ≥3-cm incision. Patients who discontinued short-acting parenteral opioids and developed moderate or severe pain (4-point categorical scale [none, mild, moderate, or severe] and pain intensity ≥50 mm on a 100-mm visual analog scale [from 0=no pain to 100=worst pain imaginable]) within 30 hours after abdominal surgery were randomized to receive Oxymorphone IR 10 or 20 mg, oxycodone IR 15 mg, or placebo every 4 to 6 hours after the previous dose. The study included 2 efficacy assessments: a single-dose evaluation for up to 6 hours after the dose, and a multipledose evaluation for up to 48 hours after the first dose. Pain was assessed at 15-minute intervals during the hour after the first dose, hourly thereafter for the next 5 hours, and before each subsequent dose. The primary efficacy end point was the median time to study discontinuation for all causes. Assessment of tolerability was based on the proportion of study discontinuations due to treatment-emergent adverse events (AEs). Results: Three hundred thirty-one patients were included in the study. Demographic characteristics were similar across all groups: 98.8% (327) of patients were women, and 80.1% (265) of the abdominal surgeries were hysterectomies. The mean (SD) age of the study population was 42.6 (9.3) years. The median time to study discontinuation for all causes was significantly longer for all active treatments compared with placebo (Oxymorphone IR 10 mg, 17.9 hours; Oxymorphone IR 20 mg, 20.3 hours; oxycodone IR 15 mg, 24.1 hours; placebo, 4.8 hours; P P P P P P = NS). The fixed-dose design was a study limitation, as it did not allow titration to effect and thus did not mirror clinical practice. Conclusion: In this predominantly female population undergoing abdominal surgery, Oxymorphone IR given every 4 to 6 hours for up to 48 hours provided efficacious and tolerable analgesia for moderate to severe pain.
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A 12-week, randomized, placebo-controlled trial assessing the safety and efficacy of Oxymorphone extended release for opioid-naive patients with chronic low back pain
Current medical research and opinion, 2006Co-Authors: Nathaniel P. Katz, Harry Ahdieh, Richard Rauck, Roland Gerritsen Van Der Hoop, Rosemary Kerwin, Gilbert PodolskyAbstract:ABSTRACTObjective: Determine the efficacy and tolerability of Oxymorphone extended release (OPANA ER) in opioid-naive patients with moderate to severe chronic low back pain (CLBP).Design and methods: Patients ≥ 18 years of age were titrated with Oxymorphone ER (5- to 10‑mg increments every 12 h, every 3–7 days) to a well-tolerated, stabilized dose. Patients were then randomized to continue their Oxymorphone ER dose or receive placebo every 12 h for 12 weeks. Oxymorphone immediate release was available every 4–6 h, as needed, for the first 4 days and twice daily thereafter.Results: Sixty-three percent of patients (205/325) were titrated to a stabilized dose of Oxymorphone ER, most (203/205) within 1 month. During titration, 18% discontinued from adverse events (AEs) and 1% from lack of efficacy. For patients completing titration, average pain intensity decreased from 69.4 mm at screening to 22.7 mm ( p < 0.0001). After randomization, 68% of Oxymorphone ER and 47% of placebo patients completed 12 weeks of ...
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A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of Oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee.
