Oxycodone Hydrochloride Controlled-release Research Articles

Systemic Tremor Induced by Oxycodone Hydrochloride Controlled-Release Tablets in a Patient: A Case Report and Mechanism Exploration

Systemic Tremor Induced by Oxycodone Hydrochloride Controlled-Release Tablets in a Patient: A Case Report and Mechanism Exploration

Safety and Efficacy of Once-Daily Hydromorphone Extended-Release Versus Twice-Daily Oxycodone Hydrochloride Controlled-Release in Chinese Patients With Cancer Pain: A Phase 3, Randomized, Double-Blind, Multicenter Study

Noninferiority of the efficacy of once-daily hydromorphone hydrochloride extended-release (hydromorphone ER) compared with twice-daily oxycodone hydrochloride controlled-release (oxycodone CR) was investigated in this randomized, double-blind study in Chinese patients with moderate to severe cancer pain requiring strong oral opioid analgesics. Randomization (1:1) to hydromorphone ER (8–32 mg) or oxycodone CR (10–40 mg) was followed by dose titration (up to 8 days) and dose maintenance (28 days, weekly visits). Primary endpoint was change from baseline to end of study in “worst pain in the past 24 hours” of Brief Pain Inventory (Short Form) score on last observation carried forward (per protocol set). A total of 137 of 260 randomized patients completed maintenance phase (hydromorphone ER: n = 70; oxycodone CR: n = 67); per protocol set: 81 patients. Mean age was 53.1 years (range: 18–70 years; males: 65.3%); most common Eastern Cooperative Oncology Group performance status = 2. Least square mean difference between 2 treatment groups for primary endpoint using analysis of covariance (baseline score, covariate) was −.1 (95% confidence interval: −1.3, 1.1), with upper bound of 95% confidence interval <1.5 (predefined noninferiority margin). Most common reason for deaths was disease progression (hydromorphone ER: 6.3%; oxycodone CR: 12.7%). Treatment-emergent adverse events were comparable between treatment groups. Hydromorphone ER was noninferior to oxycodone CR in alleviating cancer pain and was well tolerated. PerspectiveThis article demonstrates clinical noninferiority of the efficacy of once-daily hydromorphone ER compared with twice-daily oxycodone CR in alleviating cancer pain in Chinese patients, with comparable safety profiles between the 2 treatment groups. Thus, a treatment option with the potential for a reduced dosing frequency exists for health care providers and patients.

Changes in Prevalence of Prescription Opioid Abuse after Introduction of an Abuse-Deterrent Opioid Formulation

The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). Observational, cross-sectional study Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.

Abuse Rates and Routes of Administration of Reformulated Extended-Release Oxycodone: Initial Findings From a Sentinel Surveillance Sample of Individuals Assessed for Substance Abuse Treatment

Oxycodone hydrochloride controlled-release, also known as extended-release oxycodone (ER oxycodone), was reformulated with physicochemical barriers to crushing and dissolving intended to reduce abuse through nonoral routes of administration (ROAs) that require tampering (eg, injecting and snorting). Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010, and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for prevalence and prescription-adjusted prevalence rates of past-30-day abuse via any route, as well as abuse through oral, nonoral, and specific ROAs for ER oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF introduction. Significant reductions occurred for 8 outcome measures of ORF versus OC historically. Abuse of ORF was 41% lower (95% CI: −44 to −37) than historical abuse for OC, with oral abuse 17% lower (95% CI: −23 to −10) and nonoral abuse 66% lower (95% CI: −69 to −63). Significant reductions were not observed for comparators. Observations were consistent with the goals of a tamper resistant formulation for an opioid. Further research is needed to determine the persistence and generalizability of these findings. PerspectiveThis article presents preliminary findings indicating that 8 outcome measures of abuse of a reformulated ER oxycodone were lower than that for original ER oxycodone historically, particularly through nonoral ROAs that require tampering (ie, injection, snorting, smoking), in a sentinel sample of individuals assessed for substance use problems for treatment planning.

