methylnaltrexone and Abdominal-Pain

Methylnaltrexone is a selective peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioids without affecting centrally mediated analgesia. In two double-blind, placebo-controlled, Phase III studies of methylnaltrexone for opioid-induced constipation in patients with advanced illness, abdominal pain was the most common adverse event (AE) reported.. This analysis sought to further characterize the Medical Dictionary for Regulatory Activities-defined abdominal pain AEs experienced in these studies.. A post hoc analysis of verbatim descriptions was used to further assess AEs characterized as abdominal pain in both trials. Descriptive summary statistics were used to assess severity of abdominal pain, effect of abdominal pain on global pain scores, and other characteristics. Logistic regression analysis was used to determine the association of baseline characteristics with abdominal pain.. Most verbatim descriptions of abdominal pain referred to "abdominal cramps" or "cramping." Abdominal pain AEs were mostly mild to moderate in severity and did not affect patients' global evaluation of pain. The incidence of abdominal pain AEs in methylnaltrexone-treated patients was greatest after the first dose and decreased with subsequent doses. No association between abdominal pain AEs and most baseline patient characteristics was noted.. Abdominal pain AEs in methylnaltrexone-treated patients in clinical trials are usually described as "cramps" or "cramping," are mostly mild to moderate in severity, and decrease in incidence with subsequent dosing.

Topics: Abdominal Pain; Adult; Aged; Analgesics, Opioid; Colic; Constipation; Double-Blind Method; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Pain Measurement; Quaternary Ammonium Compounds

Topics: Abdominal Pain; Analgesics, Opioid; Child; Constipation; Critical Illness; Defecation; Humans; Infant; Laxatives; Male; Morphine; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Treatment Outcome

Topics: Abdominal Pain; Adult; Analgesics, Opioid; Anorexia; Chronic Disease; Diabetes Mellitus, Type 1; Drug Administration Schedule; Endoscopy, Gastrointestinal; Gastroparesis; Humans; Hypertension; Kidney Failure, Chronic; Male; Naltrexone; Narcotic Antagonists; Nausea; Neuralgia; Quaternary Ammonium Compounds; Substance Withdrawal Syndrome; Treatment Outcome; Vomiting

Narcotic bowel syndrome (NBS) describes disabling chronic severe abdominal pain that worsens despite continuing or escalating doses of opiates. Therapy is very limited.. To examine effects of blocking peripheral µ-opioid receptors on the symptomatology of patients with NBS and its safety.. An open-label observational study was performed in four women with NBS. After a 2-week run-in period, patients were treated for 12 weeks with 8-12 mg methylnaltrexone bromide subcutaneously every other day, increasing to daily if there was poor response. Patient and physician assessment was documented, and patients completed an eight-symptom visual analogue scale weekly and the Functional Assessment of Chronic Illnesses Therapy-Fatigue questionnaire for fatigue. Patients were observed for 4 weeks following withdrawal of the drug.. One patient was unable to tolerate the study medication because of worsening pain after injection, and withdrew. Two showed clear benefit with reduction of symptoms overall, pain, bloating, distension, nausea and tiredness, with improved satisfaction and consistency of bowel actions and fatigue scores. Both reduced analgesic usage. The third had improved ileostomy output and had no episodes of severe bloating, but pain scores remained high. All three worsened after drug withdrawal and requested retreatment. Three experienced abdominal pains of moderate severity for 30-60 min consistently within 5 min of each injection. No other adverse events were experienced.. Methylnaltrexone has a positive impact on symptoms in women with NBS, although treatment does induce transient pain following its administration. Larger studies are required to examine its efficacy and longer term safety in this patient group.

Topics: Abdominal Pain; Adult; Female; Humans; Middle Aged; Naltrexone; Narcotic Antagonists; Narcotics; Pilot Projects; Prospective Studies; Quaternary Ammonium Compounds; Syndrome; Treatment Outcome