The Effects of Ethanol on the Bioavailability of Oxymorphone Extended-Release Tablets and Oxymorphone Crush-Resistant Extended-Release Tablets

Abstract

Adverse events may occur with an extended-release (ER) opioid if tampering or coadministration with ethanol causes excessive exposure (dose dumping) to the opioid. The effects of ethanol on the in vitro dissolution and in vivo pharmacokinetics of oxymorphone ER and oxymorphone crush-resistant formulation (CRF) were evaluated. In vitro dissolution rates were measured for oxymorphone ER 40-mg and oxymorphone CRF 40-mg tablets in aqueous solutions of 0 to 40% ethanol. In 2 in vivo, open-label, randomized, crossover studies, fasted healthy volunteers received single oral doses of oxymorphone ER 40 mg or oxymorphone CRF 40 mg with 240 mL of 0 to 40% ethanol. Naltrexone was used to minimize opioid effects. In the in vitro analyses, dissolution rates of oxymorphone ER and CRF were unaffected in aqueous solutions of ≤40% ethanol. Coadministration of oxymorphone ER or oxymorphone CRF with ethanol 20 and 40% increased oxymorphone peak plasma concentrations (C max) by 14 to 80% and reduced time to C max. For both formulations, oxymorphone area under the curve and terminal half-life were largely unaffected, but C max increased with ethanol dose. Neither oxymorphone formulation exhibited dose dumping in terms of overall exposure when coingested with ethanol. Perspective Administering oxymorphone ER or oxymorphone CRF with 240 mL of ≤40% ethanol increased oxymorphone C max without dose dumping in terms of area under the curve. These results provide reassurance about the integrity of oxymorphone ER formulations with ethanol. Nonetheless, alcohol and opioids should never be combined because of the risk of respiratory depression.