Safety and tolerability of OROS® hydromorphone ER in adults with chronic noncancer and cancer pain: pooled analysis of 13 studies.

Objective: This analysis was designed to assess the pooled safety and tolerability of once-daily hydromorphone extended release (ER) (OROS® hydromorphone ER) in opioid-naive and opioid-tolerant patients with chronic cancer or noncancer pain. Design: Safety results were pooled from 13 controlled and uncontrolled clinical studies, with varying approaches to dosing and titration, pain etiology, and duration of exposure. Patients and interventions: Of the 3,075 patients in the pooled population, 2,335 (76 percent) received at least one dose of OROS hydromorphone ER, with a duration of dosing of up to 1.5 years; 420 patients were treated for at least 6 months and 141 for longer than 1 year. Main outcome measures: The primary outcome measure was the occurrence of adverse events (AEs). Descriptive statistics were used to analyze the incidence of AEs in the overall population as well as according to baseline characteristics. Results: Overall AE incidence with OROS hydromorphone ER treatment was 80.5 percent (1,880/2,335 patients). The most common treatment-related AEs were constipation (28.9 percent, 674 patients) and nausea (22.7 percent, 529 patients), and most cases were mild to moderate in severity. The incidence of overall AEs did not undergo a notable change over time. Opioid-related AEs were higher in patients ≥ 65 years of age, female patients, and opioid-naive patients. Serious adverse events (SAEs) were reported by 10.2 percent (239) of patients. A total of 64 deaths occurred, none of which were considered related to OROS hydromorphone ER treatment. Conclusions: OROS hydromorphone was generally well tolerated in short- and long-term studies and demonstrated a consistent AE profile over time.