An open-label pharmacokinetic study of oxymorphone extended release in the presence of naltrexone in the older adult

Joseph V. Pergolizzi Jr, MD; Robert B. Raffa, PhD; Robert Taylor Jr, PhD; Swati Nagar, PhD; Sumedha Labhsetwar, MD; Nicholas Sinclair, MD; Errol M. Gould, PhD

doi:10.5055/jom.2012.0138

Authors

Joseph V. Pergolizzi Jr, MD
Robert B. Raffa, PhD
Robert Taylor Jr, PhD
Swati Nagar, PhD
Sumedha Labhsetwar, MD
Nicholas Sinclair, MD
Errol M. Gould, PhD

DOI:

https://doi.org/10.5055/jom.2012.0138

Abstract

Objective: The aging population generally has greater need for analgesics and is best served by having as many good therapeutic options as possible. Geriatric analgesia requires special consideration of age-associated physiologic changes that can affect drug dosing. The study of extended-release (ER) oxymorphone in older (=65 years of age) versus younger (18-40 years of age) male and female volunteers was described.
Methods: In this multiple-dose, parallel-group, open-label trial, healthy volunteers received a single oral dose of 20 mg oxymorphone ER on day 1, followed by a 48-hour washout period, then two oral doses of 20 mg oxymorphone ER tablets every 12 hours from day 3 to day 8, and a single oral dose of 20 mg oxymorphone ER on day 9. Naltrexone was administered each day to the subjects.
Results: The elderly had significantly higher plasma levels of oxymorphone, 6-OH-oxymorphone, and oxymorphone-3-glucuronide than the younger group (1.36-fold higher area under the concentration versus time curve [AUC] and 1.45-fold higher Cmax) when they were treated with a single dose (20 mg) of oxymorphone. Steady-state AUC and Cmax also were higher in the older group. Following adjustment for body weight, AUC values for oxymorphone and its metabolites were about 40 percent higher and the mean Cmax values were 30-35 percent higher in the older group compared to the younger group.
Conclusion: The results of the current study of an ER formulation revealed no pharmacokinetic features that would preclude dosing in the elderly. As with any drug and any age group (but particularly the elderly), oxymorphone ER should be initiated at lower doses in elderly compared to younger patients and titrated to optimal level.
Keywords: oxymorphone, elderly, pharmacokinetics, extended release
DOI:10.5055/jom.2012.0138

References

Administration on Aging: A profile of older Americans 2007. Available at http://www.agingcarefl.org/aging/AOA-2007profile.pdf. Accessed July 1, 2010.

American Geriatrics Society: Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009; 57:

-1346.

Pergolizzi J, Boger R, Budd K, et al.: Opioids and the management of chronic severe pain in the elderly: Consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008; 8(4): 287-313.

Pergolizzi J, Raffa R, Gould E: Considerations on the use of oxymorphone in geriatric patients. Expert Opin Drug Saf. 2009;

(5): 603-613.

Fine P: Pharmacological management of persistent pain in older patients. Clin J Pain. 2004; 20(4): 220-226.

Raffa R: Pharmacology of oral combination analgesics: rational therapy for pain. J Clin Pharm Ther. 2001; 26: 257-264.

Kaiko R: Pharmacokinetics and pharmacodynamics of controlled-release opioids. Acta Anaesthesiol Scand. 1997; 41: 166-174.

Chau D, Walker V, Pai L, et al.: Opiates and elderly: Use and side effects. Clin Interv Aging. 2008; 3(2): 273-278.

Arnstein P: Balancing analgesic efficacy with safety concerns in the older patient. Pain Manag Nurs. 2010; 11(2): S11-S22.

Prommer E: Oxymorphone: A review. Support Care Cancer. 2006; 14(2): 109-115.

Peniston J, Xiang Q, Gould E: Factors affecting acceptability of titrated oxymorphone extended release in chronic low back

pain-an individual patient analysis. Curr Med Res Opin. 2010; 26(8): 1861-1871.

Ahdieh H, Ma T, Babul N, et al.: Efficacy of oxymorphone extended release in postsurgical pain: A randomized clinical trial in knee arthroplasty. J Clin Pharmacol. 2004; 44: 767-776.

