Introduction: Opioid analgesics should not be taken concurrently with alcohol because of the potential for additive pharmacodynamic effects. With extended-release (ER) opioids there is also the potential for alcohol to cause degradation of the ER formulation leading to dose dumping. In vitro, ethanol does not cause dose dumping of oxymorphone from its ER tablet. This study evaluated the possible interaction of alcohol with ER 40-mg tablets in vivo.

Methods: Healthy adults with a history of moderate alcohol consumption participated in an open-label, randomized, 4-way crossover study. Subjects received a single oxymorphone ER 40-mg tablet with each of 4 aqueous solutions containing ethanol (40%, 20%, or 4%) or water administered in random order over 4 periods, each separated by ≥7 days. Naltrexone (50 mg) was administered to minimize the potential for opioid-induced adverse events (AEs). Oxymorphone plasma concentrations and pharmacokinetics were determined from blood samples collected periodically over 48 hours postadministration. AEs were recorded. Subjects provided informed consent and Institutional Review Board approval was obtained.

Results: Thirty subjects were enrolled in the study, and 25 received all 4 treatments. The geometric mean ratios of peak plasma concentrations (C_max) of oxymorphone increased 70%, 31%, and 7% for the 40%, 20%, and 4% ethanol solutions, respectively, relative to water. No significant effects on area under the curve (AUC) or other pharmacokinetic parameters were reported. There were no serious or unexpected AEs.

Conclusions: Coadministration of oxymorphone ER 40 mg tablets with ethanol produced a significant dose-proportional increase in oxymorphone C_max but not in AUC. Similar results were reported when oxymorphone ER was administered with food, suggesting a possible common mechanism (eg, gastric emptying, increased splanchnic blood flow) for increases in C_max. In vitro studies suggest the mechanism is unrelated to deterioration of the oxymorphone ER formulation.