Wallace, M., Moulin, D.E., Rauck, R.L., Khanna, S., Tudor, I.C., Skowronski, R., & Thipphawong, J. (2009). Long-term safety, tolerability, and efficacy of OROS hydromorphone in patients with chronic pain. Journal of Opioid Management, 5(2), 97–105.
To assess the safety and efficacy of long-term repeated dosing of osmotic extended-release oral delivery system (OROS) hydromorphone used to relieve chronic pain
A patient who entered this study after completing a comparative dose-conversion study with OROS hydromorphone continued taking OROS hydromorphone at his or her stable dose. This study also included patients who had participated in a comparison of hydromorphone immediate release (IR) and OROS hydromorphone. These patients began the OROS hydromorphone study by taking 50%–100% of their established dose; dose adjustments were allowed after a minimum of two days. Dose adjustments were usually in 8 mg increments. The target duration of treatment was at least one year. Adverse events were assessed monthly, and physical exams were conducted and vital signs assessed every three months.
Multicenter open-label extension trial
BPI ratings of worst pain, least pain, and average pain were essentially stable throughout the study. Median daily dose of study medication increased from 32 mg at baseline to 40 mg at month 3 and 48 mg at months 6, 9, and 12. The most frequently reported adverse events were nausea (which 24% of patients experienced) and constipation (which 19.3% of patients experienced). The side-effect profile was similar to that of other sustained-release opioids. Most side effects usually resolved over time, although constipation was did not resolve. Laxatives can manage constipation effectively.
Authors concluded that the benefits of OROS hydromorphone were maintained when daily administration was continued. Once-daily OROS hydromorphone appeared to be safe and effective in controlling moderate to severe chronic pain.
Of patients who entered the study, 52.3% experienced a treatment-related event. (The side effects experienced by anyone who entered the study and who took at least one dose of OROS hydromorphone were reported.) Therefore, the tolerability of OROS hydromorphone, used long term, appears limited. The single dose required for pain management may be advantageous for patients who must consume multiple oral medications.