Differences in rapid-acting opioid dosage forms for cancer-related BTP: a review of comparative effectiveness studies

s The Journal of Pain P5 (116) Differences in rapid-acting opioid dosage forms for cancer-related BTP: a reviewof comparative effectiveness studies S Strassels and H Chandwani; University of Texas at Austin , Austin, TX We sought to review the published, English-language biomedical literature on comparisons between dosage forms of rapid-onset opioids used for the pharmacotherapy of cancer-related breakthrough pain (BTP). We searched PubMed, CINAHL, the Cochrane Library, and the Cochrane Central Register of Controlled Trials to identify studies of these drugs in humans. The search string used was ‘[(breakthrough pain AND cancer) AND (randomized clinical trial OR cohort OR case-control OR pharmacotherapy)]’. Bibliographies of identified papers were hand-searched to identify additional relevant studies. Meeting abstracts, letters to the editor, treatment guidelines, expert opinion, and narrative reviews were excluded. We found 3 studies that compared different dosage forms of the same opioid. In a multi-center, open-label, randomized, crossover study (n = 139) of oral transmucosal fentanyl citrate (OTFC) and intranasal fentanyl spray (INFS), INFS provided faster pain relief (median (min): 11 vs. 16), was preferred by more patients (p < 0.001), and resulted in $33% reduction in pain intensity 5 minutes postdose compared to OTFC (25.3% of cases vs. 6.8% of cases; p < 0.001). In the 2nd study, investigators found no difference in pain outcomes (time to maximum effect, maximum effect, tolerability of drug product) in a double blind, placebo-controlled, crossover, randomized trial of OTFC in a sweetened matrix against OTFC in a compressed powder formulation in head and neck cancer patients with radiation-induced oral mucositis (n=14). Last, in a comparison of effervescent (EM) and regular-release oral morphine (RM), within-group pain intensity scores were statistically significantly reduced with both preparations from baseline pain (EM: 7.8/10 to 3.2/ 10, p < 0.001; RM not shown). These analyses contribute to the understanding of cancer-related BTP management, but also indicate the presence of a gap in knowledge about comparative effectiveness of different dosage forms of rapid-acting opioids. Supported in part by Meda Pharmaceuticals. (117) Pharmacotherapy of cancer-related breakthrough pain: a review of drug-drug comparisons S Strassels and H Chandwani; University of Texas at Austin, Austin, TX The purpose of this study was to assess the published, English-language biomedical literature on comparative effectiveness between drugs for management of cancer-related breakthrough pain (BTP) in humans. We conducted a systematic literature review using PubMed, CINAHL, the Cochrane Library, and the Cochrane Central Register of Controlled Trials for all years available. The search strings usedwas ‘[breakthrough pain AND cancer AND (randomized clinical trial OR cohort OR case-control OR pharmacotherapy)]. The bibliographies of all identified papers were hand-searched to identify additional relevant studies. Meeting abstracts, letters to the editor, treatment guidelines or recommendations, expert opinion, and narrative reviews were excluded. We identified only three papers that met the inclusion criteria; all three were carried out in a palliative care unit. In an open-label, randomized, crossover study (n = 25; 53 pairs of BTP episodes) comparing intravenous morphine (IV-MO) to oral transmucosal fentanyl citrate (OTFC), IV-MO significantly reduced pain intensity (10-point scale) 15 minutes post-dose compared to OTFC (6.9 to 3.3 vs. 6.9 to 4.1; p = 0.013); there was no significant difference in pain intensity 30 minutes post dose (p = 0.059). The adverse events profile for both drugs was similar. A prospective cohort study of various drugs and dosage forms (n=66) found that a rescue dose one-fifth of the oralmorphine equivalent of the usual opioid dose was safe and effective, irrespective of drug and route of administration; pain intensity 15 minutes post-dose was significantly lower (p < 0.001) for all formulations. Last, in two opioid-tolerant individuals with bone metastases, burst ketamine in addition to OTFC was judged to be helpful, although no formal analysis was done. We found few and inconclusive studies comparing pharmacotherapy for cancer-related BTP, which might lead to suboptimal guidance of therapeutic choices. Supported in part by Meda Pharmaceuticals. (118) Rates of inappropriate drug use in the chronic pain population: an update K Bronstein, J Dhaliwal, and H Leider; Ameritox, Inc., Baltimore, MD With increasing misuse and abuse of controlled substances, urine drug monitoring is an important method to assess patients’ compliance with medication regimens and to identify patients using illicit substances. Urine samples tested by Ameritox between October 1, 2009 and October 1, 2010 were reviewed for overall results as well as illicit use. Samples were evaluated (using a proprietary methodology) to assess the likelihood that the patients were taking their medications as prescribed. 922,440 samples were tested during this period. Eleven percent of the samples were found to have illicit drugs present, 31%weremissing the prescribed drug, 29% had a drug present that was not on the requisition accompanying the sample, 15% were found to have normalized values above the expected range, and 18% were below the expected range. Only 31%of samples were considered to be normal, defined as: No illicit or non-prescribed drugs present, confirmed presence of prescribed medications, and normalized urine values within the expected range. Of the 104,905 samples that were found to have illicit drugs present, marijuana was the most common (81,983), followed by cocaine (22,367), andmethamphetamines (5,926). The remainderswere found to have various other drugs including heroin, ecstasy, and PCP. Comparison of these data with a previous study (Couto, 2009) of 938,420 samples shows that the rates of illicit drugs found, medications found that were not on the requisition, and samples missing the prescribed medication have remained relatively stable. The incidence of patients likely taking their medications as prescribed rose from 25.5% to 31.2%. This study shows inappropriate drug use remains prevalent in the population of chronic pain patients. In spite of the increasing focus to use risk assessment methods in order to reduce the numbers of patients misusing their medications, urine drug testing results show that the incidence remains relatively stable. (119) Pain medication monitoring using urine drug testing in an internal medicine practice: can it impact clinical decisions? K Bronstein and S Rafique; New Snellville Clinic, Snellville, GA Guidelines on the use of chronic opioid therapy in non-cancer pain outline the need for urine drug testing (UDT). For clinicians not primarily focused on pain management, performing UDT in a small number of patients may not be a priority. However, with increasing drug abuse andmisuse, it seems imperative ALL physicians prescribing controlled substances monitor patients receiving these medications. To this end, the New Snellville Clinic, an internal medicine practice, began UDT all patients on chronic pain and psychotropic medications. In addition, as a part of the testing protocol, the clinic makes an assessment of the risk of the patient misusing their medication based on past medical and social history, aberrant behaviors, requests for early refills or the need for escalating doses of medication in order to control pain. To date 41 patients had UDT performed. Results were normal in only 17 patients, meaning these patients did not have an illicit present and they were likely to be taking their medications as prescribed. For the patients with abnormal results, 10 had drugs found that were not prescribed by the clinic, 8 did not have the prescribed pain medication present in their urine, 9 patients had drug levels that were inconsistent with their prescribed doses using a proprietary methodology, and 2 patients had illicit drugs present. Comparing UDT results with assessments of risk, 12 out of 26 patients who were not thought to be at risk had an abnormal urine test. In those patients thought to be at risk for medication misuse 11 out of 14 had an abnormal urine test. These results, while from a single practice, illustrate the need for urine drug testing in all patients on chronic controlled medications. Even clinicians who only have a limited number of chronic pain patients need to monitor medication adherence.