CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2016; 37(01): 53-58
DOI: 10.4103/0971-5851.177032

Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia

Akash Shah
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Prasanth Ganesan
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Venkatraman Radhakrishnan
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Krishnarathinam Kannan
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Rejiv Rajendranath
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Vandana Mahajan
Department of Radiodiagnosis, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Varalakshmi Vijayakumar
Department of Microbiology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Trivadi Ganesan
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
Tenali Sagar
Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India
› Author Affiliations
Financial support and sponsorship Nil.


Background: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. Materials and Methods: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). Results: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. Conclusion: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole.

Publication History

Article published online:
12 July 2021

© 2016. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  • 1 Leventakos K, Lewis RE, Kontoyiannis DP. Fungal infections in leukemia patients: How do we prevent and treat them? Clin Infect Dis 2010;50:405-15.
  • 2 Viscoli C, Girmenia C, Marinus A, Collette L, Martino P, Vandercam B, et al. Candidemia in cancer patients: A prospective, multicenter surveillance study by the Invasive fungal infection group (IFIG) of the European organization for research and treatment of cancer (EORTC). Clin Infect Dis 1999;28:1071-9.
  • 3 Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: Systematic review of the literature. Clin Infect Dis 2001;32:358-66.
  • 4 Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: Ten years′ experience at a cancer center and implications for management. Blood 1997;90:999-1008.
  • 5 Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005;41:634-53.
  • 6 Denning DW, Marinus A, Cohen J, Spence D, Herbrecht R, Pagano L, et al. An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: Diagnosis and therapeutic outcome. EORTC invasive fungal infections cooperative group. J Infect 1998;37:173-80.
  • 7 Bow EJ, Loewen R, Cheang MS, Schacter B. Invasive fungal disease in adults undergoing remission-induction therapy for acute myeloid leukemia: The pathogenetic role of the antileukemic regimen. Clin Infect Dis 1995;21:361-9.
  • 8 Rotstein C, Bow EJ, Laverdiere M, Ioannou S, Carr D, Moghaddam N. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: Benefit based on purpose and intensity of cytotoxic therapy. The Canadian fluconazole prophylaxis study group. Clin Infect Dis 1999;28:331-40.
  • 9 Winston DJ, Chandrasekar PH, Lazarus HM, Goodman JL, Silber JL, Horowitz H, et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med 1993;118:495-503.
  • 10 Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000;110:273-84.
  • 11 von Eiff M, Roos N, Schulten R, Hesse M, Zühlsdorf M, van de Loo J. Pulmonary aspergillosis: Early diagnosis improves survival. Respiration 1995;62:341-7.
  • 12 Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis 2005;5:609-22.
  • 13 Menichetti F, Del Favero A, Martino P, Bucaneve G, Micozzi A, D′Antonio D, et al. Preventing fungal infection in neutropenic patients with acute leukemia: Fluconazole compared with oral amphotericin B. Ann Intern Med 1994;120:913-8.
  • 14 Perea S, Patterson TF. Antifungal resistance in pathogenic fungi. Clin Infect Dis 2002;35:1073-80.
  • 15 Gomes MZ, Mulanovich VE, Jiang Y, Lewis RE, Kontoyiannis DP. Incidence density of invasive fungal infections during primary antifungal prophylaxis in newly diagnosed acute myeloid leukemia patients in a tertiary cancer center, 2009 to 2011. Antimicrob Agents Chemother 2014;58:865-73.
  • 16 Vardakas KZ, Michalopoulos A, Falagas ME. Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: A meta-analysis of randomised-controlled trials. Br J Haematol 2005;131:22-8.
  • 17 Noxafil (Posaconazole) FDA Approval History - Available from: [Last cited 2014 Apr 24].
  • 18 Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007;356:348-59.
  • 19 Baden LR, Bensinger W, Angarone M, Casper C, Dubberke ER, Freifeld AG, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 2012;10:1412-45.
  • 20 Pagano L, Caira M, Candoni A, Aversa F, Castagnola C, Caramatti C, et al. Evaluation of the practice of antifungal prophylaxis use in patients with newly diagnosed acute myeloid leukemia: Results from the SEIFEM 2010-B registry. Clin Infect Dis 2012;55:1515-21.
  • 21 Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15.
  • 22 FDA Approves Antifungal Medicine Vfend - MedNews. Available from: [Last cited on 2014 Apr 24].
  • 23 De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-21.
  • 24 Common Terminology Criteria for Adverse Events v3.0. Available from: [Last cited on 2015 Sep 10].
  • 25 Mandhaniya S, Swaroop C, Thulkar S, Vishnubhatla S, Kabra SK, Xess I, et al. Oral voriconazole versus intravenous low dose amphotericin B for primary antifungal prophylaxis in pediatric acute leukemia induction: A prospective, randomized, clinical study. J Pediatr Hematol Oncol 2011;33:e333-41.
  • 26 Chabrol A, Cuzin L, Huguet F, Alvarez M, Verdeil X, Linas MD, et al. Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia. Haematologica 2010;95:996-1003.
  • 27 Vehreschild JJ, Böhme A, Buchheidt D, Arenz D, Harnischmacher U, Heussel CP, et al. A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). J Infect 2007;55:445-9.
  • 28 Gandham NR, Jadhav SV, Sardar M, Vyawahare C, Misra RR. The spectrum and aetiology of mycotic infections from a tertiary care hospital from Western part of India. J Clin Diagn Res 2013;7:2157-9.
  • 29 Chakrabarti A, Chatterjee SS, Shivaprakash MR. Overview of opportunistic fungal infections in India. Nihon Ishinkin Gakkai Zasshi 2008;49:165-72.
  • 30 Zonios DI, Gea-Banacloche J, Childs R, Bennett JE. Hallucinations during voriconazole therapy. Clin Infect Dis 2008;47:e7-10.
  • 31 Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 2008;46:201-11.
  • 32 Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol 2006; 46:235-43.
  • 33 Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002;34:563-71.
  • 34 Siopi M, Mavridou E, Mouton JW, Verweij PE, Zerva L, Meletiadis J. Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model. J Antimicrob Chemother 2014;69:1611-9.
  • 35 Owusu Obeng A, Egelund EF, Alsultan A, Peloquin CA, Johnson JA. CYP2C19 polymorphisms and therapeutic drug monitoring of voriconazole: Are we ready for clinical implementation of pharmacogenomics? Pharmacotherapy 2014;34:703-18.