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Drug Evaluation

Posaconazole in prophylaxis and treatment of invasive fungal infections: a pharmacokinetic, pharmacodynamic and clinical evaluation

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Pages 539-550 | Received 06 Feb 2020, Accepted 01 May 2020, Published online: 01 Jun 2020

References

  • Brown GD, Denning DW, Gow NA, et al. Hidden killers: human fungal infections. Sci Transl Med. 2012 Dec 19;4(165):165rv13.
  • Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clinl Infect Dis. 2006;43(Supplement_1):S3–S14.
  • Lee CH, Lin C, Ho CL, et al. Primary fungal prophylaxis in hematological malignancy: a network meta-analysis of randomized controlled trials. Antimicrob Agents Chemother. 2018 Aug;62(8). DOI:10.1128/AAC.00355-18.
  • Maertens JA, Girmenia C, Bruggemann RJ, et al. European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European conference on infections in Leukaemia. J Antimicrob Chemother. 2018 Dec 1;73(12):3221–3230.
  • Maertens JA. Invasive Fungal Infections (Chapter 37). In: Carreras E, Dufour C, Mohty M et al., editors. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Cham (CH): Springer Copyright 2019, EBMT and the Author(s); 2019. p. 273–280.
  • Kurosawa M, Yonezumi M, Hashino S, et al. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol. 2012 Dec;96(6):748–757.
  • Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017 Mar;102(3):433–444.
  • Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1–e60.
  • Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European confederation of medical mycology in cooperation with the Mycoses Study GROUP education and research consortium. Lancet Infect Dis. 2019 Dec;19(12):e405–e421.
  • Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016 Jul;16(7):828–837.
  • Greenberg RN, Mullane K, van Burik JA, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006 Jan;50(1):126–133.
  • Krishna G, Ma L, Martinho M, et al. Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new tablet and capsule formulations relative to oral suspension. Antimicrob Agents Chemother. 2012 Aug;56(8):4196–4201.
  • Carmona EM, Limper AH. Overview of treatment approaches for fungal infections. Clin Chest Med. 2017 Sep;38(3):393–402.
  • Groll AH, Rijnders BJA, Walsh TJ, et al. Clinical pharmacokinetics, pharmacodynamics, safety and efficacy of liposomal amphotericin B. Clin Infect Dis. 2019 May 2;68(Supplement_4):S260–s274.
  • Adler-Moore J, Lewis RE, Bruggemann RJM, et al. Preclinical safety, tolerability, pharmacokinetics, pharmacodynamics, and antifungal activity of liposomal amphotericin B. Clin Infect Dis. 2019 May 2;68(Supplement_4):S244–s259.
  • Wiederhold NP. Antifungal resistance: current trends and future strategies to combat. Infect Drug Resist. 2017;10:249–259.
  • Van Daele R, Spriet I, Wauters J, et al. Antifungal drugs: what brings the future? Med Mycol. 2019 Jun 1;57(Supplement_3):S328–s343.
  • Perfect JR. The antifungal pipeline: a reality check. Nat Rev Drug Discov. 2017 Sep;16(9):603–616.
  • PubChem. Posaconazole. Compound summary. 2019 Dec. [cited 2019 Dec 12]. Available from: [https://pubchem.ncbi.nlm.nih.gov/compound/Posaconazole]
  • Percival KM, Bergman SJ. Update on posaconazole pharmacokinetics: comparison of old and new formulations. Curr Fungal Infect Rep. 2014 Jun 01;8(2):139–145.
  • Drugbank. Posaconazole. 2019 Dec. [cited 2019 Dec 12]. Available from: [https://www.drugbank.ca/drugs/DB01263]
  • Ezzet F, Wexler D, Courtney R, et al. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin Pharmacokinet. 2005;44(2):211–220.