Clinical therapeutics, 2006Co-Authors: Alan J. Kivitz, Harry Ahdieh, Bradley S. GalerAbstract:Abstract Background: Oxymorphone extended release (ER) is a tablet formulation of the μ-opioid agonist Oxymorphone designed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period. Objective: This study compared the analgesic efficacy, dose response, and tolerability of 3 doses of Oxymorphone ER given every 12 hours with those of placebo in patients with pain related to osteoarthritis (OA) of the hip or knee. Methods: This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, Phase III trial. Patients with OA of the hip or knee who were receiving an opioid medication for chronic, moderate to severe pain or who were judged by the investigator to have received suboptimal analgesia with nonopioid analgesics entered a 2- to 7-day washout of analgesic medication. When pain in the index joint was >40 mm on a 100-mm visual analog scale (VAS), patients were randomized to receive 1 of 4 regimens: Oxymorphone ER 10 mg q12h during weeks 1 and 2; Oxymorphone ER 20 mg q12h in week 1 and 40 mg q12h in week 2; Oxymorphone ER 20 mg q12h in week 1 and 50 mg q12h in week 2; or placebo q12h during weeks 1 and 2. The primary end point was the change in VAS score for arthritis pain intensity. Other assessments included the Western Ontario and McMaster Universities (WOMAC) OA Index subscales for pain, stiffness, and physical function and the composite index; the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical health component summary (PCS) score; the Chronic Pain Sleep Inventory (CPSI) score; vital signs; clinical laboratory parameters; and adverse events (AEs). AEs were recorded at each clinic visit. Results: Three hundred seventy patients were randomizedto treatment (95 Oxymorphone ER 10 mg, 93 Oxymorphone ER 40 mg, 91 Oxymorphone ER 50 mg, and 91 placebo), and 198 completed the study. Least squares mean changes from baseline in the VAS arthritis pain intensity score were −21, −28, −29, and −17 mm in the Oxymorphone ER 10, 40, and 50 mg and placebo groups, respectively ( P = 0.002, modified Tukey linear trend test). Oxymorphone ER 40 and 50 mg produced significant improvements from baseline compared with placebo in the WOMAC subscale scores for pain (least squares mean change: −85.1, −108.0, and −42.5, respectively; P ≤ 0.025 for 40 mg, P ≤ 0.001 for 50 mg), stiffness (−40.5, −48.1, and −17.0; both, P ≤ 0.001), and physical function (−256.8, −310.8, and −116.5; P ≤ 0.01 and P ≤ 0.001, respectively); the SF-36 PCS score (4.6, 3.6, and −0.1; P P P ≤ 0.025) and physical function subscales (−232.9; P ≤ 0.025) and the SF-36 PCS score (3.9; P Conclusion: In these patients with chronic, moderate to severe pain related to OA of the hip or knee, Oxymorphone ER administered twice daily for 2 weeks produced dose-related reductions in arthritis pain intensity and improvements in physical function.
Richard C Dart - One of the best experts on this subject based on the ideXlab platform.
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scoring the best deal quantity discounts and street price variation of diverted oxycodone and Oxymorphone
Pharmacoepidemiology and Drug Safety, 2019Co-Authors: Jacob A Lebin, David L Murphy, Stevan G Severtson, Gabrielle E Bau, Nabarun Dasgupta, Richard C DartAbstract:PURPOSE Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and Oxymorphone. METHODS A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and Oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. RESULTS A total of 5611 oxycodone and 1420 Oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for Oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and Oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. CONCLUSION Street prices for diverted oxycodone and Oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.
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Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and Oxymorphone.
Pharmacoepidemiology and drug safety, 2018Co-Authors: Jacob A Lebin, David L Murphy, Stevan G Severtson, Gabrielle E Bau, Nabarun Dasgupta, Richard C DartAbstract:PURPOSE Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and Oxymorphone. METHODS A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and Oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. RESULTS A total of 5611 oxycodone and 1420 Oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for Oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P
William D. Fiske - One of the best experts on this subject based on the ideXlab platform.
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Original Research
2013Co-Authors: Bioequivalence Of Oxymorphone, Qinfang Xiang, Irma H Benedek, William D. Fiske, Endo Pharmaceuticals IncAbstract:extended release and crush-resistant Oxymorphone extended releas
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The Effects of Ethanol on the Bioavailability of Oxymorphone Extended-Release Tablets and Oxymorphone Crush-Resistant Extended-Release Tablets
