Controlled-release Oxycodone Research Articles

Reduced Cognitive and Psychomotor Impairment with Extended-Release Oxymorphone Versus Controlled-Release Oxycodone

Background: Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. Objective: To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Study design: Randomized, double-blind, 5-way crossover Setting: Single inpatient research unit Methods: Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory PentobarbitalChlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OCCR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. Results: Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired; 81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER. Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30 mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness). Limitations: Participants were young, healthy volunteer nondependent recreational drug users, and only single doses were evaluated. The effects of tampering or higher doses were not assessed. Conclusions: Single oral intact low and high doses of OM-ER produced less cognitive and psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study. ClinicalTrials.gov registration NCT00955110 Key words: opioid, cognitive effects, psychomotor effects, sedation, dysphoria, oxymorphone, oxycodone, long-acting opioids

Oral Hydromorphone Extended-Release

To review the chemistry, pharmacodynamics, pharmacokinetics, efficacy, tolerability, dosing, and role of the Osmotic-controlled Release Oral delivery System (OROS) hydromorphone extended-release (ER) tablets. A MEDLINE/PUBMED search (1986-August 2010) was conducted to identify studies in the English language, with additional references being obtained from their bibliographies. All studies of hydromorphone ER were reviewed. This is the second long-acting hydromorphone formulation to receive approval by the Food and Drug Administration (a twice-daily formulation was approved in September 2004, but was subsequently withdrawn in July 2005). Hydromorphone is a semi-synthetic mu-opioid receptor agonist structurally similar to morphine, hydrocodone, and oxymorphone. OROS ER technology allows once-daily dosing. Clinical trials have focused on the convertibility of (an) other opioid(s) to hydromorphone ER in chronic malignant and nonmalignant pain. This product displays the expected opioid side effects, being comparable to oxycodone controlled-release. Coadministration with ethanol does not produce the degree of "dose-dumping" seen with the former hydromorphone twice-daily product or oxymorphone ER. Hydromorphone ER is indicated for the management of moderate-to-severe pain in opioidtolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time. Dosage adjustment is recommended in patients with moderate hepatic impairment (Child-Pugh class B) and moderate renal impairment (creatinine clearance of 30-60 mL/min). Hydromorphone ER is the newest oral opioid to enter a crowded marketplace now totaling 15 different Schedule 2 opioids (including tapentadol), and tramadol, available in oral, parenteral, rectal, transdermal, transmucosal, and intranasal formulations. It does not appear to have any unique assets or liabilities and should be considered as one of many oral opioids available for the management of persistent pain of moderate-to-severe intensity.

A retrospective chart review of opioid-induced nausea and somnolence on commencement for cancer pain treatment

Morphine, oxycodone, and fentanyl are major opioids available as controlled-release morphine (CRM), controlled-release oxycodone (CRO), and transdermal fentanyl (TDF), respectively, in Japan. The authors conducted a retrospective chart review to examine (1) nausea and somnolence on commencement of CRM, CRO, and TDF for cancer pain treatment, (2) the antiemetic effectiveness of prochlorperazine to prevent opioid-induced nausea, and (3) the side effect of prochlorperazine on somnolence in patients with cancer pain. Four hundred thirteen patients with cancer were prescribed with CRM (N = 66), CRO (N = 196), and TDF (N = 151). The incidence of nausea on commencement of the TDF group (6.8 percent) was significantly lower than that of both the CRM group (22.6 percent) and the CRO group (35.4 percent; p < 0.001). There was no significant difference in the incidence of nausea on commencement of all groups combined with prochlorperazine at dosage of 15 mg/d. The incidence of somnolence on commencement of the TDF group (9.0 percent) was significantly lower than that of both the CRM group (31.3 percent) and the CRO group (41.5 percent; p < 0.001). The incidence of somnolence on commencement of the CRO group combined with prochlorperazine was significantly higher than that of the CRO combined without prochlorperazine (p < 0.05). In conclusion, the incidence of nausea and somnolence on commencement of TDF are significantly lower than that of both CRM and CRO for cancer pain treatment. Prochlorperazine at a dosage of 15 mg/d may not be effective in preventing opioid-induced nausea and may cause somnolence in patients with cancer pain.

