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Eraxis(r) (Anidulafungin): A New Treatment Option for Candida Infections
Kristi Monson, PharmD candidate
The echinocandin antifungal medications are relatively new options for the treatment of fungal infections. Echinocandins are particularly useful as salvage therapy to treat Candida or Aspergillus infections when other antifungal therapies have failed or are not tolerated. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, which is essential to fungal cell wall structure but is not present in mammalian cells.1 This mechanism of action is distinct from that of amphotericin B and the azole antifungals. In addition to the first two echinocandins, caspofungin (Cancidas(r), Merck, & Co., Inc.) and micafungin (Mycamine(r), Astellas Pharma US), anidulafungin (Eraxis(r), Pfizer, Inc.) has recently become available. Anidulafungin was approved on February 17, 2006, for the treatment of esophageal candidiasis, candidemia, and other forms of Candida infections, such as intra-abdominal abscess and peritonitis.2
A randomized, double-blind, double-dummy study of 601 adults compared the efficacy and safety of intravenous anidulafungin with oral fluconazole for esophageal candidiasis. Patients aged 18 to 65 years with esophageal candidiasis and a predisposing risk factor for fungal infection, such as immunosuppression, were enrolled. Patients received either a 100 mg IV anidulafungin loading dose followed by 50 mg daily or a 200 mg oral fluconazole loading dose followed by 100 mg daily for 14 to 21 days. The primary endpoint was endoscopic success at the completion of therapy. Anidulafungin was non-inferior to fluconazole with 97.2% of patients achieving endoscopic success at the completion of therapy compared to 98.8% with fluconazole (treatment difference, -1.6%; 95% CI, -4.1 to 0.8). The intent-to-treat analysis showed similar results. Both treatments were well-tolerated, with headache and phlebitis being the most common treatment-related adverse events for anidulafungin (1.3% for both). The authors concluded that intravenous anidulafungin was as safe and effective as oral fluconazole for the treatment of esophageal candidiasis. This study was limited by the concurrent use of antiretroviral agents by more patients in the fluconazole group than in the anidulafungin group.3
According to the manufacturer, a randomized, double-blind study evaluated the efficacy and safety of intravenous anidulafungin versus intravenous fluconazole for the treatment of candidemia or other forms of invasive candidiasis. Two-hundred fifty-six patients were randomized to receive either a 200 mg anidulafungin loading dose followed by 100 mg daily or an 800 mg fluconazole loading dose followed by 400 mg daily for 14 to 42 days. The primary endpoint was global response at the end of treatment. For the modified intent-to-treat analysis, anidulafungin was more effective than fluconazole, with 75.6% and 60.2% global success rates, respectively (treatment difference, 15.42%; 95% CI, 3.9 to 27). This difference remained significant at the two-week follow-up but not at the six-week follow-up, with global success rates falling to 55.9% and 44.1% for anidulafungin and fluconazole, respectively (treatment difference, 11.84%; 95% CI, -3.4 to 27). Adverse event data was not reported.4
No drug interactions have been reported with anidulafungin, and no dosage adjustment is required for patients with renal or hepatic insufficiency. Anidulafungin is generally well-tolerated, with the most common adverse events being diarrhea (3.1%) and hypokalemia (3.1%). To treat esophageal candidiasis, a 100 mg IV loading dose is administered followed by 50 mg IV daily for at least 14 days and at least seven days after resolution of symptoms. For candidemia and other Candida infections, a 200 mg IV loading dose is administered, followed by 100 mg IV daily for at least 14 days after the last positive culture.4 Unlike caspofungin, anidulafungin is not indicated for use in invasive aspergillosis or for empiric therapy in febrile neutropenic patients.4,5
- Denning D. Echinocandin antifungal drugs. Lancet 2003;362:1142-1151.
- Goldberger M. Eraxis approval letter (2/17/06). Food and Drug Administration web site. Available at: http://www.fda.gov/cder/foi/appletter/2006/021948s000,021632s000ltr.pdf. Accessed August 18, 2006.
- 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;39:770-775.
- Eraxis [package insert]. New York, NY: Pfizer Inc.;2006 March.
- Cancidas [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.;2005 February.