|Trade names||Dificid, Dificlir|
|Other names||Clostomicin B1, lipiarmicin, lipiarmycin, lipiarmycin A3, OPT-80, PAR 01, PAR-101, tiacumicin B|
|Main uses||Clostridioides difficile diarrhea|
|Side effects||Nausea, constipation|
|Typical dose||200 mg BID|
|Bioavailability||Minimal systemic absorption|
|Elimination half-life||11.7 ± 4.80 hours|
|Excretion||Urine (<1%), faeces (92%)|
|Chemical and physical data|
|Molar mass||1058.05 g·mol−1|
|3D model (JSmol)|
Fidaxomicin, sold under the brand name Dificid among others, is an antibiotic used to treat Clostridioides difficile diarrhea. Evidence for use in severe disease is limited and in such cases vancomycin is preferred. It is taken by mouth.
Common side effects include nausea and constipation. Other side effects may include gastrointestinal bleeding, abdominal pain, allergic reaction, and liver problems. Safety in pregnancy and breastfeeding is unclear. It is a macrocyclic which works by blocking bacterial RNA polymerase.
Fidaxomicin was approved for medical use in the United States and Europe in 2011. In the United Kingdom a course of treatment costs the NHS about £1350 as of 2021. In the United States this amount costs about 4,150 USD. It is made from the actinomycete Dactylosporangium aurantiacum.
It is used for the treatment of Clostridium difficile infection, which is also known as Clostridium difficile-associated diarrhea or Clostridium difficile-associated illness (CDI), and can develop into Clostridium difficile colitis and pseudomembranous colitis.
Fidaxomicin is available in a 200 mg tablet that are taken every 12 hours for 10 days. Though total duration of therapy may be determined by the persons symptoms.
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.
Fidaxomicin is minimally absorbed into the bloodstream when taken by mouth, is bactericidal, and selectively eradicates pathogenic Clostridium difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridium difficile infection.
Society and culture
It is marketed by Merck, which acquired Cubist Pharmaceuticals in 2015, and had in turn bought the originating company, Optimer Pharmaceuticals.
On April 5, 2011, the drug won an FDA advisory panel's unanimous approval for the treatment of Clostridium 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).
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 Clostridium 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 'Clostridium 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 Clostridium 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 Clostridium 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 Clostridium difficile infection.
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