McIlwain H, Ahdieh H: Safety, tolerability, and effectiveness of oxymorphone extended release for moderate to severe osteoarthritis pain: A one year study. Am J Ther. 2005; 12: 106-112.

Kivitz A, Ma C, Ahdieh H, et al.: A 2-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase III trial comparing the efficacy of oxymorphone extended release and placebo in adults with pain associated with osteoarthritis of the hip or knee. Clin Ther. 2006; 28(3): 352-364.

Sloan P, Slatkin N, Ahdieh H: Effectiveness and safety of oral extended-release oxymorphone for the treatment of cancer pain: A pilot study. Support Care Cancer. 2005; 13: 57-65.

Hale M, Dvergsten C, Gimbel J: Efficacy and safety of oxymorphone extended release in chronic low back pain: Results of a randomized, double-blind, placebo- and active-controlled phase III study. J Pain. 2005; 6(1): 21-28.

Matsumoto A, Babul N, Ahdieh H: Oxymorphone extended release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: Results of a randomized, double-blind, placebo- and active-controlled phase III trial. Pain Med. 2005; 6(5): 357-366.

Hale M, Ahdieh H, Ma T, et al.: Efficacy and safety of Opana ER (oxymorphone extended release) in opioid-experienced patients: A 12-week, randomized, double-blind, placebocontrolled study. J Pain. 2007; 8(2): 175-184.

Aqua K, Gimbel J, Singla N, et al.: Efficacy and tolerability of oxymorphone immediate release for acute postoperative pain after abdominal surgery: A randomized, double-blind, activeand placebo-controlled, parallel-group trial. Clin Ther. 2007; 29(6): 1000-1012.

Rauck R, Ma T, Kerwin R, et al.: Titration with oxymorphone extended release to achieve effective long-term pain relief and improve tolerability in opioid-naive patients with moderate to severe pain. Pain Med. 2008; 9(7): 777-785.

Peniston J, Gould E: Oxymorphone extended release for the treatment of chronic low back pain: A retrospective pooled analysis of enriched-enrollment clinical trial data stratified according to age, sex, and prior opioid use. Clin Ther. 2009; 31(2): 347-359.

Gould E, Jensen M, Victor T, et al.: The pain quality response profile of oxymorphone extended release in the treatment of low back pain. Clin J Pain. 2009; 25: 116-122.

Katz N, Rauck R, Ahdieh H, et al.: A 12-week, randomized, placebo-controlled trial assessing the safety and efficacy of oxymorphone extended release for opioid-naive patients with chronic low back pain. Curr Med Res Opin. 2007; 23(1): 117-128.

Matsumoto A: Oral extended-release oxymorphone: A new choice for chronic pain relief. Expert Opin Pharmacother. 2007;

(10): 1515-1527.

Adams M, Ahdieh H: Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: Results of a randomized crossover study. Pharmacotherapy. 2004; 24(4): 468-476.

Armstrong S, Cozza K: Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: Theory and clinical reality, Part I. Psychosomatics. 2003; 44: 167-171.

Opana (oxymorphone hydrochloride) [package-insert]. Chadds Ford, PA: Endo Pharmaceuticals, 2006.

Adams M, Pieniaszek H, Gammaitoni A, et al.: Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways. J Clin Pharmacol. 2005; 45: 337-345.

Chamberlin K, Cottle M, Neville R, et al.: Oral oxymorphone for pain management. Ann Pharmacother. 2007; 41: 1144-1152.

The Medical Letters Inc.: Oral oxymorphone (Opana). Med Lett Drugs Ther. 2007; 49(1251): 3-5.

Gibson S, Farrel M: A review of age differences in the neurophysiology of nociception and the perceptual experience of

pain. Clin J Pain. 2004; 20(4): 227-239.

Adams MP, Ahdieh H: Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets. Drugs R D. 2005; 6(2): 91-99.

Benedek IH, Jobes J, Xiang Q, et al.: Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone extended release. Drug Des Devel Ther. 2011; 5: 455-463.

Food and Drug Administration: Draft Guidance on Oxymorphone Hydrochloride. 2010.