Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report - PubMed (original) (raw)

Case Reports

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

Saartje Verfaillie et al. BMC Pulm Med. 2022.

Abstract

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.

Keywords: Azole; Case report; Flucloxacillin; Lung transplantation; Posaconazole.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Evolution in time of cyclosporine concentrations, dose, voriconazole and posaconazole concentrations. Legend: Evolution in time (x-axis, days) of cyclosporine concentrations vs cyclosporine dose (y-axis, primary axis), voriconazole and posaconazole concentrations (y-axis, secondary axis). During phase I and III the patient was treated with flucloxacillin

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References

1. Yi WM, Schoeppler KE, Jaeger J, Mueller SW, MacLaren R, Fish DN, et al. Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study. Ann Clin Microbiol Antimicrob. 2017;16(1):1–14. doi: 10.1186/s12941-017-0235-8. - DOI - PMC - PubMed
1. Maertens JA, Rahav G, Lee D-G, Ponce-de-León A, Ramírez Sánchez IC, Klimko N, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021;397(10273):499–509. doi: 10.1016/S0140-6736(21)00219-1. - DOI - PubMed
1. Samanta P, Clancy CJ, Marini RV, Rivosecchi RM, McCreary EK, Shields RK, et al. Isavuconazole is as effective as and better tolerated than voriconazole for antifungal prophylaxis in lung transplant recipients. Clin Infect Dis. 2021;73(3):416–26. doi: 10.1093/cid/ciaa652. - DOI - PMC - PubMed
1. Klatt ME, Eschenauer GA. Review of pharmacologic considerations in the use of azole antifungals in lung transplant recipients. J Fungi. 2021;7(2):1–16. doi: 10.3390/jof7020076. - DOI - PMC - PubMed
1. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, et al. Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil) Drug Metab Dispos. 2004;32(2):267–71. doi: 10.1124/dmd.32.2.267. - DOI - PubMed

Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report - PubMed (original) (raw)