MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.
Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.
“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C. Yet “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus.”
A possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but “these things are not necessarily bad,” he added.
Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.
Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.
Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”
The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002;347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.
He and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.” The failure rate for invasive candidiasis decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.
Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.”