Echinocandins: A Promising New Class of Antifungal Agents

In an article published in the Journal of Pharmacy and Pharmacology, Akash Patil and Soumyajit Majumdar, MPharm, PhD, from the University of Mississippi, Oxford, discuss echinocandins, summarizing their antifungal activity, clinical trials’ results, dosage regimens, marketed formulations, adverse events and drug—drug interactions, and use in various subpopulations.

"Echinocandins present some advantages over the other classes of antifungal agents,” said Dr. Majumdar in an interview with Contagion^®. However, he added that when he and his colleague reviewed the literature on echinocandins, they found that a comprehensive compilation detailing the discovery, development, activity, delivery, and safety of this new class of antifungal agents was lacking.

"This information could help clinicians in the selection of the appropriate agents for the treatment of fungal diseases,” he emphasized.

According to Dr. Majumdar, one distinguishing feature of echinocandins is that their mechanism of action targets the fungal cell wall, unlike the azole or polyene classes of antifungal agents that target the fungal cell membrane.

The echinocandins— caspofungin, micafungin, and anidulafungin —“are fungicidal against Candida and Saccharomyces species, but fungistatic against Aspergillus species,” he said. “They have shown clinical success in the management of fungal infections, exhibiting acceptable safety and minimum adverse effects and drug—drug interactions.”

Indeed, the authors discuss that clinical studies have shown that all three echinocandins have equivalent, if not superior, efficacy to the traditional antifungal therapies involving amphotericin B and fluconazole.

Clinical trials have demonstrated success using echinocandins in the treatment of invasive candidiasis and aspergillosis with better safety and tolerability profiles in both adult and pediatric patient populations. However, the authors note that anidulafungin is currently not approved for use in pediatric patients.

Studies have also shown that clinicians do not need to make dose adjustments when treating geriatric patients with any of the echinocandins.

However, because the echinocandins can cross the placenta, clinicians should use these agents cautiously in pregnant women.

These agents have also caused rare and isolated hepatic side effects such as hepatic dysfunction, hepatitis, and hepatic failure. Thus, clinicians should carefully monitor patients with hepatic abnormalities who receive echinocandins. Clinicians may need to adjust the dose of caspofungin in particular when treating patients with hepatic insufficiency.

Because the echinocandins are not substrates for renal metabolism, clinicians do not need to adjust the doses of these agents in patients with renal insufficiency.

Although all three echinocandins are generally well-tolerated and safe for the treatment of fungal infections, anaphylaxis and anaphylactoid reactions (including shock) have also been observed with their use. Clinicians should, therefore, carefully monitor patients receiving echinocandin therapy.

Echinocandins are available commercially as lyophilized powders for reconstitution, the authors say. They are administered by slow intravenous (IV) infusion over a period of 1 hour to avoid any potential adverse effects, such as histamine-mediated or histamine-like reactions that could arise after fast IV infusion of these drugs.

Because echinocandins are poor substrates for CYP450 enzymes, and do not interact with P-glycoprotein transporters which control efflux of various drugs from cells, fewer drug—drug interactions are associated with echinocandins than with other antifungal agents. However, the authors note that cyclosporin administration has been shown to increase the area under the curve (AUC) of caspofungin and anidulafungin. Other clinically meaningful interactions have also been noted between caspofungin and tacrolimus or rifampin, as well as between micafungin and sirolimus or itraconazole.

However, despite the increased understanding of the echinocandins, including growing evidence in favor of their use in the treatment of invasive fungal infections, the authors emphasize that more research is needed to better understand these agents.

For example, “future studies on combination therapy (between different agents in the Echinocandin group or between different classes with different modes of action) and advanced drug delivery approaches would be interesting,” Dr. Majumdar concluded.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.