Open Access Open Access  Restricted Access Subscription or Fee Access

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

Martin E. Hale, MD, Mark S. Wallace, MD, Donald R. Taylor, MD, Michael Kutch, MS, Srinivas Nalamachu, MD

Abstract


Objective: This analysis was designed to assess the pooled safety and tolerability of once-daily hydromorphone extended release (ER) (OROS® hydromorphone ER) in opioid-naïve 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-naïve 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.


Keywords


analgesics, chronic pain, hydromorphone, opioid, safety

Full Text:

PDF

References


National Center for Health Statistics: Health, United States, 2006 with Chartbook on Trends in the Health of Americans. Hyattsville, MD: National Center for Health Statistics, 2006. Available at http://www.cdc.gov/nchs/data/hus/hus06.pdf. Accessed September 23, 2011.

US Census Bureau: Current population survey, national population estimates in the United States: 1999-2002. Available at http://www.census.gov/cps/. Accessed December 7, 2011.

Chou R, Fanciullo GJ, Fine PG, et al.: Opioid treatment guidelines: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 2: 113-130.

Trescot AM, Helm S, Hansen H, et al.: Opioids in the management of chronic non-cancer pain: An update of American Society of the Interventional Pain Physicians’ (ASIPP) Guide lines. Pain Physician. 2008; 11: S5-S62.

Cone DC, Richardson LD, Todd KH, et al.: Health care disparities in emergency medicine. Acad Emerg Med. 2003; 10: 1176-1183.

Deyo RA: Pain and public policy. N Engl J Med. 2000; 342: 1211-1213.

Stewart WF, Ricci JA, Chee E, et al.: Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003; 290: 2443-2454.

Todd KH, Deaton C, D’Adamo AP, et al.: Ethnicity and analgesic practice. Ann Emerg Med. 2000; 35: 11-16.

Todd KH, Samaroo N, Hoffman JR: Ethnicity as a risk factor for inadequate emergency department analgesia. JAMA. 1993; 269: 1537-1539.

Breuer B, Pappagallo M, Tai JY, et al.: U.S. board-certified pain physician practices: Uniformity and census data of their locations. J Pain. 2007; 8: 244-250.

Argoff CE, Silvershein DI: A comparison of long- and short-acting opioids for the treatment of chronic noncancer pain: Tailoring therapy to meet patient needs. Mayo Clin Proc. 2009; 84: 602-612.

Chou R, Huffman LH: Medications for acute and chronic low back pain: A review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007; 147: 505-514.

Nicholson B: Responsible prescribing of opioids for the management of chronic pain. Drugs. 2003; 63: 17-32.

Galer BS, Coyle N, Pasternak GW, et al.: Individual variability in the response to different opioids: Report of five cases. Pain. 1992; 49: 87-91.

Pasternak GW: Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharmacol Sci. 2001; 22: 67-70.

Quang-Cantagrel ND, Wallace MS, Magnuson SK: Opioid substitution to improve the effectiveness of chronic noncancer pain control: A chart review. Anesth Analg. 2000; 90: 933-937.

Caldwell JR: Avinza–24-h sustained-release oral morphine therapy. Expert Opin Pharmacother. 2004; 5: 469-472.

Hale M, Tudor IC, Khanna S, et al.: Efficacy and tolerability of once-daily OROS hydromorphone and twice-daily extended-release oxycodone in patients with chronic, moderate to severe osteoarthritis pain: Results of a 6-week, randomized, open-label, noninferiority analysis. Clin Ther. 2007; 29: 874-888.

Mystakidou K, Clark AJ, Fischer J, et al.: Treatment of chronic pain by long-acting opioids and the effects on sleep. Pain Pract. 2011; 11: 282-289.

Rauck RL: What is the case for prescribing long-acting opioids over short-acting opioids for patients with chronic pain? A critical review. Pain Pract. 2009; 9: 468-479.

Rauck RL, Bookbinder SA, Bunker TR, et al.: A randomized, open-label, multicenter trial comparing once-a-day AVINZA (morphine sulfate extended-release capsules) versus twice-a-day OxyContin (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: improved physical functioning in the ACTION trial. J Opioid Manag. 2007; 3: 35-43.

Pergolizzi JV Jr, Taylor R Jr, Raffa RB: Extended-release formulations of tramadol in the treatment of chronic pain. Expert Opin Pharmacother. 2011; 12: 1757-1768.

Mahler DL, Forrest WH Jr: Relative analgesic potencies of morphine and hydromorphone in postoperative pain. Anesthesiology. 1975; 42: 602-607.

Quigley C, Wiffen P: A systematic review of hydromorphone in acute and chronic pain. J Pain Symptom Manage. 2003; 25: 169-178.

Kalso E, Edwards JE, Moore RA, et al.: Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain. 2004; 112: 372-380.

Bass DM, Prevo M, Waxman DS: Gastrointestinal safety of an extended-release, nondeformable, oral dosage form (OROS): A retrospective study. Drug Saf. 2002; 25: 1021-1033.

Palangio M, Northfelt DW, Portenoy RK, et al.: Dose conversion and titration with a novel, once-daily, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. J Pain Symptom Manage. 2002; 23: 355-368.

Theeuwes F: Elementary osmotic pump. J Pharm Sci. 1975; 64: 1987-1991.

Moore KT, St-Fleur D, Marricco NC, et al.: A randomized study of the effects of food on the pharmacokinetics of once-daily extended-release hydromorphone in healthy volunteers. J Clin Pharmacol. 2011; 51: 1571-1579.

