Mechanism
Fidaxomicin binds to and prevents movement of the "switch regions" of bacterial RNA polymerase. Switch motion occurs during the opening and closing of the DNA:RNA clamp, a process that occurs throughout RNA transcription but is especially important in the opening of double-stranded DNA during the initiation of transcription. It has minimal systemic absorption and a narrow spectrum of activity; it is active against Gram positive bacteria, especially clostridia. The minimal inhibitory concentration (MIC) range for ''C. difficile'' (ATCC 700057) is 0.03–0.25 μg/mL.Clinical trials
Good results were reported by the company in 2009, from a North American Phase III clinical trial comparing it with oral vancomycin for the treatment of '' Clostridioides difficile'' infection. The study met its primary endpoint of clinical cure, showing that fidaxomicin was non-inferior to oral vancomycin (92.1% vs. 89.8%). In addition, the study met its secondary endpoint of recurrence: 13.3% of the subjects had a recurrence with fidaxomicin vs. 24.0% with oral vancomycin. The study also met its exploratory endpoint of global cure (77.7% for fidaxomicin vs. 67.1% for vancomycin). ''Clinical cure'' was defined as patients requiring no further therapy for the treatment of ''C. difficile'' infection two days after completion of study medication. ''Global cure'' was defined as patients who were cured at the end of therapy and did not have a recurrence in the next four weeks. Fidaxomicin was shown to be as good as the standard-of-care, vancomycin, for treating ''Clostridioides difficile'' infection in a Phase III clinical trial published in February 2011. The authors also reported significantly fewer recurrences of infection, a frequent problem with ''C. difficile'', and similar drug side effects. Based on a multicenter clinical trial, fidaxomicin was reported well tolerated in children with ''Clostridioides difficile''–associated diarrhea and has a pharmacokinetic profile in children similar to that in adults. Regarding the high budget to spend for fidaxomicin, a systematic literature review published in 2017, showed that fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with ''Clostridioides difficile'' infection.Approvals and indications
On April 5, 2011, the drug won an FDA advisory panel's unanimous approval for the treatment of ''Clostridioides difficile'' infection, and gained full FDA approval on May 27, 2011. As of January 2020, fidaxomicin is FDA-approved for use in children aged 6 months and older for ''C. difficile'' associated diarrhea (CDAD).Adverse effects
The most common side effects reported in adults with the use of fidaxomicin include nausea, abdominal pain, vomiting, anemia, neutropenia, and gastrointestinal hemorrhage. In children the most common side effects include fever, vomiting, diarrhea, constipation, abdominal pain, rash, and increased aminotransferases.References
External links
* {{Portal bar , Medicine Chloroarenes Isobutyrate esters Macrolide antibiotics Merck & Co. brands Orphan drugs Phenols RNA polymerase inhibitors Antidiarrhoeals