The journal of pain : official journal of the American Pain Society, 2012Co-Authors: William D. Fiske, Janet Jobes, Qinfang Xiang, Souchan Chang, Irma H BenedekAbstract:Adverse events may occur with an extended-release (ER) opioid if tampering or coadministration with ethanol causes excessive exposure (dose dumping) to the opioid. The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of Oxymorphone ER and Oxymorphone crush-resistant formulation (CRF) were evaluated. In vitro dissolution rates were measured for Oxymorphone ER 40-mg and Oxymorphone CRF 40-mg tablets in aqueous solutions of 0 to 40% ethanol. In 2 in vivo, open-label, randomized, crossover studies, fasted healthy volunteers received single oral doses of Oxymorphone ER 40 mg or Oxymorphone CRF 40 mg with 240 mL of 0 to 40% ethanol. Naltrexone was used to minimize opioid effects. In the in vitro analyses, dissolution rates of Oxymorphone ER and CRF were unaffected in aqueous solutions of ≤40% ethanol. Coadministration of Oxymorphone ER or Oxymorphone CRF with ethanol 20 and 40% increased Oxymorphone peak plasma concentrations (C(max)) by 14 to 80% and reduced time to C(max). For both formulations, Oxymorphone area under the curve and terminal half-life were largely unaffected, but C(max) increased with ethanol dose. Neither Oxymorphone formulation exhibited dose dumping in terms of overall exposure when coingested with ethanol. Administering Oxymorphone ER or Oxymorphone CRF with 240 mL of ≤40% ethanol increased Oxymorphone C(max) without dose dumping in terms of area under the curve. These results provide reassurance about the integrity of Oxymorphone ER formulations with ethanol. Nonetheless, alcohol and opioids should never be combined because of the risk of respiratory depression. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
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Bioequivalence of Oxymorphone extended release and crush-resistant Oxymorphone extended release
Drug design development and therapy, 2011Co-Authors: Irma H Benedek, Janet Jobes, Qinfang Xiang, William D. FiskeAbstract:A formulation of crush-resistant extended-release opioids may deter abuse. The purpose of this study was to evaluate the bioequivalence of Oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of Oxymorphone extended-release (Oxy-CRF). In three open-label, randomized studies, healthy adults at a clinical research center received two single oral doses of Oxy-ER and two single doses of Oxy-CRF, each separated by a ≥7-day washout. Doses were administered under fasted conditions (study 1, 5 mg doses; study 2, 40 mg doses) or after a high-fat breakfast (study 3, 40 mg doses). Subjects administered 40 mg doses also received naltrexone. The primary endpoint was systemic Oxymorphone exposure; the bioequivalence criterion was met if the 90% confidence intervals of the geometric mean ratio (Oxy-CRF/Oxy-ER) for Oxymorphone area under the curve from time 0 to the last measured concentration (AUC(0-t)), AUC from time 0 to infinity (AUC(0-inf)), and maximum plasma concentration (C(max)) were within 0.8-1.25. Safety was assessed by monitoring adverse events. In studies 1, 2, and 3, the safety population comprised 30, 37, and 36 subjects and the pharmacokinetics population comprised 27, 30, and 29 subjects, respectively. Oxy-ER and Oxy-CRF produced similar mean ± standard deviation Oxymorphone AUC(0-t) (study 1, 5.05 ± 1.55 versus 5.29 ± 1.52 ng · h/mL; study 2, 31.51 ± 10.95 versus 31.23 ± 10.33 ng · h/mL; study 3, 50.16 ± 14.91 versus 49.01 ± 14.03 ng · h/mL) and C(max) (0.38 ± 0.11 versus 0.37 ± 0.12 ng/mL; 2.37 ± 1.20 versus 2.41 ± 0.94 ng/mL; 5.87 ± 1.99 versus 5.63 ± 2.26 ng/mL) under all conditions. The 90% confidence intervals for plasma Oxymorphone AUC(0-t), AUC(0-inf), and C(max) fulfilled the bioequivalence criterion. Adverse event rates were similar with Oxy-ER and Oxy-CRF (study 1, 25% versus 23%; study 2, 9% versus 16%; study 3, 20% each group). Oxy-CRF and Oxy-ER (5 mg and 40 mg) are bioequivalent under fasted and fed conditions, suggesting that Oxy-CRF will have clinical efficacy and safety equivalent to Oxy-ER.
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bioequivalence of Oxymorphone extended release and crush resistant Oxymorphone extended release
Drug Design Development and Therapy, 2011Co-Authors: Irma H Benedek, Janet Jobes, Qinfang Xiang, William D. FiskeAbstract:Background A formulation of crush-resistant extended-release opioids may deter abuse. The purpose of this study was to evaluate the bioequivalence of Oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of Oxymorphone extended-release (Oxy-CRF).
Errol M. Gould - One of the best experts on this subject based on the ideXlab platform.
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An open-label pharmacokinetic study of Oxymorphone extended release in the presence of naltrexone in the older adult.
