Fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic cancer and noncancer pain: a randomized, double-blind, crossover study followed by a 12-week open-label phase to evaluate patient outcomes.

OBJECTIVE: Evaluate analgesic efficacy, functional benefit, and patient satisfaction with fentanyl buccal tablet vs immediate-release oxycodone for breakthrough pain (BTP). DESIGN: Randomized, double-blind, active-controlled crossover trial and 12-week open-label extension. SETTING: Forty-two U.S. sites. PATIENTS: Opioid-tolerant patients with predominantly chronic noncancer pain experiencing BTP. INTERVENTION: Patients were randomized to open-label titration periods with fentanyl buccal tablet followed by oxycodone or vice versa for BTP management. After titrating to a successful dose of both medications (single dose providing adequate analgesia without unacceptable adverse events), patients were re-randomized to treat 10 BTP episodes with one medication and 10 with the other. OUTCOME MEASURES: The primary efficacy measure was pain intensity (PI) difference 15 minutes postdose. Secondary measures included PI difference 5, 10, 30, 45, and 60 minutes postdose; sum of PI differences 30 and 60 minutes postdose; ≥33% and ≥50% reduction in PI; and pain relief. Questionnaires assessed functional status/satisfaction. RESULTS: Of 213 patients enrolled, 149 achieved a successful dose of both medications; 131 completed the double-blind phase and 112 the open-label phase. PI difference at 15 minutes (mean [standard deviation]) was greater with fentanyl buccal tablet (0.88 [1.20]) vs oxycodone (0.76 [1.13]; P < 0.001). Patients preferred fentanyl buccal tablet (47%) over oxycodone (35%); 18% had no preference. Patients and clinicians reported consistently better functional improvement and satisfaction with fentanyl buccal tablet vs short-acting opioids (P < 0.05). CONCLUSIONS: Fentanyl buccal tablet was associated with rapid onset of analgesia and improvements in functional status and patient satisfaction compared with immediate-release oxycodone.

Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain.

OBJECTIVE: Several prominent guidelines recommend that patients on long-term opioid therapy have periodic urine drug monitoring (UDM) for appropriate use; however, none address the specific questions of which patients to test, which substances to test for, how often to test, and how to act on the results. DESIGN: In the absence of adequate scientific evidence in the literature, a panel of experts in the field of pain and addiction medicine was convened to develop consensus UDM recommendations. The panel met three times between March 2010 and April 2011, and reviewed several drafts of the recommendations document between meetings. RESULTS: The group was able to achieve consensus on a set of UDM recommendations addressing test selection, test frequency, interpretation of results, and how to handle discrepancies based on specific results. CONCLUSION: While the participating panel members recognize that there currently is a limited evidence base to support the expert panel's recommendations, primary care providers and pain specialists are largely acting today based on anecdote, intuition, and individual experience. The recommendations are meant to begin to provide a framework for standardizing practices for UDM in the treatment of chronic pain, and to serve as a catalyst to advance research that quantifies the effects of UDM on opioid therapy management and patient outcomes.

Left stellate ganglion blockade for the management of drug-resistant electrical storm.

BACKGROUND: Electrical storm (ES) is a syndrome characterized by rapidly recurrent ventricular fibrillation or tachycardia. The most common precipitants include ongoing or recent myocardial ischemia, exacerbating congestive heart failure, arrhythmogenic medications, and electrolyte disturbances. OBJECTIVE: We describe the case of a patient who developed ES seventy-two hours status post triple vessel coronary artery bypass grafting that did not respond to conservative treatment and required approximately 70 electrical shocks. CONCLUSION: The patient was rapidly stabilized following left stellate ganglion blockade.

Primary care physician opinion survey on FDA opioid risk evaluation and mitigation strategies.

