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Coadministration of posaconazole and sirolimus in allogeneic hematopoietic stem cell transplant recipients

Bone Marrow Transplantation volume 51, pages 1022–1024 (2016)Cite this article

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Invasive fungal infections (IFI) have been a leading cause of morbidity and infection-related mortality among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients over the past two decades.1 During the last two decades, several new drugs for antifungal prophylaxis entered clinical practice, supported by results of prospective randomized trials and guidelines.2 Recommendations on primary prophylaxis of IFI in allo-HSCT recipients have been recently published by the GITMO, and are based on ‘IFI risk stratification’ according to the various types and phases of HSCT.3 In agreement with the international guidelines, prophylaxis with a mold-active antifungal, such as voriconazole or posaconazole, is strongly recommended in high-risk patients, giving consideration to their relative efficacy, individual pharmacokinetic, drug–drug interaction and toxicity profiles.3

Posaconazole, a triazole with broad-spectrum antifungal activity and a favorable toxicity profile, approved by Food and Drug Administration for the prophylaxis of IFI in HSCT patients, is the recommended drug for patients with GvHD, with a high level of evidence.4 The oral solution formulation has the potential limitation of erratic oral absorption (in patients with intestinal GvHD and/or diarrhea), supporting the utility of therapeutic drug monitoring (TDM) in such conditions.5 Moreover, posaconazole prophylaxis in allo-HSCT recipients is normally administered in combination with drugs for GvHD prophylaxis and/or treatment, most commonly cyclosporine (CsA) or tacrolimus. On the basis of its cytochrome P450 3A4 (CYP3A4) inhibitory activity, posaconazole may increase the exposure to CsA, warranting a recommendation for close monitoring of blood CsA levels and subsequent CsA dose adjustment, as required.6 Sirolimus is an inhibitor of mammalian target of rapamycin used for GvHD prophylaxis and extensively metabolized by CYP3A4. As posaconazole strongly inhibits CYP3A4, its coadministration with sirolimus is discouraged by the manufacturer, though their clinical use has been poorly described in the literature thus far.7, 8, 9

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Acknowledgements

This work was supported by the Italian Ministry of Health (RF-2011-02351998). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Author contributions

RG, MCB and FC designed the study and analyzed the data. RG, MCB, MTLS, FG, MM, CM, AF, CO, SP, PS, SM, AA, MC, LV, CC, MB, JP and FC contributed to patient clinical care and data collection. RG, MCB and FC wrote the manuscript. All authors have approved the final version of the manuscript.

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Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy

    R Greco, M C Barbanti, MT Lupo Stranghellini, F Giglio, M Morelli, C Messina, A Forcina, S Piemontese, S Marktel, A Assanelli, M Carrabba, L Vago, C Corti, M Bernardi, J Peccatori & F Ciceri

  2. Infectious Disease Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy

    C Oltolini & P Scarpellini

  3. Unit of Immunogenetics, Leukemia Genomics and Immunobiology, IRCCS San Raffaele Scientific Institute, Milano, Italy

    L Vago

  4. University Vita-Salute, Milano, Italy

    F Ciceri

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  1. R Greco
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Correspondence to F Ciceri.

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Greco, R., Barbanti, M., Lupo Stranghellini, M. et al. Coadministration of posaconazole and sirolimus in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 51, 1022–1024 (2016). https://doi.org/10.1038/bmt.2016.112

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