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Opioids in non-cancer pain
Abstracts (865) A randomized, double-blind trial of low-dose oxymorphone immediate release (5 mg) for mild to moderate pain in ambulatory patients J. Gimbel, D. Walker; Arizona Research Center, Phoenix, AZ The aim was to compare the efficacy and safety of oxymorphone immediate release (IR) 5 mg with placebo for mild to moderate pain following knee arthroscopy. A randomized, double-blind study included men and women ⱖ18 years of age experiencing initial mild to moderate pain (30-70 mm on a 100-mm Visual Analog Scale) following outpatient knee arthroscopy. Various medications (i.e. COX-2 inhibitors, minor tranquilizers, muscle relaxants, and dextromethorphan-containing medications) were not permitted within 12-48 hours before dosing. Patients also were not permitted to use monoamine oxidase inhibitors within 2 weeks or tricyclic antidepressants, serotonin reuptake inhibitors or amphetamines within 4 weeks before dosing.. Following surgery, patients were randomized to either placebo or oxymorphone IR 5 mg. Patients took study medication q.h. as needed for up to 8 hours (8 dose maximum) and assessed pain at 30 minutes, 1 hour, and hourly up to 8 hours. Before each dose, patients recorded their worst pain, least pain, average pain, and pain at that time. The sum of pain intensity difference (VAS) over 0-8 hours was -4.2 (plus/minus 180.8) for placebo and 74.8 (plus/minus 127.4) for oxymorphone IR (P⫽0.007). The mean pain intensity differences (VAS) were statistically significant for 8 of 9 time points between 0 and 8 hours. In contrast to placebo patients, most patients receiving oxymorphone IR did not require rescue medication (P⫽0.0001), and 47% rated oxymorphone IR “very good” or “excellent” for pain relief compared with 25% receiving placebo. Most adverse events were similar in type and frequency between treatment groups; no patients taking oxymorphone IR discontinued because of adverse events. Low dose oxymorphone IR provided safe and effective treatment for mild to moderate acute pain in ambulatory patients. Partial support was provided by Endo Pharmaceuticals.
75 (867) Improved quality of life with Kadian姞 (morphine sulfate sustained-release capsules) in patients with chronic, non-malignant, moderate/severe pain: The KRONUS-MSP trial E. Ross, J. Sasaki, A. Weil, B. Nicholson; Brigham and Women‘s Hospital, Boston, MA Alleviating pain and sleep disturbances while minimizing adverse events are all important treatment goals in patients with chronic non-malignant pain; such “whole patient” management can improve quality of life (QoL). The KRONUS-MSP trial is the largest study to date to examine the use of a sustained-release opioid for chronic non-malignant pain, and includes measures of QoL. The aim was to assess the improvement in QoL in patients with chronic, non-malignant, moderate to severe pain with Kadian treatment. A community-based, prospective, randomized, open-label, blinded endpoint design was employed. Investigators randomized 1418 patients with chronic, non-malignant, moderate/severe pain and a baseline visual numeric scale (VNS) pain score ⱖ4 to a 4-week AM or PM QD regimen with Kadian. All patients had previous unsuccessful pain management. Dose adjustments were permitted; however, Q12h dosing was withheld until Week 2. Final evaluations occurred at Week 4. QoL was assessed using the SF36v2 Health Survey. Pain relief and sleep improvement were measured using a VNS (0-10 scale). Adverse events were collected and evaluated. A broad range of patients with diverse chronic non-malignant pain conditions displayed statistically significant improvements at Week 4 in the physical (12%) and mental (15.6%) composite scores of the SF36v2 (p⬍0.0001) as well as the VNS scores for pain relief (32%; p⬍0.0001) and sleep (29%; p⬍0.0001) compared to baseline. Kadian was well tolerated, with 70% (988/1418) of patients completing the study. Adverse events were reported by 40% (563/1418) of patients, with constipation (12%) and nausea (10%) being most frequent. Only 10% of patients discontinued due to adverse events. No differences in responses were seen between patients in the AM or PM dosing groups. Kadian therapy was efficacious, safe, well tolerated, and demonstrated improved QoL in a broad range of patients with chronic non-malignant pain.