  • European Medicines Agency. European public assessment report (EPAR) for Noxafil. [ cited 2019 Oct 16]. [cited 2019 Dec 12]. Available from: [https://www.ema.europa.eu/en/medicines/human/EPAR/noxafil]
  • Food and Drug Administration (FDA). Noxafil (posaconazole). Highlights of prescribing information. 2014. [cited 2019 Dec 12]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205596s000lbl.pdf
  • MSD. Summary of Product Characteristics (SmPC) Noxafil. 2019 dec. [cited 2019 Dec 12]. Available from: https://www.ema.europa.eu/en/documents/product-information/noxafil-epar-product-information_en.pdf
  • Hof H. A new, broad-spectrum azole antifungal: posaconazole–mechanisms of action and resistance, spectrum of activity. Mycoses. 2006;49(Suppl 1):2–6.
  • Herbrecht R. Posaconazole: a potent, extended-spectrum triazole anti-fungal for the treatment of serious fungal infections. Int J Clin Pract. 2004 Jun;58(6):612–624.
  • EUCAST. Rationale document for EUCAST clinical breakpoints. Posaconazole. Version 3.0 (2020). 2020. [cited 2020 Apr 19]. Available from: [http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Rationale_documents/Posaconazole_RD_v3.0_final_final_18_02.pdf]
  • Lewis RE, Albert ND, Kontoyiannis DP. Comparative pharmacodynamics of posaconazole in neutropenic murine models of invasive pulmonary aspergillosis and mucormycosis. Antimicrob Agents Chemother. 2014 Nov;58(11):6767–6772.
  • Seyedmousavi S, Mouton JW, Melchers WJ, et al. The role of azoles in the management of azole-resistant aspergillosis: from the bench to the bedside. Drug Resist Updat. 2014 Jul;17(3):37–50.
  • Kersemaekers WM, van Iersel T, Nassander U, et al. Pharmacokinetics and safety study of posaconazole intravenous solution administered peripherally to healthy subjects. Antimicrob Agents Chemother. 2015 Feb;59(2):1246–1251.
  • Arrieta AC, Sung L, Bradley JS, et al. A non-randomized trial to assess the safety, tolerability, and pharmacokinetics of posaconazole oral suspension in immunocompromised children with neutropenia. PLoS One. 2019;14(3):e0212837.
  • Lipp HP. Clinical pharmacodynamics and pharmacokinetics of the antifungal extended-spectrum triazole posaconazole: an overview. Br J Clin Pharmacol. 2010 Oct;70(4):471–480.
  • Courtney R, Pai S, Laughlin M, et al. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob Agents Chemother. 2003 Sep;47(9):2788–2795.
  • Ullmann AJ, Cornely OA, Burchardt A, et al. Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother. 2006 Feb;50(2):658–666.
  • Krishna G, Moton A, Ma L, et al. Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother. 2009 Mar;53(3):958–966.
  • Courtney R, Wexler D, Radwanski E, et al. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol. 2004 Feb;57(2):218–222.
  • Kohl V, Muller C, Cornely OA, et al. Factors influencing pharmacokinetics of prophylactic posaconazole in patients undergoing allogeneic stem cell transplantation. Antimicrob Agents Chemother. 2010 Jan;54(1):207–212.
  • Krishna G, AbuTarif M, Xuan F, et al. Pharmacokinetics of oral posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Pharmacotherapy. 2008 Oct;28(10):1223–1232.
  • Lebeaux D, Lanternier F, Elie C, et al. Therapeutic drug monitoring of posaconazole: a monocentric study with 54 adults. Antimicrob Agents Chemother. 2009 Dec;53(12):5224–5229.
  • Krishna G, Martinho M, Chandrasekar P, et al. Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Pharmacotherapy. 2007 Dec;27(12):1627–1636.
  • Dolton MJ, Ray JE, Chen SC, et al. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration. Antimicrob Agents Chemother. 2012 Nov;56(11):5503–5510.
  • Kim EJ, Yu KS, Na SH, et al. Risk factors for suboptimal drug concentration of posaconazole oral suspension in patients with hematologic malignancy. J Mycol Med. 2017 Dec;27(4):539–542.
  • Vanstraelen K, Prattes J, Maertens J, et al. Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients. Eur J Clin Pharmacol. 2016 Aug;72(8):953–963.