The Use of High Doses of Oxycodone in an Acute Palliative Care Unit

A retrospective study of patients who were prescribed controlled-release oxycodone (CRO) in a period of 3 years (2006-2008) was performed. A total of 212 patients were prescribed at discharge CRO for background analgesia; 129, 43, and 40 patients were prescribed doses of oxycodone of less than 120 mg/day (group L), 120 to 240 mg/day (group M), and more than 240 mg/day (group L), respectively. No differences in gender, primary diagnosis, and pain mechanisms were found, but doses were significantly lower in older patients (P < .0005). At discharge, adverse effects were mild and only a minority of patients were switched to other opioids. This study demonstrated that CRO administered in larger doses was safe and effective, showing versatility and flexibility similar to morphine.

Opioid Formulations Designed to Resist/Deter Abuse

Physicians who prescribe opioid analgesics for patients with moderate to severe chronic pain face a balancing act in the wake of the current publicity regarding abuse (nonmedical use) of prescription pain killers. There is a spectrum of opioid abuse ranging from those who misuse the drug by not following doctor's orders to those who take the drugs to achieve a high or divert the drugs to the street market for profit. Formulations of opioid analgesics designed to resist or deter abuse have been proposed, and are now either on the market or in the pipeline. These are innovative formulations that make the drug less convenient or less desirable to abusers. This article examines three such new products along with clinical studies that report on their safety and effectiveness. These drugs include extended-release morphine with sequestered naloxone (Embeda), controlled-release oxycodone in a high-viscosity hard gelatin capsule (Remoxy) and an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent (Acurox with niacin tablets). Extended-release morphine with sequestered naltrexone offers a pharmacological barrier in that pellets of morphine surround an internal core of naltrexone (ratio 100 : 4 of morphine : naltrexone), which is released if the tablet is compromised by chewing or crushing. The hard gelatin capsule of controlled-release oxycodone was designed to resist tampering and the drug cannot be extracted with a needle. The immediate-release oxycodone formulation with subtherapeutic niacin uses a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The subtherapeutic niacin is intended to induce flushing and other unpleasant effects if the drug is taken in an excessive quantity. While these drugs hold individual promise, it remains undetermined if they can truly prevent abuse. Drug-seeking individuals are extremely resourceful and show little loyalty to a particular drug when other drugs are available. It is possible that abuse-deterring formulations may divert such individuals to find other drugs that are easier to compromise. Nevertheless, these formulations are important innovations and warrant further study to assess their appropriate role as analgesics.

Efficacy and Safety of Tapentadol Extended Release Compared with Oxycodone Controlled Release for the Management of Moderate to Severe Chronic Pain Related to Osteoarthritis of the Knee

Tapentadol is a novel, centrally acting analgesic with mu-opioid receptor agonist and norepinephrine reuptake inhibitor activity. to evaluate the efficacy and safety of Tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain. this was a randomized, double-blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received Tapentadol ER, oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive Tapentadol ER 100-250 mg twice daily, oxycodone HCl CR 20-50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation. efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], -0.7 [-1.04, -0.33]), and throughout the maintenance period (-0.7 [-1.00, -0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], -0.3 [-0.67, -0.00]) but not at week 12 (-0.3 [-0.68, 0.02]). A significantly higher percentage of patients achieved > or =50% improvement in pain intensity in the Tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved > or =50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, Tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342). treatment with Tapentadol ER 100-250 mg twice daily or oxycodone HCl CR 20-50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with Tapentadol ER than with oxycodone CR.

Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study

Objective: To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain.Research design: Patients (N = 981) were randomized 1:1:1 to receive tapentadol ER 100 – 250 mg b.i.d., oxycodone HCl controlled release (CR) 20 – 50 mg b.i.d., or placebo over 15 weeks (3-week titration period, 12-week maintenance period).Main outcome measures: Efficacy was assessed as change from baseline in average pain intensity (11-point NRS) at week 12 of the maintenance period and throughout the maintenance period; last observation carried forward was used to impute missing pain scores. Adverse events (AEs) were monitored throughout the study.Results: Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 (least squares mean difference vs placebo [95% confidence interval], −0.8 [−1.22, −0.47]; p < 0.001) and throughout the maintenance period (−0.7 [−1.06,−0.35]; p < 0.001). Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 (−0.9 [−1.24,−0.49]; p < 0.001) and throughout the maintenance period (−0.8 [−1.16,−0.46]; p < 0.001). Tapentadol ER was associated with a lower incidence of treatment-emergent AEs (TEAEs) than oxycodone CR. Gastrointestinal TEAEs, including constipation, nausea, and vomiting, were among the most commonly reported TEAEs (placebo, 26.3%; tapentadol ER, 43.7%; oxycodone CR, 61.9%). The odds of experiencing constipation or the composite of nausea and/or vomiting were significantly lower with tapentadol ER than with oxycodone CR (both p < 0.001).Conclusions: Tapentadol ER (100 – 250 mg b.i.d.) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR (20 – 50 mg b.i.d.).