(866) Long-term safety and effectiveness of oxymorphone ER in opioid-nanve patients with chronic pain
(868) Comparative clinical efficacy and abuse potential of oral long acting opioids in a chronic pain outpatient center
M. Hale, M. Drass; Gold Coast Research, L.L.C., Plantation, FL This 6-month, open-label study was conducted to assess the long-term safety and effectiveness of oxymorphone extended release (ER) in opioid-naı¨ve patients with moderate to severe chronic pain. This study included patients ⱖ 18 years of age with moderate to severe chronic pain (ⱖ 3 months’ duration) with no prior opioid use (within the past 3 months) who responded suboptimally to nonopioid analgesic treatment. Patients with an initial pain intensity score of ⱖ 40 on a 100-mm Visual Analog Scale and a pain rating of moderate or severe on a categorical scale received 2 days of therapy with oxymorphone ER 5 mg q12h. Patients were then titrated to a stable dose of oxymorphone ER that provided meaningful pain relief (⬍ 4 on a 0 to 10 scale for 3 out of 5 consecutive days); the titration period did not exceed 21 days. Following titration, patients could decrease or discontinue use of concomitant nonopioid analgesics while being maintained with the stabilized dose of oxymorphone ER therapy for up to 6 months. Rescue medication, oxymorphone immediate release 5 mg, was available only during the maintenance period. Efficacy and tolerability assessments included average daily pain intensity, average daily dose of oxymorphone ER, rescue medication, time to stabilization, adverse events, and patient and physician global assessments. Data from this 6-month study will be presented for approximately 100 patients. Conclusions will be based upon the trial results, and the implications for clinical management and research of chronic pain will be presented. The authors are grateful to Endo Pharmaceuticals Inc. and Penwest Pharmaceuticals Co. for providing partial support for this work.
M. Kaplan, A. Miliman, L. Kaplan, M. Collins; Rehabilitation Team West, Baltimore, MD Although opioids are oft used in pain management, misuse is a concern and may be due to immediate release (IR) opioid formulations or those that have an IR component and its attendant euphoria. We conducted a retrospective review of our experience switching between sustained release (SR) opioids over the last 5 years in our practice (⬃1,200 patients/ month). During an average week, we experienced 3 OxyContin-related incidents (15% incidence) such as “lost” scripts, unauthorized self dosing, or dosing more frequently than bid. Its variable IR component of 30-40% or more could be why patients are so resistant to transition to other SR opioids. Contrasting our OxyContin and Kadian experiences, we noted only one patient in over 5 years with such an incident. Kadian‘s low abuse potential is obvious as we never had a reported abuse case in over five years. While Avinza (⬃10% IR) is less problematic than OxyContin, only 2/30 patients who switched to Avinza continued on it after 3 months due to adverse effects (primarily nausea – 20/30 - that we believe was due to the IR component) or perceived lack of efficacy. When switching to Kadian qd, we noted an average of one patient every three weeks calling in between office visits, typically requesting to switch back to OxyContin or complained of inadequate analgesic duration (resolved by bid). Switching to Kadian provided substantial cost savings in personnel time. We believe that SR morphine without an IR component should be the first choice in chronic pain management and that IR breakthrough medications are better adjusted independently rather than prescribed as an SR/IR combination. Patients can be successfully transitioned from OxyContin to Kadian if one starts with about 60% IR oxycodone combined with Kadian 40% of the equivalent daily dose, reducing the IR portion over time while increasing the Kadian dose.
75 (867) Improved quality of life with Kadian姞 (morphine sulfate sustained-release capsules) in patients with chronic, non-malignant, moderate/severe pain: The KRONUS-MSP trial E. Ross, J. Sasaki, A. Weil, B. Nicholson; Brigham and Women‘s Hospital, Boston, MA Alleviating pain and sleep disturbances while minimizing adverse events are all important treatment goals in patients with chronic non-malignant pain; such “whole patient” management can improve quality of life (QoL). The KRONUS-MSP trial is the largest study to date to examine the use of a sustained-release opioid for chronic non-malignant pain, and includes measures of QoL. The aim was to assess the improvement in QoL in patients with chronic, non-malignant, moderate to severe pain with Kadian treatment. A community-based, prospective, randomized, open-label, blinded endpoint design was employed. Investigators randomized 1418 patients with chronic, non-malignant, moderate/severe pain and a baseline visual numeric scale (VNS) pain score ⱖ4 to a 4-week AM or PM QD regimen with Kadian. All patients had previous unsuccessful pain management. Dose adjustments were permitted; however, Q12h dosing was withheld until Week 2. Final evaluations occurred at Week 4. QoL was assessed using the SF36v2 Health Survey. Pain relief and sleep improvement were measured using a VNS (0-10 scale). Adverse events were collected and evaluated. A broad range of patients with diverse chronic non-malignant pain conditions displayed statistically significant improvements at Week 4 in the physical (12%) and mental (15.6%) composite scores of the SF36v2 (p⬍0.0001) as well as the VNS scores for pain relief (32%; p⬍0.0001) and sleep (29%; p⬍0.0001) compared to baseline. Kadian was well tolerated, with 70% (988/1418) of patients completing the study. Adverse events were reported by 40% (563/1418) of patients, with constipation (12%) and nausea (10%) being most frequent. Only 10% of patients discontinued due to adverse events. No differences in responses were seen between patients in the AM or PM dosing groups. Kadian therapy was efficacious, safe, well tolerated, and demonstrated improved QoL in a broad range of patients with chronic non-malignant pain.