  • Kraft WK, Chang PS, van Iersel ML, et al. Posaconazole tablet pharmacokinetics: lack of effect of concomitant medications altering gastric pH and gastric motility in healthy subjects. Antimicrob Agents Chemother. 2014 Jul;58(7):4020–4025.
  • Kersemaekers WM, Dogterom P, Xu J, et al. Effect of a high-fat meal on the pharmacokinetics of 300-milligram posaconazole in a solid oral tablet formulation. Antimicrob Agents Chemother. 2015;59(6):3385–3389.
  • Cojutti PG, Candoni A, Lazzarotto D, et al. Co-administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed-released tablets in adult patients with haematological malignancies. Br J Clin Pharmacol. 2018 Nov;84(11):2544–2550.
  • Tang LA, Marini BL, Benitez L, et al. Risk factors for subtherapeutic levels of posaconazole tablet. J Antimicrob Chemother. 2017 Oct 1;72(10):2902–2905.
  • Gautier-Veyret E, Bolcato L, Roustit M, et al. Treatment by posaconazole tablets, compared to posaconazole suspension, does not reduce variability of posaconazole trough concentrations. Antimicrob Agents Chemother. 2019 Oct;63(10). DOI:10.1128/AAC.00484-19.
  • Blennow O, Eliasson E, Pettersson T, et al. Posaconazole concentrations in human tissues after allogeneic stem cell transplantation. Antimicrob Agents Chemother. 2014 Aug;58(8):4941–4943.
  • Conte JE Jr., Golden JA, Krishna G, et al. Intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole at steady state in healthy subjects. Antimicrob Agents Chemother. 2009 Feb;53(2):703–707.
  • Conte JE Jr., DeVoe C, Little E, et al. Steady-state intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole in lung transplant recipients. Antimicrob Agents Chemother. 2010 Sep;54(9):3609–3613.
  • Barde F, Billaud E, Goldwirt L, et al. Low central nervous system posaconazole concentrations during cerebral phaeohyphomycosis. Antimicrob Agents Chemother. 2019 Nov;63(11). DOI:10.1128/AAC.01184-19.
  • Ruping MJ, Albermann N, Ebinger F, et al. Posaconazole concentrations in the central nervous system. J Antimicrob Chemother. 2008 Dec;62(6):1468–1470.
  • Reinwald M, Uharek L, Lampe D, et al. Limited penetration of posaconazole into cerebrospinal fluid in an allogeneic stem cell recipient with invasive pulmonary aspergillosis. Bone Marrow Transplant. 2009 Aug;44(4):269–270.
  • Pitisuttithum P, Negroni R, Graybill JR, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother. 2005 Oct;56(4):745–755.
  • Krieter P, Flannery B, Musick T, et al. Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob Agents Chemother. 2004 Sep;48(9):3543–3551.
  • Ghosal A, Hapangama N, Yuan Y, et al. Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil). Drug Metab Dispos. 2004 Feb;32(2):267–271.
  • Wexler D, Courtney R, Richards W, et al. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci. 2004 Apr;21(5):645–653.
  • Shumaker AC, Bullard HM, Churpek J, et al. Posaconazole-digoxin drug-drug interaction mediated by inhibition of P-glycoprotein. J Oncol Pharm Pract. 2019 Oct;25(7):1758–1761.
  • Kim H, Kumari P, Laughlin M, et al. Use of high-performance liquid chromatographic and microbiological analyses for evaluating the presence or absence of active metabolites of the antifungal posaconazole in human plasma. J Chromatogr A. 2003 Feb 14;987(1–2):243–248.
  • Cornely OA, Duarte RF, Haider S, et al. Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J Antimicrob Chemother. 2016 Mar;71(3):718–726.
  • Jang SH, Colangelo PM, Gobburu JV. Exposure-response of posaconazole used for prophylaxis against invasive fungal infections: evaluating the need to adjust doses based on drug concentrations in plasma. Clin Pharmacol Ther. 2010 Jul;88(1):115–119.
  • Krishna G, Ma L, Martinho M, et al. A new solid oral tablet formulation of posaconazole: a randomized clinical trial to investigate rising single- and multiple-dose pharmacokinetics and safety in healthy volunteers. J Antimicrob Chemother. 2012 Nov;67(11):2725–2730.
