Drugs

, Volume 64, Issue 19, pp 2249–2258 | Cite as

Anidulafungin

Adis Drug Profile

Abstract

  • ▲ Anidulafungin is a novel antifungal agent which, like other echinocandins, inhibits β-(1,3)-D-glucan synthase and disrupts fungal cell-wall synthesis. It has marked antifungal activity against a broad spectrum of Candida spp. and Aspergillus spp., including amphotericin B- and triazole-resistant strains.

  • ▲ In clinical trials, anidulafungin has primarily been evaluated in patients with oesophageal and invasive candidiasis. Preliminary data are emerging for other indications such as invasive aspergillosis.

  • ▲ In a large, multicentre, double-blind, double-dummy, randomised trial in patients with oesophageal candidiasis, intravenous anidulafungin 50 mg/day was as effective as oral fluconazole 100 mg/day regarding end-of-treatment rates of endoscopic cure and clinical and microbiological success. Duration of treatment was approximately 2–3 weeks, and patients in both groups received a loading dose of study drug (twice the daily maintenance dose) on day 1.

  • ▲ Anidulafungin is generally well tolerated. Across the dosage range 50–100 mg/day, adverse events appear not to be dose- or infusion-related. In the largest clinical trial to date, the most common treatment-related adverse events were phlebitis/thrombophlebitis, headache, nausea, vomiting and pyrexia.

