Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

• Main Authors: Hale ME, Nalamachu SR, Khan A, Kutch M
• Format: Article
• Language: English
• Published: Dove Medical Press 2013-05-01
• Series: Journal of Pain Research
• Online Access: http://www.dovepress.com/effectiveness-and-gastrointestinal-tolerability-during-conversion-and--a12928

Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland&ndash;Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results: Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was -0.6 (0.1), and mean change (SEM) in the Roland&ndash;Morris Disability Questionnaire was -2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a &ge;30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion: The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of OROS hydromorphone ER within 2 to 4 weeks. Keywords: chronic low back pain, noncancer pain, extended-release opioids, OROS hydromorphone ER, opioid rotation, conversion and titration