Cancer pain management with hydromorphone OROS in Korean cancer patients: Evaluation of its clinical usefulness in reduction of breakthrough pain medication frequency: Multicenter, prospective, open-label study.

e19566 Background: A majority of patients with cancer experience cancer pain of higher than moderate severity during the progression of cancer. Of these, 2/3 of patients with cancer have been reported to be inflicted with breakthrough pain. Methods: The primary objective is to evaluate the clinical usefulness of hydromorphone OROS in reduction of breakthrough pain medication frequency in Korean patients. Subjects include patients who are given strong oral narcotic analgesics for the treatment of cancer pain. This study enrolled only patients who took immediate-release analgesics more than twice a day on average for the treatment of breakthrough pain during a 3-day period prior to Visit 2. When patients selected, patients were switched to test drug using a 2.5: 1 conversion ratio of controlled release oxycodone equivalent to hydromorphone hydrochloride, with no washout or overlap of previous opioid therapy and study medication. Results: Total 117 patients received the investigational drug and only 98 patients completed the last fourth assessment. The frequency of the use of immediate- release analgesics for the management of breakthrough pain was decreased from 2.93 times to 2.00 times (p<0.000). The incidence of breakthrough pain was also decreased from 3.67 times to 2.44 times (p<0.0001). K-BPI score was also decreased from 3.6 to 3.2. In 61.2% of patients had a satisfaction with the pain treatment. In regard to the preference to test drug in 83.7% of patients who completed the treatment, 82.95% of patients preferred test drug because ‘the cancer pain could be controlled with a one-time treatment'. 25.5% of patients showed improvement of CGI-I. In EORTC QLQ-C30 analysis, only pain and diarrhea among the symptom scales improved. In 91.2% of patients who used analgesics, the side effects occurred in such an order as constipation, drowsiness and dizziness. But there were no cases of uncontrolled specific side effects. Conclusions: A 24-hr sustained-release type of hydromorphone OROS tablet significantly diminished the use of immediate-release analgesics and the incidence of breakthrough pain. No significant financial relationships to disclose.

Safety and tolerability of tapentadol extended release (ER) versus oxycodone controlled release (CR) in elderly patients with chronic low back or osteoarthritis pain

In a phase 3, randomized, open-label, 1-year safety study in adults with moderate-to-severe chronic low back or osteoarthritis pain, tapentadol ER (100-250mg bid) provided similar pain relief to oxycodone HCl CR (20-50mg bid), with improved gastrointestinal tolerability (ClinicalTrials.gov Identifier:NCT00361504). This post-hoc analysis evaluated incidences of and study discontinuations due to overall and gastrointestinal treatment-emergent adverse events (TEAEs) among patients ≥65 years of age. Times to onset of and discontinuations due to constipation, nausea, or vomiting were estimated using Kaplan-Meier plots (treatment differences compared using the log-rank test); the percentage of treatment days with these TEAEs was calculated (treatment differences compared using the Wilcoxon test). Of 1,117 patients analyzed for safety, 312 were ≥65 years (tapentadol ER, n=245; oxycodone CR, n=67). Among patients ≥65 years in the tapentadol ER and oxycodone CR groups, respectively, 87.8% and 94.0% of patients reported ≥1 TEAE and 57.6% and 76.1% of patients reported gastrointestinal TEAEs (most were mild or moderate). Patients ≥65 years who received tapentadol ER versus oxycodone CR experienced significantly lower percentages of treatment days with nausea (5.39% vs 14.0%), vomiting (2.4% vs 7.2%), or constipation (14.9% vs 31.6%); all nominal P≤0.0021. Times to first onset of these TEAEs were significantly longer with tapentadol ER versus oxycodone CR (all nominal P≤0.0002 [log-rank test]). In the tapentadol ER and oxycodone CR groups, respectively, any TEAE led to study discontinuation in 33.1% and 49.3% and gastrointestinal TEAEs led to study discontinuation in 14.3% and 31.3% of patients ≥65 years. Times to withdrawal due to nausea, vomiting, or constipation were significantly longer with tapentadol ER versus oxycodone CR (all nominal P≤0.0099). Tapentadol ER was associated with better gastrointestinal tolerability and a lower rate of study discontinuations due to TEAEs than oxycodone CR in patients ≥65 with moderate-to-severe chronic pain. (OMJSA and Grünenthal GmbH supported this study.)

