Opioids are widely prescribed for pain management. Many opioids are metabolized primarily by CYP450 enzymes (e.g., codeine, fentanyl, and oxycodone) or UGT enzymes (e.g., hydromorphone and morphine) (279). One study showed that oxycodone, primarily metabolized by CYP3A4, combined with ethanol (0.3 or 0.6 g/kg), resulted in a significant reduction in peak BAC compared to ethanol alone (280). However, studies of morphine and hydromorphone, both metabolized primarily by UGT, did not affect alcohol metabolism (281, 282). In another study, ethanol (BAC of 0.1%) was associated with an additional 19% decrease in respiratory rate in subjects taking oxycodone (283). A recent meta-analysis found that those who consumed alcohol achieved higher maximal concentations (Cmax) and shorter time to Cmax (Tmax) with hydromorphone compared to placebo, although this was not observed with other opioids, including morphine (266). These findings show how variable the pharmacokinetic interactions can be between opioids and ethanol depending on the drug used. However, combining any opioid with alcohol can cause severe respiratory depression and death (284). Stringent clinical precautions must be taken when prescribing opioids to patients who consume alcohol, especially given the high potential for misuse associated with opioids.
