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| |  Methylnaltrexone Improves Symptoms in Patients With Opioid-Induced Constipation: Presented at CDDW By Cameron Johnston TORONTO -- March 4, 2010 -- Subcutaneous methylnaltrexone is effective for relieving opioid-induced constipation in patients with advanced illnesses who require large doses of pain medication, researchers said here on March 1 at the Canadian Digestive Diseases Week 2010 (CDDW). However, side effects including abdominal cramping and flatulence can be considerable, although not enough to limit the patient’s use of the analgesic. Robert Israel, MD, Progenics Pharmaceuticals Inc., Tarrytown, New York, discussed the latest findings stemming from 2 phase 3 studies in which patients received either methylnaltrexone or placebo to deal with constipation caused from opiate use. The trials recruited 110 patients to receive subcutaneous (SC) methylnaltrexone 0.15 mg/kg and 55 patients to receive 0.30 mg/kg every other day, as well as 123 patients who would receive a placebo. Of the patients, 80% had cancer, 5% had cardiac disease, and 15% had other illnesses necessitating continuous, daily high-dose opioid analgesics. According to Dr. Israel, many of these patients were receiving palliative care and so needed special care to ensure that they were kept as comfortable as possible. In the first analysis, 48% of patients experienced laxation and resumed more or less normal bowel-voiding function within 4 hours of their first SC injection of the study drug, compared with 15% who received a placebo. Among patients who had received at least 2 doses of methylnaltrexone out of a planned 4 doses, 52% had laxation within 4 hours compared with 8% of those who received a placebo. Although this phase of the trials confirmed the utility of methylnaltrexone in helping alleviate opioid-induced constipation, it was felt helpful to determine patient perceptions of the drug. Therefore, a further post hoc analysis was conducted, in which standardised descriptive terms and definitions taken from the Medical Dictionary for Drug Regulatory Affairs were used to categorise the patients’ experiences. Abdominal pain was reported by 23.6% of patients in the low-dose therapy and 38.2% of patients in the high-dose methylnaltrexone, for an overall incidence rate of 28.5%. This compared with 9.8% of patients who received the placebo. Patients actually described their symptoms more as “abdominal cramping” rather than pain however, with 24.2% overall using the more specific term. This compared with 6.5% of patients who received the placebo. There were no discontinuations due to the adverse events in 1 study, and 2 discontinuations in the second phase 3 study. However, 2.1% of patients in the low-dose arm and 3.6% in the high-dose arm said the abdominal pain was “severe”. This compared with 1.9% of patients who received the placebo and reported severe abdominal pain. Dr. Israel pointed out that there were no differences in reports of abdominal pain between the groups according to age, race, cancer status, time without a bowel movement prior to therapy, opioid use, or pain scores. Nor did World Health Organization performance status have an impact on their outcomes. Most of the reports of abdominal cramping and pain occurred after the first treatment, and dissipated with subsequent injections of the methylnaltrexone. There were, in fact, half as many reports of abdominal pain following the second injection as there were following the first injection. Funding for this study was provided by Progenics Pharmaceuticals Inc. CDDW is the annual scientific conference of the Canadian Association of Gastroenterology (CAG) and the Canadian Association for the Study of the Liver (CASL). [Presentation title: Characterization of Gastrointestinal Adverse Events With Methylnaltrexone Treatment in Patients With Advanced Illness and Opioid-Induced Constipation: A Post Hoc Analysis. Abstract 183]
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