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Expert Opinion on Pharmacotherapy Volume 6, 2005 - Issue 7
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Drug Evaluation

Voriconazole: review of a broad spectrum triazole antifungal agent

Grzegorz Kofla Humboldt University Berlin, Department of Medicine 2, Division of Oncology/Hematology, Charité Campus Mitte, Berlin, Germany. [email protected]
&
Markus Ruhnke Humboldt University Berlin, Department of Medicine 2, Division of Oncology/Hematology, Charité Campus Mitte, Berlin, Germany. [email protected]
Pages 1215-1229 | Published online: 15 Jun 2005

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  • •First report on the efficacy of voriconazole as salvage therapy in fluconazole refractory mucosal candidiasis in AIDS patients.
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  • •Detailed analysis on the efficacy of voriconazole as salvage therapy in invasive candidasis.
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  • •Addressing the potential problem of breakthrough fungal infections caused by Mucor spp. and C. glabrata.
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  • •Largest Candidemia study ever completed showing similar response rates as amphotericin B followed by fluconazole in 400 patients. According to these data, voriconazole was also licensed for this indication.
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  • ••Important animal model supporting theclinical evaluation of a combination therapy with voriconazole and caspofungin.
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  • ••Landmark study showing the superiority ofvoriconazole over amphotericin B in invasive aspergillosis.
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  • •Voriconazole is also effective in the therapy of invasive fungal infections in children.
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  • CORTEZ KJ, WALSH TJ, BENNETT JE:Successful treatment of coccidioidal meningitis with voriconazole. Clin. Infect. Dis. (2003) 36:1619–1622.
  • GARCI J, PERKINS A, GARAU M, GENE J, MOLINA L, DEL PALACIO A: Successful treatment with voriconazol of a Pseudallescheria boydii fungus ball in a HIV positive patient and previous tuberculosis. Rev. Iberoam. Micol (2003) 20(2):64–67.
  • PRABHU RM, BONNELL M, CURRIER BL, ORENSTEIN R: Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole. Clin. Infect. Dis. (2004) 39:e74–e77.
  • PERLROTH MG, MILLER J: Pseudoallescheria boydii pneumonia and empyema: a rare complication of heart transplantation cured with voriconazole. (2004) 23:647–649.
  • MELETIADIS J, MEIS JF, MOUTON JW et al.: In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob. Agents Chemother. (2002) 46(1):62–68.
  • CAPILLA J, GUARRO J: Correlation between in vitro susceptibility of Scedosporium apiospermum to voriconazole and in vivo outcome of scedosporiosis in guinea pigs. Antimicrob. Agents Chemother. (2004) 48:4009–4011.
  • NESKY MA, MCDOUGAL EC, PEACOCK JR JE: Pseudallescheria boydii brain abscess successfully treated with voriconazole and surgical drainage: case report and literature review of central nervous system pseudallescheriasis. Clin. Infect. Dis. (2000) 31:673–677.
  • •Brain abscesses caused by moulds such as P boydii can be cured with voriconazole. Aggressive strategies including neurosurgery are warranted.
  • HOWDEN BP, SLAVIN MA, SCHWARER AP, MUCH AM: Successful control of disseminated Scedosporium prohficans infection with a combination of voriconazole and terbinafine. Eur. j Clin. Microbiol Infect. Dis. (2003) 22:111–113.
  • MELETIADIS J, MOUTON JW, MEIS JF, VERWEIJ PE: In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedosporium prohficans isolates. Antimicrob. Agents Chemother. (2003) 47(1):106–117.
  • BIGLEY VT-I, DUARTE RF, GOSLING RD, KIBBLER CC, SEATON S, POTTER M: Fusarium dimerum infection in a stem cell transplant recipient treated successfully with voriconazole. Bone Marrow Transplant (2004) 34:815–817.
  • GUIMERA-MARTIN-NEDA F, GARCIA-BUSTINDUY M, NODA-CABRERA A, SANCHEZ-GONZALEZ R, MONTELONGO RG: Cutaneous infection by Fusarium: successful treatment with oral voriconazole. Br. J. Dermatol (2004) 150:777–778.
