[Show abstract][Hide abstract]ABSTRACT: To determine the number of steps and identify characteristics associated with attaining a stable dose of morphine sulfate and sequestered naltrexone extended release capsules (MS-sNT).
Data from an open-label, long-term multicenter study designed to assess the safety of MS-sNT for managing chronic (≥ 3 m), moderate-to-severe pain were analyzed post hoc. Initial MS-sNT dose was 20 mg twice daily (BID) for opioid-naïve patients and 50% to 75% of current daily opioid dose for opioid-experienced patients. Dose adjustments upward/downward were allowed throughout the study with ≥ 3 days between increases; opioid-experienced patients could increase ≥ 24 hours after initial drug dispensing. Nonopioid analgesics were permitted as rescue medication. Stable dose was defined post hoc as one maintained for 2 consecutive study visits.
Overall, 69% of patients (n = 319/465) achieved a stable dose; 85% (n = 272) achieved a stable dose in ≤ 2 titration dose adjustments or "steps," and 96% (n = 305) achieved a stable dose in ≤ 4 steps. The mean time to stable dose was 28.9 days (standard deviation [SD], 34.1 days); the median was 12 days. A stable dose was achieved in 70% (118/168) of opioid-naïve patients (mean, 24.2 days [SD, 33.4 days]; median, 8 days) and 68% (201/297) of opioid-experienced patients (mean, 31.7 days [SD, 34.3 days]; median, 25 days). A stable dose was achieved by 79% (19/24) of patients who previously used morphine, 64% (27/42) who used oxycodone, 59% (47/79) who used hydrocodone, and 71% (83/117) who used multiple opioids. Baseline pain scores were similar between patients who did and did not achieve a stable dose. At the time of stable dose achievement, average, least, worst, and current pain were all decreased from baseline.
The study provides information about anticipated rates of achieving stable opioid dose in patients who received MS-sNT for up to 1 year to manage chronic, moderate-to-severe pain. Both opioid-naïve and opioid-experienced patients achieved a stable dose of MS-sNT, generally in ≤ 2 steps. Opioid experience and previous opioid use may influence ability to achieve a stable dose and number of steps required. More studies are needed on the anticipated experience of opioid titration/conversion to help physicians and patients set expectations for initiation of and conversion between opioid therapies.
[Show abstract][Hide abstract]ABSTRACT: Morphine sulfate and naltrexone hydrochloride extended release capsules contain extended-release pellets of morphine with a sequestered naltrexone core (MS-sNT). Taken whole, as intended, morphine is released to provide pain relief; if tampered with by crushing, naltrexone is released to mitigate subjective effects of morphine.
This open-label study assessed long-term (12-month) safety of MS-sNT in patients with chronic, moderate to severe pain.
Safety assessments included determining adverse events (AEs), laboratory assessments, and the Clinical Opiate Withdrawal Scale (COWS). Analgesic efficacy was assessed (diary) as worst, least, average, and current pain using an 11-point numeric scale (0=none; 10=worst).
Of 465 patients receiving one or more doses, 160 completed the study. Most patients (81.3%) experienced one or more AEs, most commonly constipation (31.8%) or nausea (25.2%). Thirty-three patients (7.1%) reported serious AEs; one patient's severe gastrointestinal inflammation and colitis were considered possibly study drug-related. Most discontinuations (30%) occurred in the first month, most often because of AEs (23.7%). There were no clinically relevant changes in laboratory results or vital signs, and no clinically significant electrocardiogram changes deemed study drug-related. During each visit after Week 1, 5% or fewer patients had COWS scores indicating mild withdrawal symptoms (range, 0%-4.8%). Five patients, who did not take the study drug as instructed, had scores consistent with moderate withdrawal. MS-sNT yielded statistically significant improvements from baseline in mean scores for all pain diary items for all visits, except Week 1 for least pain.
In this study population, when MS-sNT was taken as directed for chronic, moderate to severe pain for up to 12 months, most AEs were typical opioid-related side effects. Mean COWS scores remained low, indicating lack of withdrawal symptoms and appropriate transition off the study drug at completion.
Article · Nov 2010 · Journal of pain and symptom management