| Systematic (IUPAC) name | |
|---|---|
| 3-(((6-Deoxy-4-O-(3,5-dichloro-2-ethyl-4,6-dihydroxybenzoyl)-2-O-methyl-β-D-mannopyranosyl)oxy)-methyl)-12(R)-[(6-deoxy-5-C-methyl-4-O-(2-methyl-1-oxopropyl)-β-D-lyxo-hexopyranosyl)oxy]-11(S)-ethyl-8(S)-hydroxy-18(S)-(1(R)-hydroxyethyl)-9,13,15-trimethyloxacyclooctadeca-3,5,9,13,15-pentaene-2-one | |
| Clinical data | |
| Trade names | Dificid |
| Licence data | US FDA:link |
| Pregnancy cat. | B(US) |
| Legal status | ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Half-life | 11.7 ± 4.80 hours |
| Excretion | Feces (92%), urine (0.59%)[1] |
| Identifiers | |
| CAS number | 873857-62-6 |
| ATC code | None |
| PubChem | CID 11528171 |
| UNII | Z5N076G8YQ |
| KEGG | D09394 |
| ChEMBL | CHEMBL1255800 |
| Synonyms | Clostomicin B1, lipiarmicin, lipiarmycin, lipiarmycin A3, OPT 80, PAR 01, PAR 101, tiacumicin B |
| Chemical data | |
| Formula | C52H74Cl2O18 |
| Mol. mass | 1058.04 g/mol |
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Fidaxomicin (trade name Dificid, and previously OPT-80 and PAR-101) is the first in a new class of narrow spectrum macrocyclic antibiotic drugs.[2] It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis.[1][3] 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.[4][5]
It is marketed by Optimer Pharmaceuticals 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 works by inhibiting the bacterial enzyme RNA polymerase, resulting in the death of Clostridium difficile.[6] 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).[1]
Good results were reported in 2009 from a North American phase III trial comparing it with oral vancomycin for the treatment of Clostridium difficile infection (CDI)[7][8] 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).[9] 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 4 weeks.[10]
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.[11] The authors also reported significantly fewer recurrences of infection, a frequent problem with C. difficile, and similar drug side effects.
The drug won an FDA advisory panel's unanimous approval on April 10, 2011.[12] and full FDA approval on May 27, 2011.[13]