Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules.

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Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twice-daily (q12h), KADIAN (morphine sulfate extended-release) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.





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Medicine and Health Sciences




Department of Medicine

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