Journal of opioid management, 2012Co-Authors: Joseph V. Pergolizzi, Robert B. Raffa, Robert Taylor, Swati Nagar, Sumedha A. Labhsetwar, Nicholas R. Stc. Sinclair, Errol M. GouldAbstract:The aging population generally has greater need for analgesics and is best served by having as many good therapeutic options as possible. Geriatric analgesia requires special consideration of age-associated physiologic changes that can affect drug dosing. The study of extended-release (ER) Oxymorphone in older (≥ 65 years of age) versus younger (18-40 years of age) male and female volunteers was described. In this multiple-dose, parallel-group, open-label trial, healthy volunteers received a single oral dose of 20 mg Oxymorphone ER on day 1, followed by a 48-hour washout period, then two oral doses of 20 mg Oxymorphone ER tablets every 12 hours from day 3 to day 8, and a single oral dose of 20 mg Oxymorphone ER on day 9. Naltrexone was administered each day to the subjects. The elderly had significantly higher plasma levels of Oxymorphone, 6-OH-Oxymorphone, and Oxymorphone-3-glucuronide than the younger group (1.36-fold higher area under the concentration versus time curve [AUC] and 1.45-fold higher C(max)) when they were treated with a single dose (20 mg) of Oxymorphone. Steady-state AUC and C(max) also were higher in the older group. Following adjustment for body weight, AUC values for Oxymorphone and its metabolites were about 40 percent higher and the mean C(max) values were 30-35 percent higher in the older group compared to the younger group. The results of the current study of an ER formulation revealed no pharmacokinetic features that would preclude dosing in the elderly. As with any drug and any age group (but particularly the elderly), Oxymorphone ER should be initiated at lower doses in elderly compared to younger patients and titrated to optimal level.
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Factors affecting acceptability of titrated Oxymorphone extended release in chronic low back pain - an individual patient analysis.
Current medical research and opinion, 2010Co-Authors: John H. Peniston, Qinfang Xiang, Errol M. GouldAbstract: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=40 mm on a 100 mm visual analog scale. NCT00225797, NCT00226421. Number of patients reaching stabilized Oxymorphone ER dose, reasons for treatment discontinuation in patients not reaching stabilized dose. Open-label titration was successful in 61% (348/575) of patients, and similar proportions of men (63%) and women (59%) and opioid-naive (63%) and experienced (57%) patients. Patients aged >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.
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Long-term tolerability and effectiveness of Oxymorphone extended release in patients with cancer.
Journal of opioid management, 2010Co-Authors: Neal E. Slatkin, Errol M. Gould, Rn Michelle I. Rhiner, Harry AhdiehAbstract:To evaluate the long-term safety, tolerability, and effectiveness of Oxymorphone extended release (ER) in patients with cancer-related pain. Post hoc analysis of two-1-year open-label extension studies. Multiple US cancer treatment facilities. Patients with cancer pain who had participated in two short-term crossover comparator trials of Oxymorphone ER: one open-label and one double-blind randomized. Patients who had been taking Oxymorphone ER continued the dose established in the previous study. Patients who had been taking a comparator opioid were switched to an equianalgesic dose of Oxymorphone ER. All patients underwent individualized Oxymorphone ER dose titration to optimize effectiveness and tolerability. Current, average, worst, and least pain scores were normalized to a 100-point scale. Patients rated treatment on a five-point global assessment of study medication (Poor = 1 to Excellent = 5). All adverse events (AEs) were recorded. Of the 80 patients who entered the extension trials, 26 completed 52 weeks, 7 discontinued owing to loss of effectiveness, and 20 discontinued owing to AEs, most of which were unrelated to study drug. No significant increase in mean (standard deviation [SDD average pain intensity was observed from baseline (30.5 [19.6], 100-point scale) to final visit (35.9 [21.1], p = 0.37). The most common AEs were concomitant disease progression (28.8 percent, n=23), nausea (22.5 percent, n=18), dyspnea (16.3 percent, n=13), fatigue (16.3 percent, n=13), and edema of the lower limb (15 percent, n=12). In these patients with pain related to cancer, Oxymorphone ER was generally well tolerated and provided stable long-term pain control.
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considerations on the use of Oxymorphone in geriatric patients
Expert Opinion on Drug Safety, 2009Co-Authors: Joseph V. Pergolizzi, Robert B. Raffa, Errol M. GouldAbstract:Background: Pain among the elderly is pervasive, under-treated and can be properly managed by judiciously using analgesics in the armamentarium. For severe pain, opioids generally provide the most effective pain relief, but concerns about safety and tolerability have limited, often unnecessarily, their utilization in the geriatric population. Objective: It is common for geriatric patients to be taking more than one medicine. Oxymorphone might be particularly well suited for use in geriatric patients, in that its metabolism is mainly through non-CYPP450 pathways, thereby posing less risk of interaction with the many drugs that are metabolized by the CYPP450 system. However, Oxymorphone is not as familiar to clinicians as morphine or some other opioids. We review here the clinical studies on Oxymorphone to outline the key considerations for use of Oxymorphone in the geriatric population. Methods: Nine available clinical trials of Oxymorphone alone or comparing Oxymorphone with placebo or other active agents...
