Oxycodone Interactions

Combining alcohol with oxycodone causes additive central nervous system and respiratory depression, dramatically increasing the risk of fatal overdose, sedation, and impaired breathing. Alcohol can also accelerate the release of oxycodone from extended-release formulations, causing dangerous spikes in blood levels.

St. John's Wort strongly induces CYP3A4, the main enzyme that metabolizes oxycodone. In a controlled crossover trial, St. John's Wort cut oral oxycodone plasma exposure (AUC) by roughly 50% and significantly reduced its analgesic effect.

Oxycodone undergoes CYP3A4-mediated metabolism to noroxycodone. A controlled crossover study in healthy volunteers showed grapefruit juice increased oxycodone AUC 1.7-fold, peak concentration 1.5-fold, and half-life 1.2-fold, while reducing formation of inactive noroxycodone, raising the risk of sedation and respiratory depression.