Oral intact extended-release oxymorphone is associated with less cognitive and psychomotor impairment than equianalgesic doses of oral intact controlled-release oxycodone in healthy nondependent recreational opioid users

Cognitive sequelae of opioid treatments for chronic pain are an important clinical concern. To assess cognitive effects of oxymorphone extended release (ER; 15 and 30 mg) and oxycodone controlled release (CR; 30 and 60 mg) in healthy nondependent recreational opioid users, an exploratory, randomized, double-blind, placebo-controlled 5-way crossover study was conducted. Subjects received single oral intact doses of opioids and placebo with a ≥7-day washout period between treatments. Sedation and cognitive effects were assessed using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) scale, Alertness/Drowsiness Visual Analog Scale (A/D-VAS), and Divided Attention (DA) test.

Oral intact extended-release oxymorphone is associated with less liking and lower positive subjective effects than equianalgesic doses of oral intact controlled-release oxycodone in healthy nondependent recreational opioid users

When prescribing opioids for chronic pain, abuse potential is a prominent consideration. Euphoria and positive subjective effects such as Drug Liking or Good Effects might contribute to potential for abuse. This exploratory, randomized, double-blind, placebo-controlled 5-way crossover study compared the positive subjective effects of equianalgesic doses of oxymorphone extended release (ER; 15 and 30 mg) and oxycodone controlled release (CR; 30 and 60 mg) in healthy nondependent recreational opioid users.

Controlled-release oxycodone alone or combined with gabapentin for management of malignant neuropathic pain

Objective: To evaluate the analgesic efficacy of controlled-release (CR) oxycodone and gabapentin in malignant neuropathic pain (NP). Methods: Patients with malignant NP were enrolled and baseline pain intensity (PI) was recorded. They initially took one week CR oxycodone and were allocated to two different groups at day 8 by reevaluated PI. Patients with mild pain went to CR oxycodone mono-therapy group (OO group) and took another two weeks CR oxycodone. Others went to (CR oxycodone combined gabapentin group (OG group) and received additional gabapentin. Daily doses and side effects were recorded. Results: Fifty-eight (92.06%) of the 63 enrolled patients completed the initial week’s therapy. Twenty-two (37.93%) went to OO group and PI significantly reduced at day 15 (2.00 vs. 2.62, P=0.004), but not improved at day 22 (1.90 vs. 2.00, P=0.54). Thirty-six (62.07%) patients went to OG group and PI was significantly reduced at day 15 (4.47 vs. 2.94, P Conclusion: Malignant NP may be well controlled by oxycodone mono-therapy. Early combination with gabapentin is sensible when pain is not satisfactory relieved by oxycodone alone. The side effects of them are manageable.

Clinical Equivalence of Controlled-Release Oxycodone 20 mg and Controlled-Release Tramadol 200 mg after Surgery for Breast Cancer

Aims: To assess clinical equivalence of 20 mg controlled-release oxycodone (Oxygesic®; Mundipharma, Limburg, Germany) and 200 mg controlled-release tramadol (Tramal long®; Grünenthal, Aachen, Germany) on a 12-hour dosing schedule in a randomized, double-blinded study of 54 ASA I–III physical status (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer. Methods: General anesthesia using remifentanil and propofol was performed for surgery. Patients were randomly allocated to 2 groups, receiving either 20 mg controlled-release oxycodone (Oxy group) or 200 mg controlled-release tramadol (Trama group) with the premedication (7.5 mg midazolam) and again 12 hours later. All patients had access to rescue medication (i.v. paracetamol). The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 24 hours after operation. The equivalence margin was determined as ±10 on the visual analogue scale. Results: Fifty-four patients were enrolled. Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 24 hours after operation was found to be within the predefined equivalence margin [–4.5 to +1.7], and the CI values for pain scores on coughing [–6.2 to +1.7] were similar. Cumulative paracetamol given over the 24-hour observation period did not differ significantly between the Oxy group (1.32 ±1.9 g) and the Trama group (1.61 ± 1.1 g; p = 0.32). There were no significant differences between the treatment groups regarding adverse events such as nausea (p = 0.13), vomiting (p = 0.24) and itching (p = 0.77). Also, no differences were found concerning patient satisfaction scores (p = 0.8) or patients’ general perception of postoperative pain management (p = 0.71). Conclusion: 20 mg controlled-release oxycodone is clinically equivalent to 200 mg controlled-release tramadol for postoperative analgesia after surgery for breast cancer.

