Factors affecting dosing regimens of morphine sulfate extended-release (KADIAN) capsules

Arnold J. Weil, MD; Bruce Nicholson, MD; John Sasaki, MD

doi:10.5055/jom.2009.0005

Authors

Arnold J. Weil, MD
Bruce Nicholson, MD
John Sasaki, MD

DOI:

https://doi.org/10.5055/jom.2009.0005

Keywords:

KADIAN, morphine, opioid, extendedrelease opioid, pain, chronic pain, long-acting opioid

Abstract

Although most extended-release morphine formulations are indicated for use once-daily (q24h) or twicedaily (q12h), KADIAN® (morphine sulfate extendedrelease) capsules, which contain polymer-coated, extended-release morphine sulfate pellets, are indicated for q24h and q12h dosing. This analysis identified factors that might impact decisions to choose q24h or q12h regimens for patients with chronic, nonmalignant pain. Data were obtained from a supplemental analysis of the KRONUS-MSP trial, a community-based, open-label, 4-week study in which patients with chronic, nonmalignant pain (N = 1,428) were randomized to KADIAN q24h dosed either AM or PM. At week 2, investigators could switch to q12h dosing if indicated. For this analysis, demographics, baseline pain features, efficacy outcomes (changes in pain intensity, sleep interference, quality of life [SF-36v2 Health Survey], and Patient and Clinician Global Assessments of Therapy) were compared between patients who remained on q24h regimens and those who switched to q12h. By week 4 (n = 1,042), 56.8 percent of patients reporting were on q24h dosing, and 43.2 percent were dosing q12h. Older patients remained on q24h regimens more frequently than did younger patients. There were no differences in dosing regimen based on sex or race. Mean daily KADIAN doses and baseline pain scores were lower in patients who remained on q24h compared with those who switched to q12h. Patients who switched to q12h had higher pain scores at baseline and week 2 compared with patients who remained on q24h dosing. They demonstrated a smaller degree of change on the other efficacy outcomes than those who remained on q24h dosing at the week 2 visit. However, once switched to q12h, improvements in efficacy measures at week 4 were comparable between the two schedules; Patient and Clinician Global Assessments of Therapy scores also increased compared with previous therapy. Results were significant versus baseline for all outcomes. Adverse event rates were similar for the two groups; the most common adverse events were constipation and nausea. Results demonstrate that KADIAN was effective in relieving pain and improving sleep and quality-of-life scores, regardless of whether patients dosed q24h or q12h, and that dosing decisions can be made, based on individual factors, within the first few weeks of therapy.

Author Biographies

Arnold J. Weil, MD

Non-Surgical Orthopaedics, PC, Atlanta, Georgia.

Bruce Nicholson, MD

Lehigh Valley Hospital and Health Network, Allentown, Pennsylvania.

John Sasaki, MD

Casa Colina Centers for Rehabilitation, Upland, California.

References

American Pain Society: Pain Control in the Primary Care Setting. Glenview, Ill: American Pain Society, 2006.

Nagda J, Bajwa ZH: Definitions and classification of pain. In Warfield CA, Bajwa ZH (eds.): Principles and Practice of Pain Medicine. New York, NY: McGraw-Hill, 2004.

American Chronic Pain Association: Partners for understanding pain. Pain fact sheet. Available at www.theacpa.org/documents/Proclamations%20Process%20Guide%20Tool%20kit6.pdf. Accessed December 12, 2007.

Roper Starch Worldwide Inc: Chronic pain in America: Roadblocks to relief. 1999. Available at www.ampainsoc.org/whatsnew/summary1_road.htm. Accessed May 30, 2006.

Andersson HI: The course of non-malignant chronic pain: A 12-year follow-up of a cohort from the general population. Eur J Pain. 2004; 8(1): 47-53.

Smith BH, Elliott AM, Chambers WA, et al.: The impact of chronic pain in the community. Fam Pract. 2001; 18(3): 292-299.

Nicholson B: Responsible prescribing of opioids for the management of chronic pain. Drugs. 2003; 63(1): 17-32.

Marcus DA: Treatment of nonmalignant chronic pain. Am Fam Physician. 2000; 61(5): 1331-1338, 1345-1346.

