Clinical outcomes of oral suspension versus delayed-release tablet formulations of posaconazole for prophylaxis of invasive fungal infections

Jon P. Furuno, Gregory B. Tallman, Brie N. Noble, Joseph Bubalo, Graeme N. Forrest, James S. Lewis, Ana F. Bienvenida, Courtney A. Holmes, Bo R. Weber, Jessina C. McGregor

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayedrelease tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53% received the oral suspension and 48% received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69%), graft-versus-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6% and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95% confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 =g/ml. Posaconazole was discontinued early in 15.5% of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5%) and oral suspension (14.6%) formulations (95% CI for difference = -0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.

    Original languageEnglish (US)
    Article numbere00893
    JournalAntimicrobial Agents and Chemotherapy
    Volume62
    Issue number10
    DOIs
    StatePublished - Oct 1 2018

    Fingerprint

    Tablets
    Suspensions
    Incidence
    posaconazole
    Invasive Fungal Infections
    Confidence Intervals
    Myelodysplastic Syndromes
    Graft vs Host Disease
    Hematologic Neoplasms
    Acute Myeloid Leukemia
    Cohort Studies
    Retrospective Studies
    Demography
    Organizations
    Serum
    Research

    Keywords

    • Antifungal agents
    • Formulation
    • Invasive fungal infection
    • Medical outcomes
    • Posaconazole
    • Prophylaxis

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)
    • Infectious Diseases

    Cite this

    Clinical outcomes of oral suspension versus delayed-release tablet formulations of posaconazole for prophylaxis of invasive fungal infections. / Furuno, Jon P.; Tallman, Gregory B.; Noble, Brie N.; Bubalo, Joseph; Forrest, Graeme N.; Lewis, James S.; Bienvenida, Ana F.; Holmes, Courtney A.; Weber, Bo R.; McGregor, Jessina C.

    In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 10, e00893, 01.10.2018.

    Research output: Contribution to journalArticle

    Furuno, JP, Tallman, GB, Noble, BN, Bubalo, J, Forrest, GN, Lewis, JS, Bienvenida, AF, Holmes, CA, Weber, BR & McGregor, JC 2018, 'Clinical outcomes of oral suspension versus delayed-release tablet formulations of posaconazole for prophylaxis of invasive fungal infections', Antimicrobial Agents and Chemotherapy, vol. 62, no. 10, e00893. https://doi.org/10.1128/AAC.00893-18
    Furuno, Jon P. ; Tallman, Gregory B. ; Noble, Brie N. ; Bubalo, Joseph ; Forrest, Graeme N. ; Lewis, James S. ; Bienvenida, Ana F. ; Holmes, Courtney A. ; Weber, Bo R. ; McGregor, Jessina C. / Clinical outcomes of oral suspension versus delayed-release tablet formulations of posaconazole for prophylaxis of invasive fungal infections. In: Antimicrobial Agents and Chemotherapy. 2018 ; Vol. 62, No. 10.
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    abstract = "Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayedrelease tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53{\%} received the oral suspension and 48{\%} received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69{\%}), graft-versus-host disease (18{\%}), and myelodysplastic syndrome (3{\%}). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6{\%} and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95{\%} confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 =g/ml. Posaconazole was discontinued early in 15.5{\%} of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5{\%}) and oral suspension (14.6{\%}) formulations (95{\%} CI for difference = -0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.",
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    AU - Bubalo, Joseph

    AU - Forrest, Graeme N.

    AU - Lewis, James S.

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