Safety and tolerability of once-daily OROS? hydromorphone extended-release in opioid-tolerant adults with moderate-to-severe chronic cancer and noncancer pain: Pooled analysis of 11 clinical studies

摘要

Context: The efficacy and tolerability of once-daily hydromorphone extended release (ER) (OROS? hydromorphone ER, Exalgo?, Mallinckrodt Brand Pharmaceuticals, Inc., Hazelwood, MO) in patients with chronic cancer and noncancer pain have been reported in previous studies. Objectives: The objective of this analysis was to assess the pooled safety data of OROS hydromorphone ER in opioid-tolerant patients with chronic cancer and noncancer pain. Methods: Safety results were pooled from 11 clinical studies in opioid-tolerant patients: one 12-week, double-blind, placebo-controlled study; three active-controlled studies; and seven uncontrolled studies (durations of three to 52 weeks). Patients were included in this analysis if they took ≥1 dose of study medication. Descriptive statistics were used to analyze baseline and demographic characteristics, supplemental analgesic use, and incidence of adverse events (AEs). Results: In total, 1251 opioid-tolerant patients received ≥1 dose of OROS hydromorphone ER. Mean (SD) duration of exposure was 43.1 (67.8) days (range 1-396 days), and mean (SD) daily dose was 43.4 (47.1) mg. Overall, 1081 patients (86.4%) used supplemental rescue analgesics. The overall incidence of AEs was 76.9%. The most frequently reported AEs were nausea (23.2%), constipation (22.4%), vomiting (14.4%), somnolence (12.9%), and headache (12.8%). Treatment-related constipation occurred in 20.5% of patients, nausea in 16.8%, somnolence in 11.8%, vomiting in 8.2%, and headache in 7.0%. Serious adverse events occurred in 13.5% of patients, with the most frequently reported serious adverse events being dehydration, nausea, and vomiting. No treatment-related deaths occurred. Conclusion: Once-daily OROS hydromorphone ER demonstrated a safety and tolerability profile in opioid-tolerant patients that is consistent with the known safety profiles of opioids.