Impact of benzodiazepines on posaconazole serum concentrations. A population-based pharmacokinetic study on drug interaction

Abstract

In this retrospective study, analyzing blood samples from daily clinical practice of patients in various clinical settings and with different indications for antifungal therapy, concomitant medication of lorazepam was associated with decreased posaconazole concentrations. Therefore, lorazepam but not temazepam might induce posaconazole clearance by glucuronidation.

Posaconazole: An Update of Its Clinical Use

“…Patients who received a total daily dose of PCZ of 800 mg also showed a similar trend with a concentration of 292 ng/mL with PCZ and lorazepam compared to 537 ng/mL when PCZ was given alone ( p = 0.003). However, at a lower dose of 200 mg three times a day, the difference in plasma concentrations of PCZ was not statistically significant, even though the same pattern was observed (512 ng/mL versus 689 ng/mL; p = 0.186) [ 78 ]. Based on these results, the authors claimed that concomitant use of lorazepam with PCZ is associated with reduced concentrations of PCZ.…”

“…explored the concentration of PCZ at steady-state when given concomitantly with benzodiazepines in a retrospective study [ 78 ]. Blood samples were collected from patients with different indications for antifungal therapy in several clinical settings [ 78 ]. Similar plasma concentrations of PCZ were reported from patients receiving both PCZ and temazepam compared to patients who were administered PCZ alone.…”

“…However, a significant reduction in the concentration of PCZ was observed when coadministered with lorazepam compared to PCZ alone with median values of 336 ng/mL vs . 585 ng/mL, respectively ( p = 0.001) [ 78 ]. Patients who received a total daily dose of PCZ of 800 mg also showed a similar trend with a concentration of 292 ng/mL with PCZ and lorazepam compared to 537 ng/mL when PCZ was given alone ( p = 0.003).…”

“…Based on these results, the authors claimed that concomitant use of lorazepam with PCZ is associated with reduced concentrations of PCZ. They suggested that this could be due to induction of PCZ clearance by glucuronidation [ 78 ]. However, the data was not consistent with different doses of PCZ; therefore, further studies would be needed to confirm these results and determine the role of different PCZ strengths and glucuronidation in this potential drug interaction.…”

Posaconazole concentrations after allogeneic hematopoietic stem cell transplantation

“…Because of the longitudinal design of our investigation, most factors including concomitant medication might have changed over time for each patient. Analyses on the impact of these factors need not be limited to SCT recipients, but are improved by high numbers of patients enrolled (23). For some factors (e.g., diarrhea), a prospective design including very detailed documentation of clinical variables (food, bowel movement) is necessary.…”