Oxycodone hydrochloride controlled-release tablets (OxyContin®): post-marketing surveillance (PMS) study for relieving moderate to severe non-cancer pain

Objective To evaluate the efficacy and safety of oxycodone hydrochloride controlled-release (CR) tablets (Oxycontin®, Mundipharma International Limited, Cambridge, UK), 5 mg, 10 mg, 20 mg, and 40 mg in relieving moderate to severe non-cancer pain. Method Two multi-center, open-label, prospective, self-controlled clinical trial, used identical protocols. All the subjects were patients with moderate to severe non-cancer pain. The clinical data were collected in the natural course of clinical treatment. Results Treatments with oxycodone CR tablets was associated with fast onset on pain relief; 85.2% of patients in study 1 and 91.8% of patients in study 2 achieved pain relief within 1 hour of drug administration. Clinical efficacy Both studies demonstrated that oxycodone CR tablets showed good clinical efficacy for relieving both moderate and severe non-cancer pain. Patients experienced sustained pain relief from the first week of treatment. Patients in both study 1 and study 2 experienced a dramatic pain score reduction (as assessed by VAS) after the first week of treatment. Safety profile During oxycodone CR treatment, use of concomitant medications decreased significantly. A few patients developed ADRs in the first week, which decreased significantly as the treatment continued. Constipation was the most common ADR in the first week, which decreased to 10% of patients from the second week of treatment. Conclusion Oxycodone CR tablets demonstrated fast onset of pain control and superior efficacy for relieving both moderate and severe non-cancer pain, as well as significant reductions in the number of concomitant medications, demonstrating a good safety profile.

(765): Long-term improvement in physical function observed in the ACTION Trial: A randomized, multi-center study of once daily AVINZA® (morphine sulfate extended-release capsules) versus twice daily OxyContin® (oxycodone hydrochloride controlled-release) for modera

The ACTION trial compared once daily AVINZA to twice daily OxyContin in subjects 30-70 years old with chronic moderate to severe low back pain. After opioid dose titration, subjects entered an 8-week evaluation phase followed by an optional 4-month extension phase. In addition to assessment of pain scores, sleep, opioid dose, and ibuprofen use for breakthrough pain, subjects completed the SF-12® quality of life questionnaire and the Work Limitations Questionnaire® (WLQ), at baseline, at the end of the dose-titration, and then monthly x6 months.

Efficacy and Tolerability of Oxycodone Hydrochloride Controlled-Release Tablets in Moderate to Severe Cancer Pain

Oxycodone is a semisynthetic opioid analgesic drug classed as a strong opioid. The controlled-release oxycodone tablet formulation (OCRT) was approved in China in 2004 for management of moderate to severe cancer pain. Few data about the efficacy of OCRT and clinical outcomes in Chinese patients taking this drug are available. The purpose of this study was to evaluate the efficacy and tolerability of this drug for relief of moderate to severe cancer pain in Chinese patients. This was a prospective, open-label, multicentre clinical trial carried out in ten hospitals in Zhejiang Province, China. Patients with cancer pain with a score > or =4 (numerical rating scale) were enrolled. They received oral OCRT at an initial dosage of 5mg every 12 hours for patients scoring 4-6 and 10mg every 12 hours for patients scoring > or =7. Doses were then titrated on an individual basis. Onset of analgesic action, pain score and quality-of-life (QOL) scores - including items measuring family understanding and support, sleep, mental state, appetite, fatigue, and activities of daily life - were evaluated. Adverse effects were also documented. 216 patients (126 males and 90 females) aged 22-84 years were enrolled. The total mean OCRT dosage was 445.2 +/- 361.6mg (range 130-2320mg). The daily dosages of the vast majority of cases (89%) were between 10mg and 30mg. Onset of analgesic action occurred within 1 hour in 198 cases (91.7%) following administration of OCRT. 82.4% of cases were titrated to a steady dosage level within 2 days following administration of the first dose of medication. Pain score decreased significantly (p < 0.01) from 7.1 +/- 1.2 at baseline to 2.3 +/- 1.2 one week after starting medication and 1.8 +/- 0.9 four weeks after starting medication. Scores on all six QOL items increased significantly (p < 0.01) compared with baseline but showed varying rates of improvement. Adverse events included constipation, nausea, vomiting, drowsiness and dysuria. These were noted most frequently in the first week (25.5% of patients) and lessened over time. No severe adverse events were noted. We conclude that OCRT is well tolerated and effective in controlling moderate to severe cancer pain in Chinese patients.

