Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).

Background: Subcutaneous methylnaltrexone, a peripherally acting l-opioid receptor antagonist, improves opioid-induced constipation (OIC) in patients with chronic noncancer pain. An oral methylnaltrexone formulation has been developed. Methods: In this phase 3, double-blind trial, adults with chronic noncancer pain receiving opioid doses of ≥ 50 mg/ day oral morphine equivalents with OIC were randomly assigned to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily (QD) for 4 weeks followed by as-needed dosing for 8 weeks. Patients who had ≥ 3 rescue-free bowel movements (RFBMs)/week, with an increase of ≥ 1 RFBM/ week from baseline for ≥ 3 of 4 weeks during the QD period, were responders. Results: Overall, 803 patients were included in the analyses. A significantly greater percentage of patients had an increase in mean percentage of dosing days resulting in an RFBM within 4 hours of dosing during weeks 1 through 4 (QD period; primary endpoint) with methylnaltrexone (300 mg/ day [24.6%; P = 0.002] and 450 mg/day [27.4%; P < 0.0001]) vs. placebo (18.2%). The percentage of responders (49.3% for 300 mg [P = 0.03] and 51.5% for 450 mg [P = 0.005] vs. 38.3% with placebo) and change from baseline in mean number of weekly RFBMs (difference vs. placebo, 0.5 for 300 mg [P = 0.03] and 0.5 for 450 mg [P = 0.02]) was significantly greater with methylnaltrexone 300 and 450 mg/day vs. placebo during the QD period. All dosages of oral methylnaltrexone were well tolerated. Conclusions: Oral methylnaltrexone was efficacious and well tolerated for OIC in patients with chronic noncancer pain, particularly the 450-mg dose. &

The variability in de novo clinical response to opioids likely represents the interaction of the varying properties of the individual opioids with the variability in individual patient biology. This interaction forms the rationale for opioid switching and explains its clinical utility. As with opioid switching, success with opioid rotation is related to the myriad of factors determining an individual patient's response to a specific opioid. However, the benefits of opioid rotation also derive from a partial reversal of tolerance at the mu-opioid receptor and the response of different micro-opioid receptor subtypes to the different opioids.

Cancer patients stabilized on morphine CR or oxycodone CR were safely and rapidly converted to a lower milligram dose of oxymorphone ER that provided adequate pain relief with comparable tolerability. These results justify additional trials with oxymorphone ER.

A B S T R A C TKetamine oral rinse provided effective palliation of intractable mucositis pain in a 32-year-old woman with squamous carcinoma of the tongue undergoing radiation therapy. Pain at rest and with eating decreased with ketamine, allowing for a tapering of her opiate dose. No side effects of ketamine were reported. Treatment benefits most likely arose from the inhibition by ketamine of peripheral N-methyl D-aspartate receptors, though other mechanisms of action may have been contributory. Further evaluation of topical ketamine in the treatment of mucositis-related pain, and, potentially, other causes of inflammatory oral pain, are warranted.