Trade names Dificid, Dificlir Routes ofadministration Oral Molar mass 1,058.04 g/mol | License data US FDA: Fidaxomicin ATC code A07AA12 (WHO) | |
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Pregnancycategory AU: B1US: B (No risk in non-human studies) Legal status AU: S4 (Prescription only)CA: ℞-onlyUK: POM (Prescription only)US: ℞-only | ||
How to pronounce fidaxomicin dificid memorizing pharmacology flashcard
Fidaxomicin (trade names Dificid, Dificlir, and previously OPT-80 and PAR-101) is the first in a new class of narrow spectrum macrocyclic antibiotic drugs. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is non-systemic, meaning it is minimally absorbed into the bloodstream, it is bactericidal, and it has demonstrated selective eradication of pathogenic Clostridium difficile with minimal disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon can reduce the probability of Clostridium difficile infection recurrence.
Contents
- How to pronounce fidaxomicin dificid memorizing pharmacology flashcard
- Mechanism
- Clinical trials
- Approvals and indications
- References
It is marketed by Cubist Pharmaceuticals after acquisition of its originating company Optimer Pharmaceuticals. The target use is for treatment of Clostridium difficile infection.
Fidaxomicin is available in a 200 mg tablet that is administered every 12 hours for a recommended duration of 10 days. Total duration of therapy should be determined by the patient's clinical status. It is currently one of the most expensive antibiotics approved for use. A standard course costs upwards of £1350.
Mechanism
Fidaxomicin binds to and prevents movement of the "switch regions" of bacterial RNA polymerase. Switch motion is important for opening and closing of the DNA:RNA clamp, a process that occurs throughout RNA transcription but especially during opening of double standed DNA during transcription initiation. 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 trial comparing it with oral vancomycin for the treatment of Clostridium difficile infection (CDI) 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 CDI therapy 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 current standard-of-care, vancomycin, for treating CDI in a Phase III 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.
Approvals and indications
For the treatment of Clostridium difficile-associated diarrhea (CDAD), the drug won an FDA advisory panel's unanimous approval on April 5, 2011 and full FDA approval on May 27, 2011.