Angst MS, Drover DR, Lotsch J, et al.: Pharmacodynamics of orally administered sustained-release hydromorphone in humans. Anesthesiology. 2001; 94: 63-73.

Moore KT, St-Fleur D, Marricco NC, et al.: Steady-state pharmacokinetics of extended-release hydromorphone (OROS hydromorphone): A randomized study in healthy volunteers. J Opioid Manag. 2010; 6: 351-358.

Sathyan G, Xu E, Thipphawong J, et al.: Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone. BMC Clin Pharmacol. 2007; 7: 3.

Waechter S, Eckert RR, Khanna S, et al.: Double-blind, placebo-controlled, repeat-dose assessment of once-daily OROS® hydromorphone in patients with moderate to severe chronic osteoarthritis pain. Poster presented at the 5th Congress of The European Federation of IASP Chapters (EFIC), Istanbul, Turkey, September 13-16, 2006.

Richarz U, Waechter S, Sabatowski R, et al.: Safety and efficacy of once-daily hydromorphone ER (OROS hydromorphone) compared with twice-daily oxycodone CR over 52 weeks in patients with moderate to severe chronic noncancer pain. Poster presented at the 30th Annual Scientific Meeting of the American Pain Society, Austin, Texas, May 19-21, 2011: Poster #349.

Vandenbossche J, Richarz U, Richards HM: A repeat-dose, steady-state pharmacokinetic evaluation of once-daily hydromorphone ER (OROS hydromorphone) in patients with chronic cancer or noncancer pain. Poster presented at the 30th Annual Scientific Meeting of the American Pain Society, Austin, Texas, May 19-21, 2011: Poster #337.

Binsfeld H, Szczepanski L, Waechter S, et al.: A randomized study to demonstrate noninferiority of once-daily OROS® hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain. Pain Pract. 2010; 10: 404-415.

Hale M, Khan A, Kutch M, et al.: Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. Curr Med Res Opin. 2010; 26: 1505-1518.

Hanna M, Thipphawong J: A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain. BMC Palliat Care. 2008; 7: 17.

Hanna M, Tuca A, Thipphawong J: An open-label, 1-year extension study of the long-term safety and efficacy of once-daily OROS® hydromorphone in patients with chronic cancer pain. BMC Palliat Care. 2009; 8: 14.

Wallace M, Moulin DE, Rauck RL, et al.: Long-term safety, tolerability, and efficacy of OROS hydromorphone in patients with chronic pain. J Opioid Manag. 2009; 5: 97-105.

Wallace M, Rauck RL, Moulin D, et al.: Once-daily OROS hydromorphone for the management of chronic nonmalignant pain: A dose-conversion and titration study. Int J Clin Pract. 2007; 61: 1671-1676.

Wallace M, Rauck RL, Moulin D, et al.: Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain. J Int Med Res. 2008; 36: 343-352.

Wallace M, Skowronski R, Khanna S, et al.: Efficacy and safety evaluation of once-daily OROS hydromorphone in patients with chronic low back pain: A pilot open-label study (DO-127). Curr Med Res Opin. 2007; 23: 981-989.

Wallace M, Thipphawong J: Open-label study on the long-term efficacy, safety, and impact on quality of life of OROS hydromorphone ER in patients with chronic low back pain. Pain Med. 2010; 11: 1477-1488.

Mallinckrodt Inc.: Exalgo (Hydromorphone HCl) Extended-Release Tablets CII [Package Insert]. Hazelwood, MO: Mallinckrodt Inc., 2010.

King Pharmaceuticals: Embeda (Morphine Sulfate and Naltrexone Hydrochloride) [Package Insert]. Bristol, TN: King Pharmaceuticals, 2009.

Purdue Pharma LP: OxyContin (Oxycodone Hydrochloride Controlled-Release) Tablets CII [Package Insert]. Stamford, CT: Purdue Pharma LP, 2010.

Endo Pharmaceuticals, Inc.: Opana ER (Oxymorphone Hydrochloride) Extended-Release Tablets [Package Insert]. Chadds Ford, PA: Endo Pharmaceuticals, Inc., 2008.

McNeil-Janssen Pharmaceuticals, Inc.: Duragesic (Fentanyl Transdermal System) [Package Insert]. Raritan, NJ: Ortho-McNeil-Janssen Pharmaceuticals, Inc., 2006.

Cepeda MS, Farrar JT, Baumgarten M, et al.: Side effects of opioids during short-term administration: Effect of age, gender, and race. Clin Pharmacol Ther. 2003; 74: 102-112.

Bijur PE, Esses D, Birnbaum A, et al.: Response to morphine in male and female patients: Analgesia and adverse events. Clin J Pain. 2008; 24: 192-198.

Knotkova H, Fine PG, Portenoy RK: Opioid rotation: The science and the limitations of the equianalgesic dose table. J Pain Symptom Manage. 2009; 38: 426-439.

Bruera E, Pereira J, Watanabe S, et al.: Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer. 1996; 78: 852-857.

Cone EJ, Darwin WD, Gorodetzky CW, et al.: Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. Drug Metab Dispos. 1978; 6: 488-493.

Smith HS: Opioid metabolism. Mayo Clin Proc. 2009; 84: 613-624.

Parsells Kelly J, Cook S, Kaufman D, et al.: Prevalence and characteristics of opioid use in the US adult population. Pain. 2008; 138(3): 507-513.




DOI: https://doi.org/10.5055/jom.2012.0130

Refbacks

  • There are currently no refbacks.