World Health Organization: Cancer pain relief and palliative care: Report of a WHO expert committee [World Health Organization Technical Report Series, 804]. Geneva, Switzerland: World Health Organization, 1990.

Supernaw RB: Pain management: important principles in the drug management of pain. Hospital Physician. August 2002; 45-52.

Gutstein HB, Akil H: Opioid analgesics. In Hardman JG, Limbird LE, Gilman AG (eds.): Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 10th ed. New York, NY: McGraw-Hill, 2001.

Adams D, Gunyea I, Bhakta B, et al.: Retrospective assessment of frequency of dosing of sustained release opiate preparations in chronic pain patients [abstract]. Pain Med. 2002; 3: 185.

McCarberg BH, Barkin RL: Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Am J Ther. 2001; 8(3): 181-186.

Lipman AG, Jackson KC II: Opioid pharmacotherapy. In Warfield CA, Bajwa ZH (eds.): Principles and Practices of Pain Medicine. New York: McGraw-Hill, 2004.

Broomhead A, Kerr R, Tester W, et al.: Comparison of a once-a-day sustained-release morphine formulation with standard oral morphine treatment for cancer pain. J Pain Symptom Manage. 1997; 14(2): 63-73.

Dickinson BD, Altman RD, Nielsen NH, et al.: Use of opioids to treat chronic, noncancer pain. West J Med. 2000; 172(2): 107-115.

MS Contin [package insert]. Stamford, CT: Purdue Pharma L.P., 2007.

AVINZA [package insert]. Bristol, TN: King Pharmaceuticals, Inc, 2006.

KADIAN [package insert]. Piscataway, NJ: Alpharma Pharmaceuticals LLC, 2007.

Kerr RO, Tester WJ: A patient preference study comparing two extended-release morphine sulfate formulations (oncedaily KADIAN® versus twice-daily MS Contin®) for cancer pain. Clin Drug Invest. 2000; 19(1): 25-32.

Royal M: A head-to-head, single-dose trial of KADIAN® vs AVINZA® 30 mg in healthy, opioid-naïve subjects in the fed state: comparison of pharmacokinetics [abstract]. Abstract 732. J Pain. 2005; 6(3): S41.

Nicholson B, Ross E, Weil A, et al.: Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules. Curr Med Res Opin. 2006; 22(3): 539-550.

International Conference on Harmonisation: Guidance for Industry. Good Clinical Practice: Consolidated Guidance (ICHE6). Rockville, MD: Center for Drug Evaluation & Research (CDER), 1996.

US Food and Drug Administration: Code of Federal Regulations, Title 21. US Food and Drug Administration, 2004.

World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Edinburgh: Scotland, 2000.

Farrar JT, Young JP Jr, LaMoreaux L, et al.: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001; 94(2): 149-158.

Ware JE Jr, Kosinski M, Dewey JE: How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: QualityMetric Incorporated, 2000.

AGS Panel on Persistent Pain in Older Persons: The management of persistent pain in older persons. J Am Geriatr Soc. 2002; 50(6 suppl): S205-S224.

Owen JA, Sitar DS, Berger L, et al.: Age-related morphine kinetics. Clin Pharmacol Ther. 1983; 34(3): 364-368.

Vuyk J: Pharmacodynamics in the elderly. Best Pract Res Clin Anaesthesiol. 2003; 17(2): 207-218.

Claxton AJ, Cramer J, Pierce C: A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001; 23(8): 1296-1310.

Ackerman SJ, Mordin M, Reblando J, et al.: Patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride controlled-release among patients with chronic nonmalignant pain. J Manag Care Pharm. 2003; 9(3): 223-231.

Rauck RL, Bookbinder SA, Bunker TR, et al.: The ACTION study: a randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA®) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin®) for the treatment of chronic, moderate to severe low back pain. J Opioid Manag. 2006; 2(3): 155-166.

Rauck RL, Bookbinder SA, Bunker TR, et al.: A randomized, open-label study of once-a-day AVINZA® (morphine sulfate extended-release capsules) versus twice-a-day OxyContin® (oxycodone hydrochloride controlled-release tablets) for chronic low back pain: The extension phase of the ACTION trial. J Opioid Manag. 2006; 2(6): 325-328, 331-333.

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-aday 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(1): 35-43.

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(5): 874-888.