Caspofungin Acetate: An Antifungal Agent

Anhthu Hoang


Am J Health Syst Pharm. 2001;58(13) 

In This Article

Abstract and Introduction

The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed.

Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3- -D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/µL. In another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%.

In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined.

Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.

Because of the growing population of immunocompromised patients, the incidence of fungal infections has increased significantly over the past 20 years, and fungi are now the fourth leading cause of nosocomial infections in the United States.[1] In a recent U.S. study of nosocomial bloodstream infections, mortality from Candida spp. was the highest (40%) of all infections. Within Candida spp., Candida albicans remained the most predominant pathogen (47%), followed by Candida glabrata (43%), Candida parapsilosis (21%), and Candida tropicalis (26%).

Available antifungal agents include amphotericin B, flucytosine, nystatin, and the azoles such as fluconazole and itraconazole. Although amphotericin B has been the mainstay of antifungal therapy for decades, its use is associated with significant adverse effects, such as nephrotoxicity, and infusion-related adverse events, including fever and chills. Introduction of liposomal forms of amphotericin B has resulted in less nephrotoxicity and fewer infusion-related adverse events, but these forms are significantly more expensive. Unlike other antifungal agents, the azoles produced less toxicity and thus changed the approach to treating fungal infections. Frequent use of fluconazole therapy, however, has led to increasing reports of treatment failure and resistant organisms, most notably in oropharyngeal candidiasis in patients with AIDS.[2] The development of novel antifungal therapies with broader-spectrum and more potent activity without significant toxicity has become fundamental to the future management of patients with fungal infections.


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