Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report

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.