Rifampin Greatly Reduces the Plasma Concentrations of Intravenous and Oral Oxycodone

Abstract

Induction of cytochrome P450 3A by rifampin reduced the area under the oxycodone concentration-time curve of intravenous and oral oxycodone. The pharmacologic effects of oxycodone were modestly attenuated. To maintain adequate analgesia, dose adjustment of oxycodone may be necessary, when used concomitantly with rifampin.

Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone

“…This difference is plausible because, unlike midazolam, the elimination of oxycodone is not solely dependent on CYP3A enzymes as oxycodone is also metabolised by CYP2D6 [5,6]. The smaller effect of itraconazole on oral oxycodone is also explained by the higher bioavailability of oxycodone as compared to midazolam [10,14].…”

“…Voriconazole, an effective inhibitor of several CYP enzymes, profoundly delays the elimination of oxycodone [9]. On the other hand, rifampicin, a strong inducer of CYP enzymes, effectively enhances the elimination of both oral and intravenous oxycodone [10].…”

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

“…The behavioural measures were performed before and at 1, 2, 3, 4, 5, 6, 8, 10 and 12 h after oxycodone as described earlier [32]. Subjective assessment of drowsiness, deterioration of performance, self-reported drugeffect, pleasantness and nausea or vomiting was quantified using visual analog scales (VAS) and scored 0-100.…”

The Role of Opioid Analgesics in the Treatment of Pain in Cancer Patients

“…Oxycodone reduces oral bioavailability of cyclosporine by half. In healthy patients, rifampin, a CYP3A4 inducer, greatly decreased oral and IV oxycodone AUC by 86% and 53%, respectively (P < 0.001), and modestly reduced analgesia and increased plasma metabolite-to-parent compound ratios for noroxycodone and noroxymorphone (P < 0.001) (Nieminen et al, 2009). A pharmacodynamic interaction of oxycodone with other drugs acting on the central nervous system, such as benzodiazepines, neuroleptics, and antidepressants, may intensify oxycodone adverse effects, especially sedation, and respiratory depression may be intensified in the case of patients who are more sensitive to opioids.…”