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Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of
Saartje Verfaillie1, Laurent Godinas1, Isabel Spriet2
1Department of Respiratory Diseases, Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium.
Background:
Variability in triazole plasma concentrations by drug interactions is well known. An interaction between voriconazole and flucloxacillin has already been described. In our case we observed a similar interaction between posaconazole and flucloxacillin, which in our knowledge has not ever been reported in literature.
Case Presentation:
A 60-year-old male who had a double lung transplantation for end-stage chronic obstructive pulmonary disease was being treated with voriconazole for invasive pulmonary aspergillosis (IPA). During this treatment he presented at the emergency room and was diagnosed with endocarditis for which a combination of amoxicillin, flucloxacillin and gentamicin was initiated. A known interaction between voriconazole and flucloxacillin was observed, with a drop of the voriconazole levels, and treatment for IPA was switched to posaconazole. After ending the treatment for endocarditis, the patient had a catheter infection for which flucloxacillin was reinitiated. Unexpectedly we saw a similar immediate drop in posaconazole levels, recovering after ending treatment with flucloxacillin.
Conclusions:
We describe a new interaction between posaconazole and flucloxacillin. Presumably the underlying mechanism is activation of the pregnane X receptor by flucloxacillin, which can induce cytochrome P450, uridine glucuronosyl transferase (UGT1A4) and P-glycoprotein. We advise caution when combining flucloxacillin and triazoles, because interactions may lead to undertreatment of invasive aspergillosis.
Insights
Flucloxacillin can significantly lower posaconazole levels, potentially leading to undertreatment of invasive aspergillosis. This newly identified drug interaction warrants caution when combining these medications.
Area of Science:
- Pharmacology
- Drug Interactions
- Mycology
Background:
- Drug interactions affecting triazole plasma concentrations are well-documented.
- A known interaction exists between voriconazole and flucloxacillin.
- This study investigates a potential interaction between posaconazole and flucloxacillin.
Observation:
- A lung transplant patient on voriconazole for invasive pulmonary aspergillosis (IPA) experienced a known voriconazole-flucloxacillin interaction.
- Voriconazole was switched to posaconazole, and flucloxacillin was later reinitiated for a catheter infection.
- A similar, unexpected drop in posaconazole levels was observed upon flucloxacillin reintroduction.
Findings:
- A novel drug interaction between posaconazole and flucloxacillin is described.
- Flucloxacillin likely induces metabolic enzymes (CYP450, UGT1A4) and P-glycoprotein via pregnane X receptor activation.
- This interaction leads to significantly reduced posaconazole plasma concentrations.
Implications:
- Caution is advised when co-administering flucloxacillin with triazole antifungals like posaconazole.
- This interaction may result in sub-therapeutic drug levels, potentially leading to treatment failure for invasive aspergillosis.
- Monitoring of posaconazole levels is recommended during concurrent flucloxacillin therapy.
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