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Clinical applications of oxymorphone

Nalini Vadivelu, MD, Monisa Maria, MBBS, Suneil Jolly, MD, Julia Rosenbloom, MD, Arun Prasad, MD, Alan David Kaye, MD, PhD


Oxymorphone (14-hydroxydihydromorphinone), a pyridine ring unsubstituted pyridomorphinan, a semisynthetic opioid analgesic derived from thebaine, first developed in the year 1914 and has been available as oxymorphone hydrochloride parenteral forms in the United States since 1959, when the US Food and Drug Administration approved it. Over the years, it has been used for the alleviation of moderate-to-severe pain. Pharmacological considerations, new and traditional formulations, clinical indications, and recent study populations are examined in this review. Specific considerations for oxymorphone interactions are focused on as well as specific side effects and end organ considerations. Although discovered many decades ago and used as parenteral formulation, the newer oral preparations of oxymorphone (immediate release and extended release) that were approved in 2006 can provide additional options for customizing therapy to accommodate various patient needs. This newer oral formulation could make this powerful agent an important drug in the armamentarium of the healthcare provider caring for patients with pain.


oxymorphone, pain, elderly, pharmacology, thebaine

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Ercoli N, Lewis MN: Studies on analgesics; the time-action curves of morphine, codeine, dilaudid and demerol by various methods of administration; analgesic activity of acetylsalicylic acid and aminopyrine. J Pharmacol Exp Ther. 1945; 84: 301-317.

Hale ME, Ahdieh H, Ma T, et al.: Efficacy and safety of OPANA ER (oxymorphone extended release) for relief of moderate to severe chronic low back pain in opioid-experienced patients: A 12-week, randomized, double-blind, placebo-controlled study. J Pain. 2007; 8(2): 175-184.

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.

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.

Matsumoto AK, 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.

Armstrong SC, Cozza KL: Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: Theory and clinical reality, Part II. Psychosomatics. 2003; 44(6): 515-520.

Baselt RC: Disposition of toxic drugs and chemicals in man. Foster City, CA: Biomedical Publications, 2008: 2.

Sinatra R, Hyde NH, Harrison DM: Oxymorphone revisited. Semin Anesth. 1988; 7: 209-215.

O(Neil MJ: The Merck Index–An Encyclopedia of Chemicals, Drugs, and Biochemicals, 13th edn. Whitehouse Station, NJ: Merck and Co., 2001.

Poyhia R, Seppala T: Liposolubility and protein binding of oxycodone in vitro. Pharmacol Toxicol. 1994; 74(1): 23-27.

Fand I SR. Whole body autoradiographic localization of C[14] labelled morphine and nalorphine. Anat Rec. 1978; 190: 392-393.

Steinfels GF, Cook L: Antinociceptive profiles of mu and kappa opioid agonists in a rat tooth pulp stimulation procedure. J Pharmacol Exp Ther. 1986; 236(1): 111-117.

Koman A, Einarsson M, Terenius L: Agonist-antagonist properties of fluorescent opioid probes in the guinea-pig myenteric plexus-longitudinal muscle preparation. Naunyn Schmiedebergs Arch Pharmacol. 1985; 331(4): 355-358.

Ananthan S, Khare NK, Saini SK, et al.: Identification of opioid ligands possessing mixed micro agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone [correction of hydropmorphone]. J Med Chem. 2004; 47(6): 1400-1412.

Pasternak GW: Opiate, enkephalin, and endorphin analgesia: Relations to a single subpopulation of opiate receptors. Neurology. 1981; 31(10): 1311-1315.

Pasternak GW: Multiple opiate receptors: Deja vu all over again. Neuropharmacology. 2004; 47(Suppl 1): 312-323.

Leighton GE, Hill RG, Hughes J: Effects of 5-HT and alpha 1 adrenoceptor antagonists on kappa opioid-induced sedation. Pharmacol Biochem Behav. 1988; 31(4): 899-904.

Matsumoto AK: Oral extended-release oxymorphone: A new choice for chronic pain relief. Expert Opin Pharmacother. 2007; 8(10): 1515-1527.

Endo Pharmaceuticals Inc.: OPANA (oxymorphone hydrochloride)–Full prescribing information. Chadds Ford, PA: Endo Pharmaceuticals Inc, 2007.