Oxycodone: new ‘old’ drug

Since the introduction of oral immediate release and controlled-release oxycodone preparations to the market in the 1990s, the clinical use and scientific interest in oxycodone has increased greatly. Recent studies have shown that the pharmacokinetics of oxycodone are dependent on age of the patient and therefore individual titration of the dose is necessary, especially in the elderly. Oxycodone has good oral bioavailability and it produces more predictable plasma concentrations than morphine, which has a poor and more variable bioavailability. Oxycodone has clinically significant drug interactions with drugs affecting cytochrome P450 3A enzymes. Clinical studies have demonstrated that oxycodone is a useful opioid analgesic in acute postoperative pain, cancer pain, visceral pain and chronic nonmalignant pain. The availability of oxycodone preparations has increased its clinical use exponentially during the last decade. Further clinical studies are still needed to fully understand its clinical pharmacology. Oxycodone is still a new 'old' drug whose pharmacology and clinical potential is not yet fully understood.

Effect of vaginal administration of controlled-release oxycodone on cancer pain

Controlled-release oxycodone is an orally administered strong opioid analgesic for moderate to severe cancer pain. Sometimes, its oral administration has to be stopped because of continuous nausea, vomiting, conscious disturbance, or inability to swallow. This study was to investigate analgesic effect of vaginal administration of controlled-release oxycodone on cancer pain and observe adverse events to provide a new choice for female patients who can not tolerate the adverse events caused by oral administration. Controlled-release oxycodone tablets were vaginally administered to 36 female patients with moderate to severe cancer pain. The initial dose was 10 mg every 12 h to patients who had never taken opioid analgesics; former dose continued to patients switching to vaginal route from oral route. Among the 36 patients, six had complete relief of cancer pain, 20 had significant relief, four had moderate relief, and four had slight relief, two had no relief. The relief rate of cancer pain was 83.3%. The mean time for onset of analgesic effect was 49 min; the mean duration of analgesic effect was 13.8 h. Main adverse event was vaginal burning sensation in nine (25.0%) patients. No patient discontinued vaginal administration because of adverse events. The vaginal administration of controlled-release oxycodone is a safe,effective and simple means of managing cancer pain in female patients who can not tolerate the adverse events caused by oral administration.

Alleged Medical Abandonment in Chronic Opioid Analgesic Therapy: Case Report

The objectives of this medicolegal case report were the following: 1) present details of a chronic pain patient (CPP) on chronic opioid analgesic therapy (COAT), who diverted her opioids and was terminated from treatment, and subsequently committed suicide; 2) present both the plaintiff's and defendant's (the COAT prescriber) expert witnesses' opinions as to the allegation of medical abandonment of this patient and other allegations; and 3) based on these opinions, to develop some recommendations as to how pain physicians can minimize their medicolegal risk when termination of the physician-patient relationship is warranted. This is a case report of a CPP treated by a pain physician who demonstrated aberrant drug-related behaviors and required large doses of controlled-release oxycodone. Differences between the plaintiff's and defendant's experts' opinions are presented by utilizing the COAT literature. Options for avoiding allegations of abandonment are proposed. To avoid and protect themselves against potential abandonment allegations when termination of the physician-patient relationship is warranted, physicians are advised to consider following the outlined procedures.