(813): Oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice daily OxyContin (oxycodone hydrochloride controlled-release): A randomized, multicenter study for the treatment of chronic moderate to severe low back pain

We evaluated and compared two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in patients with chronic moderate-to-severe low back pain. This was an open-label, randomized, parallel-group multicenter study open to enrollment of SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe (pain score ’4 on a 0-10 BPI scale) low back pain. A total of 392 subjects were enrolled and underwent opioid dose titration for a period of 3 to 6 weeks. Opioid dose stabilization (pain score< 4 for 3 consecutive days with≤ 2 doses of ibuprofen pain rescue medication per day) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered the 8-week evaluation phase of the study. AVINZA achieved pain control that was significantly better than OxyContin, as demonstrated by a greater decrease from baseline in pain scores evaluated 6, 9, and 12 hours after the morning dose of both opioids (p≤0.02). Subjective sleep parameters assessed by the PSQI were significantly better in the AVINZA group for the entire Evaluation period from Week 1 to 8 (p<0.04). The number of ibuprofen pain rescue medication doses adjusted for the number of patient-days was significantly lower in the AVINZA group (p<0.01). Pain control was achieved with a significantly lower daily opioid dose expressed in morphine-equivalents in the AVINZA group (median of 58 mg and 85 mg, respectively p=0.017). The incidence and severity of elicited opioid side effects was similar in the two treatment groups. This randomized trial showed that AVINZA was significantly better than OxyContin for around-the-clock pain relief and improved sleep, with the added advantage of once-a-day dosing, a lower median morphine-equivalent daily dose, fewer ibuprofen doses for breakthrough pain, and a comparable safety profile. Supported by Ligand Pharmaceuticals Inc, and Organon Pharmaceuticals USA Inc.

(827): Oral once-a-day AVINZA (morphine sulfate extended-release capsules) vs. twice daily OxyContin (oxycodone hydrochloride controlled-release) for the treatment of chronic moderate-to-severe low back pain; final (part I and part II) study results

This open-label, randomized, parallel-group multicenter study evaluated the efficacy and safety of two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe low back pain. During Part I of the study 392 subjects enrolled and underwent opioid dose titration (3 to 6 weeks). Opioid dose stabilization (pain score ≤4 for 3 consecutive days with ≤2 doses per day of ibuprofen for breakthrough pain) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered an 8-week evaluation period. Following completion of Part I of the study, 174 subjects (95 AVINZA and 79 OxyContin) entered a 4-month extension phase (Part II). During Part I, AVINZA achieved significantly better pain scores (p≤ 0.02) and sleep parameters (p< 0.04) than OxyContin. These improvements were achieved with a significantly lower total daily opioid dose expressed in morphine-equivalents (median of 58mg for AVINZA and 85mg for OxyContin, p=0.017). Ibuprofen doses adjusted for the number of patient-days were significantly lower in the AVINZA group (p<0.01). These clinical benefits were maintained or further improved during Part II. At the end of Part I, the mean NRS pain scores were 3.5 for AVINZA and 3.8 for OxyContin, and further decreased to 3.1 and 3.5, respectively, at Month 4, the end of Part II (p= 0.01 favoring AVINZA). Improvements in the quality of sleep were also maintained. These results were achieved with a significantly lower daily opioid dose in the AVINZA group (86mg) compared to OxyContin (119mg morphine-equivalents) with p =0.0029. The incidence and severity of elicited opioid side effects was similar in the two treatment groups during both study phases. Final results for both parts will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc. This open-label, randomized, parallel-group multicenter study evaluated the efficacy and safety of two oral SROs (once-a-day AVINZA® and twice-a-day OxyContin®) in SRO-naive subjects, age 30-70, with chronic (≥ 6 months) moderate-to-severe low back pain. During Part I of the study 392 subjects enrolled and underwent opioid dose titration (3 to 6 weeks). Opioid dose stabilization (pain score ≤4 for 3 consecutive days with ≤2 doses per day of ibuprofen for breakthrough pain) was achieved in 266 subjects (132 randomized to AVINZA and 134 to OxyContin) who then entered an 8-week evaluation period. Following completion of Part I of the study, 174 subjects (95 AVINZA and 79 OxyContin) entered a 4-month extension phase (Part II). During Part I, AVINZA achieved significantly better pain scores (p≤ 0.02) and sleep parameters (p< 0.04) than OxyContin. These improvements were achieved with a significantly lower total daily opioid dose expressed in morphine-equivalents (median of 58mg for AVINZA and 85mg for OxyContin, p=0.017). Ibuprofen doses adjusted for the number of patient-days were significantly lower in the AVINZA group (p<0.01). These clinical benefits were maintained or further improved during Part II. At the end of Part I, the mean NRS pain scores were 3.5 for AVINZA and 3.8 for OxyContin, and further decreased to 3.1 and 3.5, respectively, at Month 4, the end of Part II (p= 0.01 favoring AVINZA). Improvements in the quality of sleep were also maintained. These results were achieved with a significantly lower daily opioid dose in the AVINZA group (86mg) compared to OxyContin (119mg morphine-equivalents) with p =0.0029. The incidence and severity of elicited opioid side effects was similar in the two treatment groups during both study phases. Final results for both parts will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc.