Keywords

Fluconazole Itraconazole Candidiasis Voriconazole Invasive Aspergillosis 

References

  1. 1.
    Denning DW, Kibbler CC, Barnes RA. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect Dis 2003 Apr; 3(4): 230–40PubMedCrossRefGoogle Scholar
  2. 2.
    Sobel JD. Practice guidelines for the treatment of fungal infections: Mycoses Study Group. Clin Infect Dis 2000; 30: 652PubMedCrossRefGoogle Scholar
  3. 3.
    Keating GM, Figgitt DP. Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis. Drugs 2003; 63(20): 2235–63PubMedCrossRefGoogle Scholar
  4. 4.
    Arathoon EG. Clinical efficacy of echinocandin antifungals. Curr Opin Infect Dis 2001 Dec; 14(6): 685–91PubMedCrossRefGoogle Scholar
  5. 5.
    Ruhnke M. Advances in the treatment of oral and esophageal candidiasis [abstract no. S15]. Clin Microbiol Infect 1999 Mar; 5 Suppl. 3: 6Google Scholar
  6. 6.
    Vazquez JA. Invasive oesophageal candidiasis: current and developing treatment options. Drugs 2003; 63(10): 971–89PubMedCrossRefGoogle Scholar
  7. 7.
    Feldmesser M. New and emerging antifungal agents: impact on respiratory infections. Am J Resp Med 2003; 2(5): 371–83CrossRefGoogle Scholar
  8. 8.
    Dismukes WE. Introduction to antifungal drugs. Clin Infect Dis 2000 Apr; 30(4): 653–7PubMedCrossRefGoogle Scholar
  9. 9.
    Jarvis B, Figgitt DP, Scott LJ. Micafungin. Drugs 2004; 64(9): 969–82PubMedCrossRefGoogle Scholar
  10. 10.
    Denning DW. Echinocandin antifungal drugs. Lancet 2003; 362(9390): 1142–51PubMedCrossRefGoogle Scholar
  11. 11.
    Hodges RL, Kelkar HS, Xuei X, et al. Characterization of an echinocandin B-producing strain blocked for sterigmatocystin biosynthesis reveals a translocation in the stcW gene of the aflatoxin biosynthetic pathway. J Ind Microbiol Biotechnol 2000 Dec; 25(6): 333–41PubMedCrossRefGoogle Scholar
  12. 12.
    Vicuron Pharmaceuticals Inc. Vicuron Pharmaceuticals announces phase III results of anidulafungin combination regimen for treatment of invasive aspergillosis [online]. Available from URL: http://www.vicuron.com [Accessed 2004 May 5]
  13. 13.
    Espinel-Ingroff A. Antifungal susceptibility methods and their potential clinical relevance. Lab Med 2002 Aug; 33(8): 626–31CrossRefGoogle Scholar
  14. 14.
    National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard (document M27-A). Wayne (PA): NCCLS, 1997; 17 (9)Google Scholar
  15. 15.
    Wiederhold NP, Lewis RE. The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy. Expert Opin Investig Drugs 2003 Aug; 12(8): 1313–33PubMedCrossRefGoogle Scholar
  16. 16.
    Green LJ, Marder P, Mann LL, et al. LY303366 exhibits rapid and potent fungicidal activity in flow cytometric assays of yeast viability. Antimicrob Agents Chemother 1999 Apr; 43(4): 830–5PubMedGoogle Scholar
  17. 17.
    Marco F, Pfaller MA, Messer SA, et al. Activity of MK-0991 (L-743,872), a new echinocandin, compared with those of LY303366 and four other antifungal agents tested against blood stream isolates of Candida spp. Diagn Microbiol Infect Dis 1998; 31: 33–7CrossRefGoogle Scholar
  18. 18.
    Karlowsky JA, Harding GA, Zelenitsky SA, et al. In vitro kill curves of a new semisynthetic echinocandin, LY-303366, against fluconazole-sensitive and -resistant Candida species. Antimicrob Agents Chemother 1997 Nov; 41(11): 2576–8PubMedGoogle Scholar
  19. 19.
    Pfaller MA, Messer SA, Coffman S. In vitro susceptibilities of clinical yeast isolates to a new echinocandin derivative, LY303366, and other antifungal agents. Antimicrob Agents Chemother 1997 Apr; 41(4): 763–6PubMedGoogle Scholar
  20. 20.
    Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother 2003 Oct; 47(10): 3149–54PubMedCrossRefGoogle Scholar
  21. 21.
    Marco F, Danés C, Almela M, et al. Trends in frequency and in vitro susceptibilities to antifungal agents, including voriconazole and anidulafungin, of Candida bloodstream isolates. Results from a six-year study (1996–2001). Diagn Microbiol Infect Dis 2003 Aug; 46(4): 259–64PubMedCrossRefGoogle Scholar
  22. 22.
    Arevalo MP, Carrillo-Muñoz AJ, Salgado J, et al. Antifungal activity of the echinocandin anidulafungin (VER002, LY-303366) against yeast pathogens: a comparative study with M27-A microdilution method. J Antimicrob Chemother 2003 Jan; 51(1): 163–6PubMedCrossRefGoogle Scholar
  23. 23.
    Cuenca-Estrella M, Mellado E, Díaz-Guerra TM, et al. Susceptibility of fluconazole-resistant clinical isolates of Candida spp. to echinocandin LY303366, itraconazole and amphotericin B. J Antimicrob Chemother 2000 Sep; 46(3): 475–7Google Scholar
  24. 24.
    Moore CB, Oakley KL, Denning DW. In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species. Clin Microbiol Infect 2001; 7: 11–6PubMedCrossRefGoogle Scholar
  25. 25.
    Johnson EM, Goldstein BP, Davey KG, et al. Comparison of the in vitro activity of anidulafungin with amphotericin B, caspofungin, fluconazole, itraconazole and voriconazole against a panel of 780 yeast isolates obtained from five European centres [abstract no. 513]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; PragueGoogle Scholar