Development of a budget-impact model to quantify potential cost savings from prescription opioids designed to deter abuse or ease of extraction

Prescription opioid (RxO) abuse, dependence and misuse is a significant and growing problem in the US, and is associated with a substantial economic burden. Such abuse may be reduced by theoretical formulations that minimize the possibility of abuse, dependence and misuse of RxOs by injection, snorting, crushing or chewing. As well as public health and safety benefits, use of an abuse-deterrent/resistant RxO (ADO) that may deter abuse, dependence and misuse could also generate cost savings. To estimate potential annual cost savings to US third-party payers realized from introducing a theoretical ADO. A budget-impact model (BIM) was developed to assess potential cost savings from the introduction of an ADO to third-party payers. The BIM included information on ADO attributes, costs associated with RxO abuse-related episodes, prevalence of RxO abuse and potential market share capture of the new ADO. Numbers of abuse-related episodes were calculated using a database on admissions to substance abuse treatment centres and other national surveys. Direct (medical and pharmaceutical) costs associated with RxO abuse, dependence and misuse were calculated using de-identified employer claims data (n > 6 000 000) for costs of abuse-related episodes. All cost estimates are in $US, year 2006 values. The BIM was developed for a theoretical prescription drug with therapeutic properties similar to those of controlled-release oxycodone, in a formulation that is specifically designed to resist or deter common methods of abuse, including injection, crushing, snorting and chewing. Potential cost savings to third-party payers from introducing an ADO for the US (assuming a privately insured cost structure) could range from approximately $US0.6 billion to $US1.6 billion per year depending on different possible scenarios. While savings estimates from introduction of an ADO depend on a range of assumptions, cost savings would be substantial.

OxyContin® Abuse and Overdose

Background: OxyContin® (controlled-release oxycodone hydrochloride) (Purdue Pharma, Stamford, CT) was approved in 1995 by the US Food and Drug Administration (FDA) for moderate-to-severe chronic pain. Crushing and snorting the delayed-release tablets results in a rapid release of the drug, increased absorption, and high peak serum concentrations. The propensity for addiction to OxyContin® and the trend of increased prescription drug abuse have made it imperative for physicians and health care providers to recognize the clinical presentation of overdose and know how to manage associated complications. Objectives: In this review of OxyContin®, we discuss current trends in its abuse and the clinical presentation of overdose. We review the specific effects of the drug on body systems and the recognition of symptomatology, differential diagnosis, and management. Discussion: Many of the clinical findings in acute opioid overdoses are nonspecific, making diagnosis difficult. OxyContin® overdose presents with a typical opiate toxidrome, including decreased respirations, miosis, hypothermia, bradycardia, hypotension, and altered mental status. The presence of coingestants can cloud the clinical picture. If OxyContin® overdose is suspected, early ventilation and oxygenation should be administered, which is generally sufficient to prevent death. Even in the absence of a confirmation, cautious administration of naloxone–the opiate receptor antagonist and antidote for opioid overdoses–may have both diagnostic and therapeutic effects. Summary: With increasing rates of prescription drug abuse, OxyContin® will continue to present challenges to physicians and health care providers. Physicians should be aware of potential patients who are seeking OxyContin® for recreational use.

A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster

Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health-related quality of life, there have been no randomized clinical trials of oral medications specifically for its ongoing treatment. A randomized clinical trial was conducted in which 87 subjects ⩾50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24 h ⩾ 3 on a 0–10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled-release (CR) oxycodone, gabapentin, or placebo. Subjects were evaluated for adverse effects of treatment, acute pain, and health-related quality of life. The results showed that CR-oxycodone and gabapentin were generally safe and were associated with adverse events that reflect well-known effects of these medications. Discontinuing participation in the trial, primarily associated with constipation, occurred more frequently in subjects randomized to CR-oxycodone (27.6%) compared with placebo (6.9%). Treatment with CR-oxycodone reduced the mean worst pain over days 1–8 ( p = 0.01) and days 1–14 ( p = 0.02) relative to placebo but not throughout the entire 28-day treatment period as pain resolved in most subjects. Gabapentin did not provide significantly greater pain relief than placebo, although the data for the first week were consistent with a modest benefit. By demonstrating that CR-oxycodone is safe, generally adequately tolerated, and appears to have efficacy for relieving acute pain, the results of this clinical trial provide a foundation for evidence-based treatment for acute pain in herpes zoster.

Controlled-Release Oxycodone and Pregabalin in the Treatment of Neuropathic Pain: Results of a Multicenter Italian Study

Aims: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. Materials and Methods: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). Results: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy (reduction in NRS value: 80, 76, and 46%, respectively; p ≤ 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy (p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been ‘effective’ or ‘very effective’. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. Conclusions: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation.