June 8, 2011 — The US Food and Drug Administration (FDA) approved the macrolide antibacterial fidaxomicin (Dificid, Optimer Pharmaceuticals Inc) for the treatment of Clostridium difficile–associated diarrhea (CDAD).

Safe, Effective Drug

Approval of fidaxomicin tablets was based on 2 trials involving 564 patients with CDAD. In those trials, fidaxomicin was shown to have an efficacy and safety similar to those of vancomycin.

The trials also showed that more patients treated with fidaxomicin had a sustained response 3 weeks after treatment ended than patients treated with vancomycin. The most common adverse effects included nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%).

In April this year, on reviewing results of the 2 studies, the FDA's Anti-Infective Drugs Advisory Committee unanimously recommended fidaxomicin for the treatment of life-threatening C difficile–associated diarrhea.

"In recent years, many in the infectious disease community have seen an increase in the number of cases of people with a C difficile infection," noted Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, in a news release. "[Fidaxomicin] is an effective new treatment option for patients who develop Clostridium difficile–associated diarrhea."

Fidaxomicin should be taken as one 200-mg film-coated tablet orally twice daily for 10 days with or without food. To reduce the development of drug-resistant bacteria, fidaxomicin should be used to treat only infections that are proven or strongly suspected to be caused by C difficile, and it should not be used for systemic infections. Otherwise, there are no contraindications.

According to the FDA, C difficile is a bacterium that can cause diarrhea and result in serious intestinal conditions, such as colitis and, in some cases, death. "C difficile bacteria are found in the stool of an infected person, and others can become infected if they touch items or surfaces contaminated with the bacteria or spores and then touch their mouths," the FDA states.

Comparison to Vancomycin

"Fidaxomicin is the second drug (after vancomycin) approved by the FDA for C difficile-associated diarrhea," said John Bartlett, MD, chief of the Division of Infectious Diseases at Johns Hopkins University School of Medicine in Baltimore, Maryland. "The special advantage of fidaxomicin is that it reduces the frequency of relapses, which is a big problem with [C difficile infection]," Dr. Bartlett told Medscape Medical News.

According to Dr. Bartlett, the biologic basis of fidaxomicin is that it is not absorbed, so all that is put in the mouth goes right to the colon. "It is very active against [C difficile infection] since there are no resistant strains with in vitro testing — and it is unlikely that there ever will be resistance," he said.

Vancomycin has the same properties, but it also has a major effect on fecal flora, causing relapse when the drug is stopped. "Vancomycin both causes and cures C difficile diarrhea and colitis. By contrast, fidaxomicin has much less impact on the fecal flora, so it makes sense that relapses would be less frequent," Dr. Bartlett said.

The 2 drugs are comparable with respect to initial treatment, however, and cost will be an issue, as fidaxomicin is substantially more expensive than vancomycin, which is available as a generic, although the more expensive parvule form is sold in drug stores. "Fidaxomicin should largely replace that product, at least until the vancomycin parvule patent comes off," Dr. Bartlett said.

Special Populations

The safety and efficacy of fidaxomicin have not been studied in patients younger than 18 years. In controlled trials of fidaxomicin, 50% of patients were 65 years and older, and 31% were 75 years and older. There were no overall differences in the safety or efficacy of fidaxomicin vs vancomycin between these patients and younger participants.

Fidaxomicin is pregnancy Category B, meaning that it should be used during pregnancy only if clearly needed. Rabbit studies have shown no evidence of harm to the fetus from fidaxomicin, but there have been no adequate and well-controlled studies in pregnant women. Because it is not known whether fidaxomicin is excreted in human milk, caution should be exercised when it is given to a woman who is breast-feeding.

More information on fidaxomicin is available on the FDA Web site.

Laurie Barclay, MD, contributed to this news article.

Clinical Implications

• Fidaxomicin is a macrolide antibiotic approved by the FDA for the treatment of CDAD. It should be taken as one 200-mg film-coated tablet orally twice daily for 10 days with or without food, and it should be used to treat only infections that are proven or strongly suspected to be caused by C difficile.
• In clinical trials leading to approval, fidaxomicin was shown to have an efficacy and safety similar to those of vancomycin, but more patients treated with fidaxomicin had a sustained response 3 weeks after treatment ended than patients treated with vancomycin. The most common adverse effects were nausea, vomiting, abdominal pain, gastrointestinal hemorrhage, anemia, and neutropenia.
• The safety and efficacy of fidaxomicin have not been studied in patients younger than 18 years. In controlled trials, there were no overall differences in the safety or efficacy of fidaxomicin vs vancomycin between patients 65 years and older vs younger participants. Fidaxomicin is pregnancy Category B, and caution should be exercised when the drug is given to a woman who is breast-feeding.

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