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.

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.