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Considerations on the use of Oxymorphone in geriatric patients.
Expert opinion on drug safety, 2009Co-Authors: Joseph V. Pergolizzi, Robert B. Raffa, Errol M. GouldAbstract:Pain among the elderly is pervasive, under-treated and can be properly managed by judiciously using analgesics in the armamentarium. For severe pain, opioids generally provide the most effective pain relief, but concerns about safety and tolerability have limited, often unnecessarily, their utilization in the geriatric population. It is common for geriatric patients to be taking more than one medicine. Oxymorphone might be particularly well suited for use in geriatric patients, in that its metabolism is mainly through non-CYPP450 pathways, thereby posing less risk of interaction with the many drugs that are metabolized by the CYPP450 system. However, Oxymorphone is not as familiar to clinicians as morphine or some other opioids. We review here the clinical studies on Oxymorphone to outline the key considerations for use of Oxymorphone in the geriatric population. Nine available clinical trials of Oxymorphone alone or comparing Oxymorphone with placebo or other active agents were analyzed with respect to the safety and tolerability findings. These studies included geriatric patients but were not designed to evaluate Oxymorphone exclusively in this population. Based on the results from nine published clinical studies, Oxymorphone is an effective opioid analgesic with a safety profile at least comparable to other opioid drugs. At low starting doses and individual titration, Oxymorphone should be considered for appropriate geriatric patients, particularly in whom there is concern about interaction with drugs that are metabolized by CYPP450 enzymes.
Irma H Benedek - One of the best experts on this subject based on the ideXlab platform.
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Original Research
2013Co-Authors: Bioequivalence Of Oxymorphone, Qinfang Xiang, Irma H Benedek, William D. Fiske, Endo Pharmaceuticals IncAbstract:extended release and crush-resistant Oxymorphone extended releas
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the effects of ethanol on the bioavailability of Oxymorphone extended release tablets and Oxymorphone crush resistant extended release tablets
The Journal of Pain, 2012Co-Authors: William Fiske, Janet Jobes, Qinfang Xiang, Souchan Chang, Irma H BenedekAbstract:Abstract Adverse events may occur with an extended-release (ER) opioid if tampering or coadministration with ethanol causes excessive exposure (dose dumping) to the opioid. The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of Oxymorphone ER and Oxymorphone crush-resistant formulation (CRF) were evaluated. In vitro dissolution rates were measured for Oxymorphone ER 40-mg and Oxymorphone CRF 40-mg tablets in aqueous solutions of 0 to 40% ethanol. In 2 in vivo, open-label, randomized, crossover studies, fasted healthy volunteers received single oral doses of Oxymorphone ER 40 mg or Oxymorphone CRF 40 mg with 240 mL of 0 to 40% ethanol. Naltrexone was used to minimize opioid effects. In the in vitro analyses, dissolution rates of Oxymorphone ER and CRF were unaffected in aqueous solutions of ≤40% ethanol. Coadministration of Oxymorphone ER or Oxymorphone CRF with ethanol 20 and 40% increased Oxymorphone peak plasma concentrations (C max ) by 14 to 80% and reduced time to C max . For both formulations, Oxymorphone area under the curve and terminal half-life were largely unaffected, but C max increased with ethanol dose. Neither Oxymorphone formulation exhibited dose dumping in terms of overall exposure when coingested with ethanol. Perspective Administering Oxymorphone ER or Oxymorphone CRF with 240 mL of ≤40% ethanol increased Oxymorphone C max without dose dumping in terms of area under the curve. These results provide reassurance about the integrity of Oxymorphone ER formulations with ethanol. Nonetheless, alcohol and opioids should never be combined because of the risk of respiratory depression.