Adams MP, 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.

Sloan PA, Barkin RL: Oxymorphone and oxymorphone extended release: A pharmacotherapeutic review. J Opioid Manag. 2008; 4(3): 131-44.

Turk DC, Cohen MJ: Sleep as a marker in the effective management of chronic osteoarthritis pain with opioid analgesics. Semin Arthritis Rheum. 2010; 39(6): 477-490.

Victor TW, Alvarez NA, Gould E: Opioid prescribing practices in chronic pain management: Guidelines do not sufficiently influence clinical practice. J Pain. 2009; 10(10): 1051-1057.

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

Mayyas F, Fayers P, Kaasa S, et al.: A systematic review of oxymorphone in the management of chronic pain. J Pain Symptom Manage. 2010; 39: 296-308.

Terman GBJ: Spinal Mechanisms and their modulation. In: Loeser JD, Butler SH, Chapman CR, et al. (eds.): Bonica’s Management of Pain, 3rd edn. Lippincott Williams & Wilkins, 2001: 73-152.

Haddox JD, Joranson DE, Angarola RT, et al.: The use of opioids for the treatment of chronic pain. A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clin J Pain. 1997; 13(1): 6-8.

Stephens J, Laskin B, Pashos C, et al.: The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors. Rheumatology (Oxford). 2003; 42(Suppl 3): iii40-52.

Austrup ML, Korean G: Analgesic agents for the postoperative period. Opioids. Surg Clin North Am. 1999; 79(2): 253-273.

Brown AK, Christo PJ, Wu CL: Strategies for postoperative pain management. Best Pract Res Clin Anaesthesiol. 2004; 18(4): 703-717.

Jain S, Datta S: Postoperative pain management. Chest Surg Clin N Am. 1997; 7(4): 773-799.

Harrison D, Sinatra RS: Oxymorphone for use in patient-controlled analgesia–The ideal PCA drug? Anesth Analg. 1987; 66: 78.

Joranson DE, Gilson AM: Controlled substances and pain management: A new focus for state medical boards. Federation Bull. 1998; 85(2): 78-83.

Centers for Disease Control and Prevention: Prevention CfDCa. Thrombotic thrombocytopenic purpura (TTP)—like illness associated with intravenous opana ER abuse — Tennessee, 2012 Atlanta, GA: Centers for Disease Control and Prevention, 2013. Available at Accessed February 2013.

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(7): 767-776.

Appleton JC: Clinical evaluation and observation of 14-hydroxydihydromorphinone (Numorphan). Anesth Analg. 1960; 39: 505-510.

Seigleman M, Wasmuth CE: The use of oxymorphone hydrochloride during anesthesia for operations on the head and neck. A preliminary report. Cleve Clin Q. 1960; 27: 157-161.

Wasmuth CE, Homi J: A review of oxymorphone hydrochloride (Numorphan) analgesia employed for general surgery, including clinical experience with five hundred and twenty-eight patients. Cleve Clin Q. 1961; 28: 262-269.

Sinatra RS, Harrison DM: A comparison of oxymorphone and fentanyl as narcotic supplements in general anesthesia. J Clin Anesth. 1989; 1(4): 253-258.

Kaufman J. Physical constants of narcotic analgesics. Drug Alcohol Depend. 1975; 1: 103-105.

Fahmy NR, Bottros MR, Charchaflieh J, et al.: A double-blind comparison of oxymorphone and fentanyl as supplements to nitrous oxide anesthesia. Anesth Analg. 1987; 66: S53.

Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000; 43(9): 1905-1915.

Krashin D, Sullivan M, Ballantyne J: What are we treating with chronic opioid therapy? Curr Rheumatol Rep. 2013; 15(3): 311.

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(2): 106-112.

Chou R, Qaseem A, Snow V, et al.: Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 147(7): 478-491.

Peniston JH, 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.

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(1): 57-65.

Beaver WT, Wallenstein SL, Houde RW, et al.: Comparisons of the analgesic effects of oral and intramuscular oxymorphone and of intramuscular oxymorphone and morphine in patients with cancer. J Clin Pharmacol. 1977; 17(4): 186-198.

Mercadante S: The use of anti-inflammatory drugs in cancer pain. Cancer Treat Rev. 2001; 27(1): 51-61.

