Multicenter, Open-label, Prospective Evaluation of the Conversion from Previous Opioid Analgesics to Extended-release Hydromorphone Hydrochloride Administered Every 24 Hours to Patients with Persistent Moderate to Severe Pain

Background: Hydromorphone hydrochloride is a mu-opioid agonist with dose-dependent analgesic properties. Extended-release hydromorphone hydrochloride (ER hydromorphone HCl) capsules have been developed for administration every 24 hours.

Objectives: This prospective evaluation focused on the first (ie, conversion) phase of 2 identically designed, randomized, controlled studies that compared the safety and efficacy of once-daily ER hydromorphone HCl capsules with immediate-release hydromorphone hydrochloride (IR hydromorphone HCl) tablets administered 4 times daily in the treatment of persistent moderate to severe cancer- and noncancer-related pain.

Methods: Patients being treated with opioid analgesics for persistent moderate to severe pain were converted to ER hydromorphone HCl using an 8:1 conversion ratio. The dose was titrated to attain an average pain intensity (API) score < or = 4 on a 0- to 10-point numeric rating scale. Supplemental oral IR hydromorphone HCl tablets were used as rescue medication at a dose of one eighth to one sixth of the daily ER hydromorphone HCl dose.

Results: A total of 343 patients (272 [79%] with cancer pain; mean age, 57.8 years) were enrolled and converted to ER hydromorphone HCl from their previous opioids. About half (51%) were women. At baseline, the mean (SD) API score was 5.3 (2.1). Mean (SD) API scores were 4.7 (2.0) after the first 48 hours and 3.4 (2.1) by the end of titration. After 4 to 21 days of titration, 239 (70%) patients reached stabilization defined as a > or = 48-hour period with an API score of < or =4, unchanged ER hydromorphone HCl dose, and < or = 2 rescue doses per day. The stabilized patients had mean (SD) API scores of 2.7 (1.1) at the end of titration. At stabilization, 102 (43%) of 239 patients remained at their initial conversion dose, 129 (54%) had a dose increase, and 8 (3%) had a dose decrease. Frequent (> or =10% of patients) adverse events that occurred within the first 48 hours after conversion and during the entire titration phase were nausea, somnolence, headache, constipation, vomiting, and dizziness.

Conclusion: In this prospective evaluation of the conversion and titration phase of 2 randomized, controlled studies, a conversion ratio of 8:1 mg of oral morphine to oral ER hydromorphone HCl was found to be clinically useful in patients with persistent moderate to severe cancer-related or noncancer-related pain.