Hydrocodone vs Oxycodone and Postoperative Pain and Opioid Use in Joint Arthroplasty.

CYP2D6 metabolises both hydrocodone and oxycodone to active metabolites; analysis restricted to normal metabolisers (NMs).

Preplanned secondary analysis of a randomised trial in 663 CYP2D6 normal metabolisers undergoing joint arthroplasty. Hydrocodone was associated with a lower composite pain score (9.0 vs 9.3) and, above all, substantially lower cumulative opioid exposure (93.5 vs 154.5 morphine milligram equivalents over 10 days) than oxycodone. No difference in mobility, anxiety or depression. Findings were robust in sensitivity analyses and consistent for knee but not hip arthroplasty.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The pharmacogenetic contribution here is indirect: the study compares two CYP2D6 substrates within a single (NM) metaboliser status and suggests preferring hydrocodone to limit opioid exposure. Useful for prescribing but not a CPIC-style genotype-guided dosing recommendation. The next step would be to test both opioids in non-NM metabolisers, where the genotype effect would fully apply.

Analysis by Dr Thibaut Benquey