INTRODUCTION: In response to disturbing rises in prescription opioid abuse, the Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS) that will require prescribers to obtain mandatory education, provide mandatory patient education, register patients into registries, and so forth before prescribing certain opioids. The first opioid to be subject to the new REMS was the recently approved fentanyl buccal soluble film (Onsolis). The FDA plans to extend mandatory REMS to other opioids, including all rapid-onset formulations and eventually all long-acting opioids, whether or not they already have FDA approval. To assess the likely impact of REMS on opioid prescribing, the authors conducted a survey of how REMS implementation might affect opioid prescribing. METHODS: After obtaining Institutional Review Board's approval, a survey regarding opioid prescribing was sent via e-mail to 2,800 physician members of the Pennsylvania Academy of Family Physicians. Practicing family practice physicians were asked to respond to questions regarding their current opioid prescribing, and how various components of REMS might alter their future opioid prescribing. RESULTS: A total of 259 surveys were completed. Of the 259 physicians who responded, 87 percent reported themselves as being primary care practitioners; others identified themselves as specialists. Of all respondents, 96 percent currently prescribe opioids for acute pain, 77 percent for cancer pain, and 83 percent for chronic nonmalignant pain. The respondents were split from 52 percent to 48 percent in terms of being in an urban versus a rural practice setting. Forty eight percent of all respondents reported their willingness to complete no more than 2 hours of training if it were available locally to be able to continue prescribing opioids. A similar percentage (50 percent) also said that they would encourage patient compliance with education and register their patients on a 6-month basis. However, the following percent of respondents reported that they would discontinue prescribing an opioid product if required to comply with the following REMS requirement: obtain 4-8 hours of straining, followed by 2 hours of pain-related continuing medical education every 2 years (13.4 percent); complete mandatory patient education (12.2 percent); document ongoing monitoring of therapy including efficacy, safety, and monitoring for aberrant drug-related behavior (10.4 percent); or register each patient in a patient registry, and have the patient re-registered every 6 months (18.3 percent). CONCLUSIONS: The results suggest that 50 percent of the responding physicians would be willing to comply with the mandatory education component of REMS, including the requirement to provide education to patients. For some REMS components, willingness to continue to prescribe despite the restriction was higher (up to 90 percent). However, this leaves a substantial proportion of physicians who would not be willing to prescribe opioids controlled by the new REMS, which could have the unintended effect of decreasing access to these medications for legitimate medical purposes.

The efficacy and safety of fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic pain.

BACKGROUND: Current clinical guidelines have identified the need for studies comparing the effect of different short-acting or rapid-onset opioids for the treatment of breakthrough pain (BTP). In this study we evaluated the efficacy and safety of treatment with fentanyl buccal tablet (FBT) in comparison with immediate-release oxycodone in alleviating BTP in opioid-tolerant patients with chronic pain. METHODS: In this cross-over design study, opioid-tolerant patients were randomized to open-label titration with FBT (200, 400, 600, 800 µg) followed by oxycodone (15, 30, 45, 60 mg) or vice versa for the management of BTP. After titration to a successful dose of both study drugs, patients were rerandomized to double-blind treatment for 10 BTP episodes with 1 of the already identified successful doses of study drug followed by cross-over to double-blind treatment for 10 BTP episodes with the other study drug. The primary efficacy measure was the difference in pain intensity (based on an 11-point numerical scale) 15 minutes after administration of study drug (PID(15)). Other efficacy measures included PID at other time points postdose (5 through 60 minutes), the sum of pain intensity differences (SPID) at 30 and 60 minutes postdose, pain relief (5 through 60 minutes), proportion of BTP episodes for which patients experienced meaningful reduction in pain intensity, and patient preference for BTP medication. Adverse events were also recorded. RESULTS: Of the 323 patients enrolled, 203 achieved a successful dose of both study drugs, 191 completed the titration phase, and 180 completed the double-blind phase. PID(15) was significantly greater after FBT versus oxycodone (mean [SD], 0.82 [1.12] vs. 0.60 [0.88]; 95% confidence interval [CI] = 0.18, 0.29; P < 0.0001). Secondary efficacy measures favored FBT and showed differences versus oxycodone from 5 minutes postdose for PID and 10 minutes postdose for pain relief. SPID(30) and SPID(60) were greater with FBT than with oxycodone (P < 0.0001 for both measures). A ≥33% improvement in pain intensity occurred in a larger proportion of FBT-treated episodes versus oxycodone beginning 15 through 45 minutes postdose (P < 0.05). FBT was preferred by 52% of patients, oxycodone by 33%. Adverse events with both study drugs were generally typical of opioids, and the majority occurred during titration. Two serious adverse events (pneumonia) were reported in 1 patient; both occurrences were considered unrelated to study drug. CONCLUSION: FBT resulted in more rapid onset of analgesia and was generally well tolerated in comparison with oxycodone for the treatment of BTP in opioid-tolerant patients.