(866) Long-term safety and effectiveness of oxymorphone ER in opioid-nanve patients with chronic pain
(868) Comparative clinical efficacy and abuse potential of oral long acting opioids in a chronic pain outpatient center
M. Hale, M. Drass; Gold Coast Research, L.L.C., Plantation, FL This 6-month, open-label study was conducted to assess the long-term safety and effectiveness of oxymorphone extended release (ER) in opioid-naı¨ve patients with moderate to severe chronic pain. This study included patients ⱖ 18 years of age with moderate to severe chronic pain (ⱖ 3 months’ duration) with no prior opioid use (within the past 3 months) who responded suboptimally to nonopioid analgesic treatment. Patients with an initial pain intensity score of ⱖ 40 on a 100-mm Visual Analog Scale and a pain rating of moderate or severe on a categorical scale received 2 days of therapy with oxymorphone ER 5 mg q12h. Patients were then titrated to a stable dose of oxymorphone ER that provided meaningful pain relief (⬍ 4 on a 0 to 10 scale for 3 out of 5 consecutive days); the titration period did not exceed 21 days. Following titration, patients could decrease or discontinue use of concomitant nonopioid analgesics while being maintained with the stabilized dose of oxymorphone ER therapy for up to 6 months. Rescue medication, oxymorphone immediate release 5 mg, was available only during the maintenance period. Efficacy and tolerability assessments included average daily pain intensity, average daily dose of oxymorphone ER, rescue medication, time to stabilization, adverse events, and patient and physician global assessments. Data from this 6-month study will be presented for approximately 100 patients. Conclusions will be based upon the trial results, and the implications for clinical management and research of chronic pain will be presented. The authors are grateful to Endo Pharmaceuticals Inc. and Penwest Pharmaceuticals Co. for providing partial support for this work.
M. Kaplan, A. Miliman, L. Kaplan, M. Collins; Rehabilitation Team West, Baltimore, MD Although opioids are oft used in pain management, misuse is a concern and may be due to immediate release (IR) opioid formulations or those that have an IR component and its attendant euphoria. We conducted a retrospective review of our experience switching between sustained release (SR) opioids over the last 5 years in our practice (⬃1,200 patients/ month). During an average week, we experienced 3 OxyContin-related incidents (15% incidence) such as “lost” scripts, unauthorized self dosing, or dosing more frequently than bid. Its variable IR component of 30-40% or more could be why patients are so resistant to transition to other SR opioids. Contrasting our OxyContin and Kadian experiences, we noted only one patient in over 5 years with such an incident. Kadian‘s low abuse potential is obvious as we never had a reported abuse case in over five years. While Avinza (⬃10% IR) is less problematic than OxyContin, only 2/30 patients who switched to Avinza continued on it after 3 months due to adverse effects (primarily nausea – 20/30 - that we believe was due to the IR component) or perceived lack of efficacy. When switching to Kadian qd, we noted an average of one patient every three weeks calling in between office visits, typically requesting to switch back to OxyContin or complained of inadequate analgesic duration (resolved by bid). Switching to Kadian provided substantial cost savings in personnel time. We believe that SR morphine without an IR component should be the first choice in chronic pain management and that IR breakthrough medications are better adjusted independently rather than prescribed as an SR/IR combination. Patients can be successfully transitioned from OxyContin to Kadian if one starts with about 60% IR oxycodone combined with Kadian 40% of the equivalent daily dose, reducing the IR portion over time while increasing the Kadian dose.