Oral Oxymorphone #181

Abstract

Background

Oxymorphone is now available in the United States as an oral analgesic in both immediate- and extended-release formulations. Previously, it has only been available in parenteral and rectal suppository form. This Fast Fact reviews oral oxymorphone and its place in pain management.

Pharmacology

Oxymorphone is a semisynthetic 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 approximately 10 times more potent than morphine, but because of its very low oral bioavailability (approximately 10%) the equianalgesic ratio of oral morphine to oral oxymorphone is only approximately 3:1 (see below).¹

Immediate-release oxymorphone has a half-life of approximately 8 hours, substantially longer than morphine (1.5 hours). Tmax (time to maximum serum concentration) however is rapid: ½ hour after oral administration.²

Extended-release oxymorphone has a half-life of approximately 10 hours and a Tmax of 2–3 hours.³

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.⁴

Drug interactions have not been well-defined for oxymorphone; it does not effect CYP2C9 or CYP3A4 pathways.⁵

Taking oxymorphone (immediate release or extended release) with food can increase serum levels by up to 50%; therefore it is recommended to be taken at least 1 hour before or 2 hours after a meal.^6,7 Note: Coingestion of alcohol with extended-release oxymorphone can raise serum levels in a seemingly unpredictable and idiopathic manner (up to 270% in some patients) and should be avoided.⁶

Clinical Studies

Oral oxymorphone has been studied most extensively in patients with chronic noncancer pain, in industry funded research. 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.

Noncancer pain: Extended-release oxymorphone has shown similar efficacy to extended-release oxycodone and superiority to placebo in randomized, blinded comparisons in patients with chronic low-back pain and osteoarthritis pain.^8–12 Immediate-release oxymorphone has been shown to be safe and effective for acute postsurgical pain.^13,14

Cancer pain: Only two controlled studies have been published.^15,16 Both involved transitioning patients with cancer from morphine or extended-release oxycodone to extended-release oxymorphone; analgesia and side effects remained stable on the extended-release oxymorphone. Uncontrolled follow-up data suggest oxymor-phone was effective and tolerated long-term.¹⁷

Dosing and Equianalgesic Conversions

Oxymorphone is not approved for use in children; no data exist on pediatric dosing. Because of its long half-life, immediate-release oxymorphone should be dosed every 6 hours. It comes as 5 and 10 mg tablets. Extended-release oxymorphone can be dosed every 12 hours and comes in 5, 10, 20, and 40 mg tablets. 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).^1,8,9,15,16

Cost (Average Wholesale Price)

Immediate-release oxymorphone 5 mg tablets are $2.40 per pill versus $0.20 per pill for 15 mg of morphine. Extended-release oxymorphone 5 mg tablets are $1.60 per pill versus $0.89 per pill for 15 mg of generic extended-release morphine versus $1.40 per pill for 10 mg of generic extended-release oxycodone.

Conclusion

Oxymorphone is a newly available oral opioid analgesic. Because of 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 are intolerant to morphine and other opioids.

Footnotes

Current version recopy edited in May 2009; web links revised.

References

Prommer

. Oxymorphone: A review. Support Care Cancer, 2006; 14:109–115.

Adams

, Ahdieh

. Single- and multiple-dose pharmacokinetic and dose-proportionality study of oxymorphone immediate-release tablets. Drugs Res Dev, 2005; 6:91–99.

Adams

, Ahdieh

. Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: Results of a randomized crossover study. Pharmacother, 2004; 24:468–476.

Lee

, Leng

, Cooper

. Measurements of plasma oxycodone, noroxycodone and oxymorphone levels in a patient with bilateral nephrectomy who is undergoing haemodialysis. Palliat Med, 2005; 19:259–260.

Adams

, Pieniazszek

, Gammaitoni

, Ahdieh

. Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways. J Clin Pharmacol, 2005; 45:337–345.

Endo Pharmaceuticals. Oxymorphone ER (Opana ER) Prescribing Information. www.endo.com/PDF/OPANA_ER_PI.pdf. 2009 October 31.

Endo Pharmaceuticals. Oxymorphone IR (Opana) Prescribing Information. www.endo.com/pdf/Opana_IR_PI.pdf. 2009 October 31.

Hale

, Ahdieh

, Ma

, Rauck

. 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.

Hale

, Dvergsten

, Gimbel

. 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.

10.

Kivitz

, Ma

, Ahdieh

, Galer

. 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.

11.

Matsumoto

, Babul

, Ahdieh

. 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.

12.

McIlwain

, Ahdieh

. 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.

13.

Gimbel

, Ahdieh

. The efficacy and safety of oral immediate-release oxymorphone for postsurgical pain. Anesth Analg, 2004; 99:1472–1477.

14.

Gimbel

, Walker

, Ma

, Ahdieh

. 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; 86:2284–2289.

15.

Gabrail

, Dvergsten

, Ahdieh

. 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.

16.

Sloan

, Slatkin

, Ahdieh

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

17.

Slatkin

, Frailey

, Ma

, Ahdieh

. 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.