Hydrocodone matched oxycodone for pain, with lower opioid use after joint replacement

Clinical takeaway: For opioid-naive patients undergoing hip or knee arthroplasty as part of a multimodal pain regimen, hydrocodone may reduce postoperative opioid exposure without sacrificing pain control.

Oxycodone is commonly viewed as the more potent postoperative opioid and is often chosen with the expectation that it provides better pain relief than hydrocodone. A new multicenter study challenges that assumption, finding no clinically meaningful pain advantage with oxycodone despite substantially greater opioid use.

Researchers analyzed 663 CYP2D6 normal metabolizers undergoing elective hip or knee arthroplasty who received either hydrocodone or oxycodone as part of multimodal postoperative pain management. Hydrocodone recipients had slightly lower composite pain scores ten days after surgery, although the authors noted the absolute difference was small and unlikely to be clinically meaningful. More importantly, patients receiving hydrocodone used about 40% less opioid overall than those receiving oxycodone.

Mobility at ten days and anxiety and depression scores at thirty days were similar between groups. The findings remained consistent across multiple sensitivity analyses. In subgroup analyses, the differences were statistically significant among patients undergoing knee arthroplasty but not among those undergoing hip arthroplasty.

The study adds comparative effectiveness evidence for two of the most commonly prescribed postoperative opioids. If similar pain relief can be achieved with substantially lower opioid exposure, hydrocodone may represent a reasonable first choice for many patients recovering from joint replacement. Because the study included only CYP2D6 normal metabolizers, the findings may not apply to patients with reduced CYP2D6 activity, including those taking strong CYP2D6 inhibitors.

"Our findings have practical implications for postoperative pain management, especially in the context of personalized medicine and opioid-sparing strategies," the study authors wrote. "For patients who are CYP2D6 normal metabolizers, a multimodal approach with hydrocodone appears to be a safe and effective option for managing acute post-total joint arthroplasty pain."

Source: Nahid NA, et al. (2026 Jul 14) JAMA Netw Open. Hydrocodone vs oxycodone and postoperative pain and opioid use in joint arthroplasty