  • van der Elst KC, Brouwers CH, van den Heuvel ER, et al. Subtherapeutic posaconazole exposure and treatment outcome in patients with invasive fungal disease. Ther Drug Monit. 2015 Dec;37(6):766–771.
  • Walsh TJ, Raad I, Patterson TF, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007 Jan 1;44(1):2–12.
  • Shields RK, Clancy CJ, Vadnerkar A, et al. Posaconazole serum concentrations among cardiothoracic transplant recipients: factors impacting trough levels and correlation with clinical response to therapy. Antimicrob Agents Chemother. 2011 Mar;55(3):1308–1311.
  • Sabatelli F, Patel R, Mann PA, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006 Jun;50(6):2009–2015.
  • Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009 Jan;53(1):24–34.
  • Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335–347.
  • Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348–359.
  • Dekkers BGJ, Bakker M, van der Elst KCM, et al. Therapeutic drug monitoring of posaconazole: an update. Curr Fungal Infect Rep. 2016;10:51–61.
  • Lewis R, Brüggemann R, Padoin C et al. Triazole antifungal therapeutic drug monitoring. ECIL-6 meeting; 2015 Sep 11-12; France.
  • Ashbee HR, Barnes RA, Johnson EM, et al. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for medical mycology. J Antimicrob Chemother. 2014 May;69(5):1162–1176.
  • Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 May;24(Suppl 1):e1–e38.
  • Boglione-Kerrien C, Picard S, Tron C, et al. Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies. J Cancer Res Clin Oncol. 2018 Jan;144(1):127–134.
  • Schauwvlieghe A, Buil JB, Verweij PE, et al. High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections. Mycoses. 2020 Feb;63(2):122–130.
  • European Medicines Agency (EMA). Noxafil IV. Assessment report. 2014 Jul 24.
  • European Medicines Agency (EMA). Noxafil Gastro-resistant tablet. Assessment report. 2014.
  • Parkes LO, Cheng MP, Sheppard DC. Visual hallucinations associated with high posaconazole concentrations in serum. Antimicrob Agents Chemother. 2016;60:1170–1171. United States.
  • Nguyen MH, Davis MR, Wittenberg R, et al. Posaconazole serum drug levels associated with pseudohyperaldosteronism. Clin Infect Dis. 2019 Aug 12. DOI:10.1093/cid/ciz741.
  • Tverdek FP, Heo ST, Aitken SL, et al. Real-life assessment of the safety and effectiveness of the new tablet and intravenous formulations of posaconazole in the prophylaxis of invasive fungal infections via analysis of 343 courses. Antimicrob Agents Chemother. 2017 Aug;61(8). DOI:10.1128/AAC.00188-17.
  • Bryant AM, Slain D, Cumpston A, et al. A post-marketing evaluation of posaconazole plasma concentrations in neutropenic patients with haematological malignancy receiving posaconazole prophylaxis. Int J Antimicrob Agents. 2011 Mar;37(3):266–269.
  • Oh J, Kang CI, Kim SH, et al. Antifungal prophylaxis with posaconazole tablet and oral suspension in patients with haematologic malignancy: therapeutic drug monitoring, efficacy and risk factors for the suboptimal level. Mycoses. 2020 Jan;63(1):89–94.
  • Thompson GR 3rd, Rinaldi MG, Pennick G, et al. Posaconazole therapeutic drug monitoring: a reference laboratory experience. Antimicrob Agents Chemother. 2009 May;53(5):2223–2224.
  • Tonini J, Thiebaut A, Jourdil JF, et al. Therapeutic drug monitoring of posaconazole in allogeneic hematopoietic stem cell transplantation patients who develop gastrointestinal graft-versus-host disease. Antimicrob Agents Chemother. 2012 Oct;56(10):5247–5252.
  • Dolton MJ, Ray JE, Marriott D, et al. Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring. Antimicrob Agents Chemother. 2012 Jun;56(6):2806–2813.