  26. 26.
    Ernst EJ, Klepser ME, Pfaller MA. Postantifungal effects of echinocandin, azole, and polyene antifungal agents against Candida albicans and Cryptococcus neoformans. Antimicrob Agents Chemother 2000 Apr; 44(4): 1108–11Google Scholar
  27. 27.
    Zhanel GG, Saunders DG, Hoban DJ, et al. Influence of human serum on antifungal pharmacodynamics with Candida albicans. Antimicrob Agents Chemother 2001 Jul; 45(7): 2018–22PubMedCrossRefGoogle Scholar
  28. 28.
    Hoban D, Balko T, Saunders D, et al. Influence of human serum on Candida species susceptibility to LY303366 [abstract no. J-9]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San DiegoGoogle Scholar
  29. 29.
    Serrano MDC, Valverde-Conde A, Chavez M, et al. In vitro activity of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B against Aspergillus spp. Diagn Microbiol Infect Dis 2003 Feb; 45(2): 131–5CrossRefGoogle Scholar
  30. 30.
    Pfaller MA, Marco F, Messer SA, et al. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis 1998 Apr; 30(4): 251–5PubMedCrossRefGoogle Scholar
  31. 31.
    Brummer E, Chauhan SD, Stevens DA. Collaboration of human phagocytes with LY 303366 for antifungal activity against Aspergillus fumigatus. J Antimicrob Chemother 1999 Apr; 43(4): 491–6PubMedCrossRefGoogle Scholar
  32. 32.
    Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol 1998 Oct; 36(10): 2950–6PubMedGoogle Scholar
  33. 33.
    Zhanel GG, Karlowsky JA, Harding GA, et al. In vitro activity of a new semisynthetic echinocandin, LY-303366, against systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species. Antimicrob Agents Chemother 1997 Apr; 41(4): 863–5PubMedGoogle Scholar
  34. 34.
    Stevens DA. Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin synthase inhibitor (Nikkomycin Z) for inhibition and killing of fungal pathogens. Antimicrob Agents Chemother 2000 Sep; 44(9): 2547–8PubMedCrossRefGoogle Scholar
  35. 35.
    Philip A, Odabasi Z, Rodriguez JR, et al. In vitro synergy testing of anidulafungin (ANID) with itraconazole (ITR) and voriconazole (VOR) against Aspergillus spp. and Fusarium spp [abstract no. M-988]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; ChicagoGoogle Scholar
  36. 36.
    Ostrosky-Zeichner L, Matar M, Paetznick VL, et al. In-vitro synergy testing of anidulafungin (AFG) and micafungin (MFG) in combination with amphotericin B (AMB) against Aspergillus spp. and Fusarium spp [abstract no. M-1816]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 415Google Scholar
  37. 37.
    Karlowsky JA, Zelenitsky SA, Hoban DJ, et al. In vitro synergy determinations using an investigational echinocandin, LY303366, in combination with other systemic antifungal agents against Candida species [abstract no. F-70]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28–Oct 1; Toronto, 157Google Scholar
  38. 38.
    Walsh TJ, Viviani MA, Arathoon E, et al. New targets and delivery systems for antifungal therapy. Med Mycol 2000; 38 Suppl. 1: 335–47PubMedGoogle Scholar
  39. 39.
    Petraitiene R, Petraitis V, Groll AH, et al. Antifungal activity of LY303366, a novel echinocandin B, in experimental disseminated candidiasis in rabbits. Antimicrob Agents Chemother 1999 Sep; 43(9): 2148–55PubMedGoogle Scholar
  40. 40.
    Petraitis V, Petraitiene R, Groll AH, et al. Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis. Antimicrob Agents Chemother 2001 Feb; 45(2): 471–9PubMedCrossRefGoogle Scholar
  41. 41.
    Petraitis V, Petraitiene R, Groll AH, et al. Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother 1998 Nov; 42(11): 2898–905PubMedGoogle Scholar
  42. 42.
    Roberts J, Schock K, Marino S, et al. Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis. Antimicrob Agents Chemother 2000 Dec; 44(12): 3381–8PubMedCrossRefGoogle Scholar
  43. 43.
    Verweij PE, Oakley KL, Morrissey J, et al. Efficacy of LY303366 against amphotericin B-susceptible and -resistant Aspergillus fumigatus in a murine model of invasive aspergillosis. Antimicrob Agents Chemother 1998 Apr; 42(4): 873–8PubMedGoogle Scholar
  44. 44.
    Najvar LK, Bocanegra R, Sanche SE, et al. Efficacy of LY303366 (LY) in mice with itraconazole (ITRA)-resistant aspergillosis [abstract no. 2002]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San FranciscoGoogle Scholar
  45. 45.
    Rajman I, Desante K, Hatcher B, et al. LY303366 single intravenous dose pharmacokinetics and safety in healthy volunteers [abstract no. F-74]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28–Oct 1; Toronto, 158Google Scholar
  46. 46.
    Dowell J, Pu F, Lee J, et al. A clinical mass balance study of anidulafungin showing complete fecal elimination [abstract no. A-1576 and poster]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; ChicagoGoogle Scholar
  47. 47.