Adams M, Pieniaszek HJ Jr, Gammaitoni AR, et al.: Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways. J Clin Pharmacol. 2005; 45(3): 337-345.

Fiske WD, Jobes J, Xiang Q, et al.: The effects of ethanol on the bioavailability of oxymorphone extended-release tablets and oxymorphone crush-resistant extended-release tablets. J Pain. 2012; 13(1): 90-99.

White JM, Irvine RJ: Mechanisms of fatal opioid overdose. Addiction. 1999; 94(7): 961-972.

Endo Pharmaceuticals Inc.: NUMORPHAN (oxymorphone hydrochloride injection and suppositories) full prescribing information. Chadds Ford, PA: Endo Pharmaceuticals Inc., 2004.

Jasinski DR: Tolerance and dependence to opiates. Acta Anaesthesiol Scand. 1997; 41(1 Pt 2): 184-186.

Liang DY, Guo T, Liao G, et al.: Chronic pain and genetic background interact and influence opioid analgesia, tolerance, and physical dependence. Pain. 2006; 121(3): 232-240.

O’Brien C: Drug addiction and drug abuse. In Hardman JG, Laurence L, Molinoff PB, et al. (eds.): Goodman and Gillman’s: The Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 1996: 559-561.

Harden RN: Chronic pain and opiates: A call for moderation. Arch Phys Med Rehabil. 2008; 89(3 Suppl 1): S72-S76.

Brena SF, Sanders SH: Opioid Use in managing non cancer pain: The cart before the horse. APS Bull. 1991; 4: 7-8.

Puttfarcken PS, Werling LL, Cox BM: Effects of chronic morphine exposure on opioid inhibition of adenylyl cyclase in 7315c cell membranes: A useful model for the study of tolerance at mu opioid receptors. Mol Pharmacol. 1988; 33(5): 520-527.

Loh HH, Tao TP, Smith AP: Invited review: Role of receptor regulation in opioid tolerance mechanisms. Synapse. 1988; 2: 457-462.

Whistler JL, Chuang HH, Chu P, et al.: Functional dissociation of mu opioid receptor signaling and endocytosis: Implications for the biology of opiate tolerance and addiction. Neuron. 1999; 23(4): 737-746.

Zuo Z: The role of opioid receptor internalization and beta-arrestins in the development of opioid tolerance. Anesth Analg. 2005; 101(3): 728-734,

Manara L, Bianchi G, Ferretti P, et al.: Inhibition of GI transit by morphine in rats results primarily from direct drug action on gut opioid investigational sites. J Pharmacol Exp Ther. 1986; 237(3): 945-949.

Inturrisi CE: Clinical pharmacology of opioids for pain. Clin J Pain. 2002; 18(4 Suppl): S3-S13.

Kurz A, Sessler DI: Opioid-induced bowel dysfunction: Pathophysiology and potential new therapies. Drugs. 2003; 63(7): 649-671.

Thomas J: Opioid-induced bowel dysfunction. J Pain Symptom Manage. 2008; 35(1): 103-113.

Chemoreceptor trigger zone, 2013. Available at Accessed February 1, 2013.

Hermens JM, Ebertz JM, Hanifin JM, et al.: Comparison of histamine release in human skin mast cells induced by morphine, fentanyl, and oxymorphone. Anesthesiology. 1985; 62(2): 124-129.

George JN: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med. 2006; 354(18): 1927-1935.

George JN, Terrell DR, Vesely SK, et al.: Thrombotic microangiopathic syndromes associated with drugs, HIV infection, hematopoietic stem cell transplantation and cancer. Presse Med. 2012; 41(3 Pt 2): e177-e188.

Pasero C, Portenoy R, McCaffery M: Opioid analgesics. In McCaffery M, Pasero C (eds.): Pain Clinical Manual. St Louis, MO: Mosby, 1999: 161-299.

Dews TE, Mekhail N: Safe use of opioids in chronic noncancer pain. Cleve Clin J Med. 2004; 71(11): 897-904.

Smith ML, Hughes RO, Levine B, et al.: Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry. J Anal Toxicol. 1995; 19(1): 18-26.

Garside D, Hargrove RL, Winecker RE: Concentration of oxymorphone in postmortem fluids and tissue. J Anal Toxicol. 2009; 33(3): 121-128.



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