Background     Oxymorphone is an old synthetic opioid, which has been available in the U.S. as an oral analgesic in both immediate- and extended-release formulations since 2006. This Fast Fact will review oral oxymorphone and its place in pain management.

Pharmacology 

• Oxymorphone is a semi-synthetic mu-opioid receptor agonist; it has some delta-opioid receptor agonism but little activity at the kappa receptor.
• Oxymorphone is highly lipophilic.  Parenterally it is about 10 times more potent than morphine, but – due to its very low oral bioavailability (~10%) – the equianalgesic ratio of oral morphine to oral oxymorphone is only ~3:1 (see below) (15). 
• Oxymorphone IR has a half-life of ~8 hours, substantially longer than morphine (1.5 hours).  Tmax (time to maximum serum concentration) however is rapid:  ½ hour after oral administration (2).
• Oxymorphone ER has a half-life of ~10 hours and a Tmax of 2-3 hours (1).
• Oxymorphone is metabolized in the liver to 6-hydroxyoxymorphone (likely active) and oxymorphone-3-glucuronide (unknown if active).  Both oxymorphone and its metabolites accumulate in renal failure; oxymorphone is removed during hemodialysis (12). 
• Drug interactions have not been well-defined for oxymorphone; it does not effect CYP2C9 or CYP3A4 pathways (3). 
• Taking oxymorphone IR or ER with food can increase serum levels by up to 50%; therefore it is recommended to be taken at least one hour before or two hours after a meal (4,5).  Note: Co-ingestion of alcohol with oxymorphone ER can raise serum levels in a seemingly unpredictable and idiopathic manner (up to 270% in some patients) and should be avoided (4).

Clinical Studies    Oral oxymorphone has been studied most extensively in patients with chronic non-cancer pain, in industry-funded research completed in the mid-2000s.  No head-to-head comparisons with morphine have been undertaken.  All studies suggest oxymorphone’s side effects are similar in frequency and magnitude to other oral opioids.

• Non-cancer pain.  Oxymorphone ER has shown similar efficacy to oxycodone ER and superiority to placebo in randomized, blinded comparisons in patients with chronic low-back pain and osteoarthritis pain (9-11,13-14). Oxymorphone IR has been shown to be safe and effective for acute post-surgical pain (7,8).
• Cancer pain.  Only two controlled studies have been published (6,17).  Both involved transitioning cancer patients from morphine or oxycodone ER to oxymorphone ER; analgesia and side effects remained stable on the oxymorphone ER.  Uncontrolled follow-up data suggest oxymorphone was effective and tolerated long-term (16,18).

Dosing & Equianalgesic Conversions    Oxymorphone is not approved for use in children; no data exist on pediatric dosing.  Due to its long half-life, oxymorphone IR should be dosed every 6 hours.  It comes as 5 and 10 mg tabs. Oxymorphone ER can be dosed q12 hours and comes in 5, 10, 20, and 40 mg tabs.  Equianalgesic conversion data range from: 1.2-2:1 for oral oxycodone:oral oxymorphone and 1.8-3:1 for oral morphine:oral oxymorphone (i.e. 18-30 mg oral morphine = 10 mg oxymorphone) (6,9,10,15,17). 

Cost    Oxymorphone is more expensive than many other commonly used oral opioids. One hundred 5 mg immediate-release tablets costs approximately $225 USD; sixty 10 mg tablets extended-release tablets costs approximately $170 USD (September 2015, www.drugs.com).

Conclusion     Despite some unique pharmacologic features, there are no clinical data to suggest oxymorphone is more effective or better tolerated than other oral opioids.  Due to its increased cost, restrictions on taking it with food, and lack of evidence for superior efficacy, it is most appropriate for use in patients who have refractory intolerance to other more commonly used oral opioids.

References

1. Adams MP, Ahdieh H.  Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites:  results of a randomized crossover study.  Pharmacother. 2004; 24:468-476.
2. Adams MP and Ahdieh H.  Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets.  Drugs Res Dev. 2005; 6:91-99.
3. Adams MP, Pieniazszek HF, Gammaitoni AR, Ahdieh H.  Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways.  J Clin Pharmacol. 2005; 45:337-345.
4. Endo Pharmaceuticals.  Oxymorphone ER (Opana ER) Prescribing Information. Available at http://www.endo.com/File%20Library/Products/Prescribing%20Information/OpanaER_prescribing_information_newformulation.html. Accessed September 2015.
5. Endo Pharmaceuticals.  Oxymorphone IR (Opana) Prescribing Information.  Available at http://www.endo.com/File%20Library/Products/Prescribing%20Information/OPANA_prescribing_information.html. Accessed September 2015.
6. Gabrail NY, Dvergsten C, Ahdieh H.  Establishing the dosage equivalency of oxymorphone extended release and oxycodone controlled release in patients with cancer pain:  a randomized controlled study.  Curr Med Res Opin. 2004; 20:911-918.
7. Gimbel JS and Ahdieh H.  The efficacy and safety of oral immediate-release oxymorphone for postsurgical pain.  Anesth Analg. 2004; 99:1472-1477.
8. Gimbel JS, Walker D, Ma T, Ahdieh H.  Efficacy and safety of oxymorphone immediate release for the treatment of mild to moderate pain after ambulatory orthopedic surgery:  results of a randomized, double-blind, placebo-controlled trial.  Arch Phys Med Rehab. 2005; 86:2284-9.
9. Hale ME, Ahdieh H, Ma T, Rauck R.  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; 8:175-184.
10. Hale ME, 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; 6:21-28.
11. Kivitz A, Ma C, Ahdieh H, Galer BS.  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; 28:352-364.
12. Lee MA, Leng MF, Cooper RM.  Measurements of plasma oxycodone, noroxycodone and oxymorphone levels in a  patient with bilateral nephrectomy who is undergoing haemodialysis.  Palliat Med. 2005; 19:259-260.
13. Matsumoto AK. Babul N, Ahdieh H.  Oxymorphone extended-release tablets relieve moderate to severe pain and improve physicial function in osteoarthritis:  results of a randomized, double-blind, placebo- and active-controlled phase III trial.  Pain Med. 2005: 6;357-366.
14. McIlwain H and Ahdieh H.  Safety, tolerability, and effectiveness of oxymorphone extended release for moderate to severe osteoarthritis pain.  A one-year study.  Am J Therap. 2005; 12:106-112.
15. Prommer E.  Oxymorphone: a review.  Support Care Cancer. 2006; 14:109-115.
16. Slatkin N, Frailey A, Ma T, Ahdieh H.  Oxymorphone extended-release offers long-term safety, effectiveness, and dose stabilization in cancer pain:  results from a one-year interim report (Abstract).  J Pain. 2003; 4(Suppl 1):84.  
17. 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.

18.Slatkin NE, Rhiner MI, Gould EM, Ma T. Ahdieh H. Long-term tolerability and effectiveness of oxymorphone extended release in patients with cancer. J Opioid Manage. 2010; 6:181-91.

Version History:  First published in May 2009; In August 2015 it was re-copy-edited by Drew Rosielle MD — web-links revised.