Opioid titration and conversion in patients receiving morphine sulfate and naltrexone hydrochloride extended release capsules.

Webster, Lynn R; Brewer, Randall; Morris, David; Cleveland, Jody M; Setnik, Beatrice

OBJECTIVE 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). PATIENTS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.