Major
Established
Description
Concurrent use of diazepam and oxycodone dramatically increases the risk of fatal respiratory depression, per FDA boxed warning.
Mechanism
Additive CNS depression via GABA-A (diazepam) and mu-opioid receptor (oxycodone) pathways; concurrent use reduces hypoxic ventilatory response.
Clinical Significance
Patients receiving both agents show substantially higher rates of emergency department visits and overdose deaths.
Management
Avoid combination or use the lowest possible doses for the shortest duration; co-prescribe naloxone and educate patients.