  • Cornely OA, Ullmann AJ. Lack of evidence for exposure-response relationship in the use of posaconazole as prophylaxis against invasive fungal infections. Clin Pharmacol Ther. 2011;89:351–352. United States.
  • Courtney R, Sansone A, Smith W, et al. Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease. J Clin Pharmacol. 2005 Feb;45(2):185–192.
  • Morris AA, Mueller SW, Rower JE, et al. Evaluation of sulfobutylether-beta-cyclodextrin exposure in a critically Ill patient receiving intravenous posaconazole while undergoing continuous venovenous hemofiltration. Antimicrob Agents Chemother. 2015 Oct;59(10):6653–6656.
  • Moton A, Krishna G, Ma L, et al. Pharmacokinetics of a single dose of the antifungal posaconazole as oral suspension in subjects with hepatic impairment. Curr Med Res Opin. 2010 Jan;26(1):1–7.
  • Food and Drug Administration (FDA). Pediatric postmarketing pharmacovigilance review. 2018. [cited 2019 Dec 12]. Available from: https://www.fda.gov/media/114097/download
  • Wasmann RE, Smit C, van Donselaar MH, et al. Implications for IV posaconazole dosing in the era of obesity. J Antimicrob Chemother. 2020 Apr 1;75(4):1006–1013.
  • Smith BS, Yogaratnam D, Levasseur-Franklin KE, et al. Introduction to drug pharmacokinetics in the critically ill patient. Chest. 2012 May;141(5):1327–1336.
  • Ray J, Campbell L, Rudham S, et al. Posaconazole plasma concentrations in critically ill patients. Ther Drug Monit. 2011 Aug;33(4):387–392.
  • Sime FB, Stuart J, Butler J, et al. Pharmacokinetics of intravenous posaconazole in critically Ill patients. Antimicrob Agents Chemother. 2018 Mar 26;62(6):pii: e00242-18.
  • Sansone-Parsons A, Krishna G, Simon J, et al. Effects of age, gender, and race/ethnicity on the pharmacokinetics of posaconazole in healthy volunteers. Antimicrob Agents Chemother. 2007 Feb;51(2):495–502.
  • Amsden JR, Gubbins PO. Pharmacogenomics of triazole antifungal agents: implications for safety, tolerability and efficacy. Expert Opin Drug Metab Toxicol. 2017 Nov;13(11):1135–1146.
  • Suh HJ, Yoon SH, Yu KS, et al. The genetic polymorphism UGT1A4*3 is associated with low posaconazole plasma concentrations in hematological malignancy patients receiving the oral suspension. Antimicrob Agents Chemother. 2018 Jul;62(7):pii:e02230-17.
  • Wilson DT, Dimondi VP, Johnson SW, et al. Role of isavuconazole in the treatment of invasive fungal infections. Ther Clin Risk Manag. 2016;12:1197–1206.
  • Sansone-Parsons A, Krishna G, Martinho M, et al. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy. 2007 Jun;27(6):825–834.
  • Dahlen T, Kalin M, Cederlund K, et al. Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes. Eur J Haematol. 2016 Feb;96(2):175–180.
  • Tormo M, Perez-Martinez A, Calabuig M, et al. Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high-risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: A real-world comparison. Mycoses. 2018 Mar;61(3):206–212.
  • Leonart LP, Tonin FS, Ferreira VL, et al. A network meta-analysis of primary prophylaxis for invasive fungal infection in haematological patients. J Clin Pharm Ther. 2017 Oct;42(5):530–538.
  • Su HC, Hua YM, Feng IJ, et al. Comparative effectiveness of antifungal agents in patients with hematopoietic stem cell transplantation: a systematic review and network meta-analysis. Infect Drug Resist. 2019;12:1311–1324.
  • Fontana L, Perlin DS, Zhao Y, et al. Isavuconazole prophylaxis in patients with hematologic malignancies and hematopoietic cell transplant recipients. Clin Infect Dis. 2020 Feb 14;70(5):723–730.
  • Cornely OA, Robertson MN, Haider S, et al. Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. J Antimicrob Chemother. 2017 Dec 1;72(12):3406–3413.

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