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The Effects of Ethanol on the Bioavailability of Oxymorphone Extended-Release Tablets and Oxymorphone Crush-Resistant Extended-Release Tablets
The journal of pain : official journal of the American Pain Society, 2012Co-Authors: William D. Fiske, Janet Jobes, Qinfang Xiang, Souchan Chang, Irma H BenedekAbstract:Adverse events may occur with an extended-release (ER) opioid if tampering or coadministration with ethanol causes excessive exposure (dose dumping) to the opioid. The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of Oxymorphone ER and Oxymorphone crush-resistant formulation (CRF) were evaluated. In vitro dissolution rates were measured for Oxymorphone ER 40-mg and Oxymorphone CRF 40-mg tablets in aqueous solutions of 0 to 40% ethanol. In 2 in vivo, open-label, randomized, crossover studies, fasted healthy volunteers received single oral doses of Oxymorphone ER 40 mg or Oxymorphone CRF 40 mg with 240 mL of 0 to 40% ethanol. Naltrexone was used to minimize opioid effects. In the in vitro analyses, dissolution rates of Oxymorphone ER and CRF were unaffected in aqueous solutions of ≤40% ethanol. Coadministration of Oxymorphone ER or Oxymorphone CRF with ethanol 20 and 40% increased Oxymorphone peak plasma concentrations (C(max)) by 14 to 80% and reduced time to C(max). For both formulations, Oxymorphone area under the curve and terminal half-life were largely unaffected, but C(max) increased with ethanol dose. Neither Oxymorphone formulation exhibited dose dumping in terms of overall exposure when coingested with ethanol. Administering Oxymorphone ER or Oxymorphone CRF with 240 mL of ≤40% ethanol increased Oxymorphone C(max) without dose dumping in terms of area under the curve. These results provide reassurance about the integrity of Oxymorphone ER formulations with ethanol. Nonetheless, alcohol and opioids should never be combined because of the risk of respiratory depression. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
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Bioequivalence of Oxymorphone extended release and crush-resistant Oxymorphone extended release
Drug design development and therapy, 2011Co-Authors: Irma H Benedek, Janet Jobes, Qinfang Xiang, William D. FiskeAbstract:A formulation of crush-resistant extended-release opioids may deter abuse. The purpose of this study was to evaluate the bioequivalence of Oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of Oxymorphone extended-release (Oxy-CRF). In three open-label, randomized studies, healthy adults at a clinical research center received two single oral doses of Oxy-ER and two single doses of Oxy-CRF, each separated by a ≥7-day washout. Doses were administered under fasted conditions (study 1, 5 mg doses; study 2, 40 mg doses) or after a high-fat breakfast (study 3, 40 mg doses). Subjects administered 40 mg doses also received naltrexone. The primary endpoint was systemic Oxymorphone exposure; the bioequivalence criterion was met if the 90% confidence intervals of the geometric mean ratio (Oxy-CRF/Oxy-ER) for Oxymorphone area under the curve from time 0 to the last measured concentration (AUC(0-t)), AUC from time 0 to infinity (AUC(0-inf)), and maximum plasma concentration (C(max)) were within 0.8-1.25. Safety was assessed by monitoring adverse events. In studies 1, 2, and 3, the safety population comprised 30, 37, and 36 subjects and the pharmacokinetics population comprised 27, 30, and 29 subjects, respectively. Oxy-ER and Oxy-CRF produced similar mean ± standard deviation Oxymorphone AUC(0-t) (study 1, 5.05 ± 1.55 versus 5.29 ± 1.52 ng · h/mL; study 2, 31.51 ± 10.95 versus 31.23 ± 10.33 ng · h/mL; study 3, 50.16 ± 14.91 versus 49.01 ± 14.03 ng · h/mL) and C(max) (0.38 ± 0.11 versus 0.37 ± 0.12 ng/mL; 2.37 ± 1.20 versus 2.41 ± 0.94 ng/mL; 5.87 ± 1.99 versus 5.63 ± 2.26 ng/mL) under all conditions. The 90% confidence intervals for plasma Oxymorphone AUC(0-t), AUC(0-inf), and C(max) fulfilled the bioequivalence criterion. Adverse event rates were similar with Oxy-ER and Oxy-CRF (study 1, 25% versus 23%; study 2, 9% versus 16%; study 3, 20% each group). Oxy-CRF and Oxy-ER (5 mg and 40 mg) are bioequivalent under fasted and fed conditions, suggesting that Oxy-CRF will have clinical efficacy and safety equivalent to Oxy-ER.
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bioequivalence of Oxymorphone extended release and crush resistant Oxymorphone extended release
Drug Design Development and Therapy, 2011Co-Authors: Irma H Benedek, Janet Jobes, Qinfang Xiang, William D. FiskeAbstract:Background A formulation of crush-resistant extended-release opioids may deter abuse. The purpose of this study was to evaluate the bioequivalence of Oxymorphone extended-release (Oxy-ER) and a crush-resistant formulation of Oxymorphone extended-release (Oxy-CRF).