  • CUDILLO L, GIRMENIA C, SANTILLI S et al.: Breakthrough fitsariosis in a patient with acute lymphoblastic leukemia receiving voriconazole prophylaxis. Clin. Infect. Dis. (2005) 40:1212–1213.
  • BADEN LR, KATZ JT, FISHMAN JA et al.: Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy. Transplantation (2003) 76:1632–1637.
  • LI RK, CIBLAK MA, NORDOFF N, PASARELL L, WARNOCK DW, MCGINNIS MR: In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. Antimicrob. Agents Chemother. (2000) 44:1734–1736.
  • SCHLAMM HT, SUPPARATPINYO K: Voriconazole as therapy for systemic infections caused by Penicillium marneei in patients with HIV infection. 43rd Interscience Conference on Antimicrob. Agents Chemother. Chicago, IL, USA (2003) Abstract M–963.
  • PFALLER MA, MESSER SA, HOLLIS RJ, JONES RN, SENTRY PARTICIPANTS GROUP: Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob. Agents Chemother. (2002) 46:1032–1037.
  • •Important in vitro susceptibility data on the most recent azoles (voriconazole, posaconazole, ravuconazole) in clinical isolates supporting the efficacy of these newer agents against Aspergillus spp. but considerable differences against other filamentous fungi.
  • DANNAOUI E, MEIS JF, LOEBENBERG D, VERWEIJ PE: Activity of posaconazole in treatment of experimental disseminated zygomycosis. Antimicrob. Agents Chemother. (2003) 47:3647–3650.
  • SUN QN, NAJVAR LK, BOCANEGRA R, LOEBENBERG D, GRAYBILL JR: In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob. Agents Chemother. (2002) 46:2310–2312.
  • DANNAOUI E, MELETIADIS J, MOUTON JW, MEIS JF, VERWEIJ PE, EUROFUNG NETWORK: In vitro susceptibilities of zygomycetes to conventional and new antifitngals. J. Antimicrob. Chemother. (2003) 51(1):45–52.
  • MATTNER F, WEISSBRODT H, STRUEBER M: Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient. Scand J. Infect. Dis. (2004) 36:312–314.
  • SIWEK GT, DODGSON KJ, DE MAGALHAES-SILVERMAN M et al.: Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin. Infect. Dis. (2004) 39:584–587.
  • VIGOUROUX S, MORIN O, MOREAU P et al.: Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required. Clin. Infect. Dis. (2005) 40:e35–e37.
  • OREN I: Breakthrough zygomycosis duringempirical voriconazole therapy in febrile patients with neutropenia. Clin. Infect. Dis. (2005) 40:770–771.
  • KOBAYASHI K, KAMI M, MURASHIGO N, KISHI Y, FUJISAKI G, MITAMURAT: Breakthrough zygomycosis during voriconazole treatment for invasive aspergillosis. Haematologica (2004) 89:ECR42.
  • KONTOYIANNIS DP, LIONAKIS MS, LEWIS RE et al.: Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J. Infect. Dis. (2005) 191:1350–1359.
  • WALSH TJ, PAPPAS P, WINSTON DJ et al.: Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent Fever. N Engl. J. Med. (2002) 346(4):225–234.
  • ••Important study with conflicting resultsdue to complex study design (fewer breakthrough fungal infections with voriconazole as compared with AmBisome®, but according to a composite endpoint could not show noninferiority).
  • PEREA S, GONZALEZ G, FOTHERGILL AW, KIRKPATRICK WR, RINALDI MG, PATTERSON TF: In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob. Agents Chemother. (2002) 46:3039–3041.
  • CESARO S, TOFFOLUTTI T, MESSINA C et al.: Safety and efficacy of caspofungin and liposomal amphotericin B, followed by voriconazole in young patients affected by refractory invasive mycosis. Eur. Haematol (2004) 73:50–55.
  • MARR KA, BOECKH M, CARTER RA, KIM HJ, COREY L: Combination antifungal therapy for invasive aspergillosis. Clin. Infect. Dis. (2004) 39(6):797–802.
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Websites

  • http://www.fda.gov/ohrms/dockets/ac/01/ briefing/379213201Pfizer.pdf Background document for antiviral drug products advisory committee meeting: Vfend Voriconazole for intravenous injection, NDA 21–267 (2001).
  • http://www.emea.eu.int/humandocs/ Humans/EPARJvfend/vfend.htm European public assessment report (EPAR): Vfend: EMEA.

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