Randomized, multi-center study of oral once-a-day AVINZA® (morphine sulfate extended-release capsules) vs. twice daily OxyContin® (oxycodone hydrochloride controlled-release) for the treatment of chronic moderate to severe low back pain

This 8-week randomized, parallel-group, multi-center study will evaluate the efficacy of oral once daily AVINZA vs. twice daily OxyContin in patients 30–70 years old requiring opioid therapy for chronic moderate to severe low back pain. Inclusion criteria include a diagnosis of chronic pain; prior sub-optimal analgesic response to treatment with other medications including NSAIDS, acetaminophen and/or prior intermittent immediate release opioid analgesics; currently not taking sustained release opioids (SROs) for pain; and demonstration of a baseline pain intensity score of >4 on an 11 point numerical scale (0= no pain; 10= pain as bad as you can imagine).

Risk of Constipation in Patients Prescribed Fentanyl Transdermal System or Oxycodone Hydrochloride Controlled-Release in a California Medicaid Population

To compare the risk of developing constipation between patients prescribed fentanyl transdermal system or oxycodone hydrochloride (HCl) controlled-release. California Medicaid (Medi-Cal) claims data. Medicaid beneficiaries in California. Chronic pain patients who received a prescription for transdermal fentanyl or oxycodone controlled-release between October 1, 1997, and February 28, 2000, for at least three consecutive months. Constipation was defined using the International Classification of Diseases, Ninth Revision, Clinical Modification code (ICD-9-CM 564.0). The association between long-acting opioid use and constipation was determined by multivariate logistic regression after controlling for drug strength, short-acting opioid usage, and comorbidities. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were reported. A total of 2,095 patients were included in the regression analysis (transdermal fentanyl = 877; oxycodone controlled-release = 1,218). Seventy-five patients received a constipation diagnosis (transdermal fentanyl = 28; oxycodone controlled-release = 47). Approximately 40% of patients were at least 65 years of age. Overall, oxycodone controlled-release patients had a significantly greater risk of developing constipation compared with transdermal fentanyl patients (transdermal fentanyl: n = 877; oxycodone controlled-release: n=1,218; OR = 2.55; 95% CI = 1.33-4.89; P = 0.005). Among patients who were 65 years or older, oxycodone controlled-release patients were 7.33 times more likely to be constipated than transdermal fentanyl patients (transdermal fentanyl: n = 518; oxycodone controlled-release: n = 317; OR = 7.33; 95% CI = 1.98-27.13; P = 0.003). These findings suggest that patients prescribed transdermal fentanyl may have a significantly lower risk of developing constipation compared with oxycodone controlled-release, particularly in the elderly.

Cost and Utilization Patterns of Fentanyl Transdermal System and Oxycodone Hydrochloride Controlled-Release in a California Medicaid Population

CONTEXT: Although opioid analgesics are becoming an accepted part of pain management, detailed information about pharmacy claims for these medications is limited. OBJECTIVE: The purpose of this stu...