Anidulafungin: a new echinocandin with a novel profile.
BACKGROUND
Until recently, available treatment for serious fungal infections comprised amphotericin B and azoles, which have limitations. Renal toxicity is a major concern with amphotericin B, while drug-drug interactions, hepatotoxicity, and skin rashes are the primary concerns with the azole medications. The development of the echinocandins, including caspofungin, has helped to fill the need for more efficacious antifungals that are useful across different patient populations and have a good safety profile. Anidulafungin is an echinocandin being developed to treat mucosal and invasive fungal infections.


OBJECTIVE
The aim of this report was to describe the pharmacodynamic and pharmacokinetic (PK) properties of anidulafungin.


METHODS
Data were identified using MEDLINE and National Library of Medicine Gateway searches for English-language literature (key words: anidulafungin, esophageal candidiasis, echinocandin, caspofungin, ravuconazole, voriconazole, posaconazole, micafungin, and fluconazole; years: 1996-2004), and from meeting abstracts of the American Society for Blood and Marrow Transplantation (Arlington Heights, Illinois), European Congress of Clinical Microbiology and Infectious Diseases (Basel, Switzerland), International Conference on Antimicrobial Agents and Chemotherapy (Washington, DC), and Infectious Diseases Society of America (Arlington, Virginia).


RESULTS
Anidulafungin has potent in vitro activity against Aspergillus and Candida spp, including those resistant to either fluconazole or amphotericin B. Results of several clinical trials imply that anidulafungin is effective in treating esophageal candidiasis (EC), candidemia, and invasive candidiasis (IC). In a Phase III, randomized, blinded clinical trial evaluating anidulafungin (50 mg/d) versus fluconazole (100 mg/d) for the treatment of EC, 97.2% and 98.9% of patients who received anidulafungin and fluconazole, respectively, showed evidence of cure or improvement (treatment difference, -1.6%; 95% CI, -4.1 to 0.8). In a Phase II study of candidasis and candidemia, anidulafungin showed success rates of 72%, 85%, and 83% in patients receiving the drug at dosages of 50, 75, or 100 mg/d, respectively. Studies evaluating the concomitant use of anidulafungin and either amphotericin, voriconazole, or cyclosporine did not show clinically significant drug-drug interactions or altered adverse-event (AE) profiles (P < 0.05). A population PK analysis showed no significant effect of age, race, concomitant medications, or renal or hepatic insufficiency on the PK properties of anidulafungin (P < 0.05).


CONCLUSIONS
Anidulafungin may offer a new option to treat serious fungal infections, such as EC, azole-refractory EC, candidemia, and IC. In addition, anidulafungin has been associated with no clinically significant drug-drug interactions and few treatment-related AEs. Anidulafungin may offer a new option in the management of serious and difficult-to-treat invasive fungal infections.
Vazquez
José A
JA
Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI 48202, USA. jvazque1@hfhs.org
D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D054714:Echinocandins; D006801:Humans; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D054714:Echinocandins; D010456:Peptides, Cyclic; D000077612:Anidulafungin