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PURPOSE/OBJECTIVES To determine the severity and trajectory of constipation among patients with cancer from opioids and/or vinca alkaloids. DESIGN Exploratory, descriptive. SETTING Moffitt Cancer Center, a National Cancer Institute-designated comprehensive cancer center in Tampa, FL. SAMPLE 400 patients at risk for developing medication-induced constipation from opioids, vinca alkaloids, or both. METHODS Patients' baseline data included the Constipation Assessment Scale (CAS), the constipation item from the Memorial Symptom Assessment Scale (MSAS) for intensity and distress, and the laxative interview. Following the interview, the medical chart was reviewed for clinical and demographic data. Patients were asked about constipation (CAS) and laxatives consumed (laxative interview) during eight weekly telephone calls. MAIN RESEARCH VARIABLES Constipation presence, intensity, and distress. FINDINGS At baseline, 63% of patients reported some level of constipation. During the eight weeks, constipation fluctuated with scores ranging from 0-16, with the opioid-only group showing a small but statistically significant decrease in intensity. Constipation intensity and distress on the MSAS were significantly correlated (r = 0.76; p = 0.000). CONCLUSIONS The majority of the sample reported constipation that ranged from mild to severe, persisted over time, and caused symptom distress. Therefore, healthcare providers in the cancer center likely were neither adequately managing the medication-induced constipation nor apparently teaching patients to manage it themselves. IMPLICATIONS FOR NURSING National Comprehensive Cancer Network guidelines support the importance of managing medication-induced constipation. However, guidelines are not being followed in many cases; therefore, more focus is needed on constipation in clinical and educational settings as well as more research. KNOWLEDGE TRANSLATION Patients receiving opioids and vinca alkaloids are at risk of constipation. Currently, medication-induced constipation is poorly managed. Managing constipation may lessen symptom distress, thereby improving quality of life in these patients.

Background Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a μ-opioid–receptor antagonist, has restricted ability to cross the blood–brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. Methods A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. Results In the methylnaltrexone group, 48% o...

Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a 3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.

9081 Background: Constipation is a common and distressing side effect of opioid treatment particularly in patients with cancer. Two phase 3 trials (Studies 301 and 302) reported that subcutaneous (SC) methylnaltrexone was well tolerated and effective in inducing laxation in patients with advanced illness with opioid-induced constipation (OIC) while maintaining central analgesia. Aims: To evaluate improvement in constipation in cancer patients treated with methylnaltrexone in the above studies. Methods: In Study 301, 124 cancer patients received a single dose of methylnaltrexone (SC 0.15mg/kg, 0.30mg/kg) or placebo. In Study 302, 78 cancer patients received either 0.15mg/kg SC QOD methylnaltrexone for 2 weeks (total of 7 doses) or placebo. Patients had a life expectancy of 1–6 months, no laxation within 48 hours, and were maintained on stable opioids and baseline laxatives. The primary efficacy endpoints were laxation within 4 hours after a single or first dose of study drug and laxation within 4 hours for at least 2 of the first 4 doses (Study 302). The secondary endpoints were laxation within 24 hours, pain scores, and opioid withdrawal symptoms. Results: A majority of the methylnaltrexone-treated cancer patients had a laxation within the first 4 hours of study drug administration ( Table ). There were no clinically significant changes in pain scores or opioid withdrawal symptoms. Conclusions: Our results demonstrate that in cancer patients with advanced illness and OIC, methylnaltrexone significantly improved constipation, without loss of pain control or opioid withdrawal. [Table: see text] No significant financial relationships to disclose.