Importance of cytochrome 3A4 and 2D6-mediated drug–drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug–drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of “high oxycodone” [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39–16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02–1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of “high oxycodone” (OR* 0.38, 95% CI 0.18–0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.