High Doses of Oxymorphone Extended-Release Generally Well Tolerated

HONOLULU, HI—At the American Pain Society’s 31^st Annual Scientific Meeting, study investigators presented data indicating that high dosages of oxymorphone extended-release (ER) appear to be generally well tolerated in patients with chronic noncancer pain. 

Matthew Wieman, MD, and E. Gould, from Endo Pharmaceuticals, Chadds Ford, PA, completed a post hoc analysis to describe the safety profile of oxymorphone ER at dosages >180mg/day of morphine equivalents.  Pooled data from 10 clinical trials (see below for complete list of trials) consisting of 422 patients with chronic noncancer pain were analyzed to determine the frequency and type of adverse events that occurred in three different dosage categories: (1) ≥60mg to <80mg/day, (2) ≥80mg to 120mg/day, and (3) ≥120mg/day (≥180mg to<240mg/day, ≥240 to<360mg/day, and ≥360mg/day of morphine equivalents, respectively). Across all studies, 140 patients received oxymorphone ER ≥60mg to <80mg/day, 239 patients received  ≥80mg to <120mg/day, and 180 patients received ≥120mg/day.

Several common adverse events related to dose increases with opioid use (eg, constipation, nausea, vomiting, abdominal pain, depression, fatigue, sedation, somnolence, dizziness, and falls) were not evident with oxymorphone ER; small increases (<10%), no change, or small decreases were observed. The incidence of those adverse events not typically associated with opioids (eg, increased sweating, headache, pyrexia, and upper respiratory tract infection), however, was  occurred at least 3-fold more frequently with the higher oxymorphone ER dosages than with the lower dosages. High dosages of oxymorphone ER (60mg to ≥120mg/day, or 180mg to ≥360mg/day of morphine equivalents) appear to be generally well tolerated in patients with chronic noncancer pain.

Dr. Wieman added that these study results are “valid only for oxymorphone ER and should not be used to draw conclusions regarding the safety and tolerability of other opioid analgesics at high dosages.”

Summary of Clinical Trials with Patients Receiving Oxymorphone ≥60mg/day

1.     Hale ME, et al. J Pain. 2005;6(1):21-28.

2.     Sloan P, et al. Support Care Cancer. 2005;13(1):57-65.

3.     Endo Pharmaceuticals Inc. Clinical Study Report EN3202-018. A Randomized, Double-Blind, Two-Period, Crossover Trial Comparing the Safety and Effectiveness or Numorphan CR (oxymorphone controlled-release tablets) and MS Contin (morphine sulfate controlled-release tablets) for the Relief of Moderate to Severe Pain in Patients with Cancer. Chadds Ford, PA: Endo Pharmaceuticals; September 24, 2002.

4.     Gabrail NY, et al. Curr Med Res Opin. 2004;20(6)911-918.

5.     McIlwain H and Ahdieh H. Am J Ther. 2005;12(2)106-112.

6.     Slatkin NE, et al. J Opioid Manag. 2010;6(3):181-191.

7.     Endo Pharmaceuticals Inc. Clinical Study Report EN 3202-022. An Open-Label Assessment of the Long-Term Safety and Utility of Numorphan CR for the Relief of Moderate to Severe Pain in Patients with Cancer. Chadds Ford, PA: Endo Pharmaceuticals Inc; 2002.

8.     Endo Pharmaceuticals Inc. Clinical Study Report EN 3202-028. An Open-Label Effectiveness and Safety Study of Oxymorphone Extended Release in Opioid-Naïve Patients with Chronic Pain. Chadds Ford, PA: Endo Pharmaceuticals Inc; September 9, 2004.

9.     Katz N, et al. Curr Med Res Opin. 2007;23(1):117-128.

10.  Hale, ME et al. J Pain. 2007;8(2)175-184.