    Dowell J, Knebel W, Ludden T, et al. A population pharmacokinetic analysis of anidulafungin [abstract no. A-1575 and poster]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; ChicagoGoogle Scholar
  48. 48.
    Dowell J, Stogniew M, Krause D, et al. Anidulafungin (ANID) pharmacokinetic (PK)/pharmacodynamic (PD) correlation: treatment of esophageal candidiasis [abstract no. A-1578 and poster]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; ChicagoGoogle Scholar
  49. 49.
    Thye D, Kilfoil T, White RJ, et al. Anidulafungin: pharmacokinetics in subjects with mild and moderate hepatic impairment [abstract no. A-34 plus poster]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; ChicagoGoogle Scholar
  50. 50.
    Thye D, Marbury T, Kilfoil T, et al. Anidulafungin: pharmacokinetics in subjects receiving hemodialysis [abstract no. A-1390]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 19Google Scholar
  51. 51.
    Thye D, Marbury T, Kilfoil T, et al. Anidulafungin: pharmacokinetics in subjects with renal impairment [abstract no. A-1391]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 19Google Scholar
  52. 52.
    Thye D, Kilfoil T, Kilfoil G, et al. Anidulafungin: pharmacokinetics (PK) in subjects with severe hepatic impairment (HI) [abstract no. A-1392]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30, 19Google Scholar
  53. 53.
    Thye D, Kilfoil T, Kilfoil G, et al. Anidulafungin: safety and pharmacokinetics in subjects receiving concomitant cyclosporine [abstract no. A-1836]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 29Google Scholar
  54. 54.
    Dowell J, Schranz J, Wilson J, et al. Anidulafungin (ANID) pharmacokinetics are not affected by concomitant voriconazole (VORI) [abstract no. 1034]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; PragueGoogle Scholar
  55. 55.
    Dowell J, Schranz J, Stogniew M, et al. Assessment of the pharmacokinetics of anidulafungin in patients with invasive aspergillosis receiving concomitant liposomal amphotericin [abstract no. 1036]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; PragueGoogle Scholar
  56. 56.
    Stogniew M, Dowell J, Krause D, et al. Population pharmacokinetics confirms absence of anidulafungin drug-drug interactions [abstract no. 1035]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; PragueGoogle Scholar
  57. 57.
    Dowell JA, Knebel W, Ludden T, et al. Population pharmacokinetic analysis of anidulafungin, an echinocandin antifungal. J Clin Pharmacol 2004; 44: 590–8PubMedCrossRefGoogle Scholar
  58. 58.
    White RJ, Thye D. Anidulafungin does not affect the metabolism of cyclosporin by human hepatic microsomes [abstract no. A-35]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22–25; Chicago, 6Google Scholar
  59. 59.
    Stogniew M, Seng JE, Hoberman A, et al. Anidulafungin, a novel antifungal agent, produces no detectable toxicity when administered to DBA/2 and BALB/c mice, with or without cortisone acetate. King of Prussia (PA): Versicor, Inc., 2004. (Data on file)Google Scholar
  60. 60.
    Clemons KV, Sobel RA, Stevens DA. Toxicity of LY303366, an echinocandin antifungal, in mice pretreated with glucocorticoids. Antimicrob Agents Chemother 2000 Feb; 44(2): 378–81PubMedCrossRefGoogle Scholar
  61. 61.
    Krause DS, Simjee AE, van Rensburg C, et al. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis 2004; 39: 770–5PubMedCrossRefGoogle Scholar
  62. 62.
    Brown GL, White RJ, Turik M. Phase II, randomized, open label study of two intravenous dosing regimens of V-echinocandin in the treatment of esophageal candidiasis [abstract no. 1106]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; TorontoGoogle Scholar
  63. 63.
    Krause DS, Reinhardt J, Vazquez JA, et al. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrobial Agent and Chemotherapy 2004 Jun; 48(6): 2021–4CrossRefGoogle Scholar
  64. 64.
    Versicor Inc. Versicor announces positive phase III clinical trial results with anidulafungin for esophageal candidiasis [media release]. 2003 Mar 17Google Scholar
  65. 65.
    Laine L. The natural history of esophageal candidiasis after successful treatment in patients with AIDS. Gastroenterology 1994 Sep; 107(3): 744–6PubMedCrossRefGoogle Scholar
  66. 66.
    Krause D, Schranz J, Birmingham W. Lack of hepatic effect of anidulafungin [abstract no. 1789]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; PragueGoogle Scholar
  67. 67.
    Vicuron Pharmaceuticals Inc. Vicuron submits New Drug Application for anidulafungin to FDA [media release]. 2003 Apr 28Google Scholar
  68. 68.
    Vicuron Pharmaceuticals Inc. Vicuron Pharmaceuticals announces 90-day extension of FDA review of anidulafungin New Drug Application [media release]. 2004 Jan 22Google Scholar
  69. 69.
    Vicuron Pharmaceuticals Inc. Vicuron Pharmaceuticals files EMEA marketing application for anidulafungin [media release]. 2003Google Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

Personalised recommendations