Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C52H74Cl2O18 |
| Molecular Weight | 1058.039 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 14 / 14 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC[C@H]1\C=C(C)\[C@@H](O)C\C=C\C=C(CO[C@@H]2O[C@H](C)[C@@H](OC(=O)C3=C(O)C(Cl)=C(O)C(Cl)=C3CC)[C@H](O)[C@@H]2OC)\C(=O)O[C@@H](C\C=C(C)\C=C(C)\[C@@H]1O[C@@H]4OC(C)(C)[C@@H](OC(=O)C(C)C)[C@H](O)[C@@H]4O)[C@@H](C)O
InChI
InChIKey=ZVGNESXIJDCBKN-UUEYKCAUSA-N
InChI=1S/C52H74Cl2O18/c1-13-30-22-26(6)33(56)18-16-15-17-31(23-66-51-45(65-12)42(61)44(29(9)67-51)69-49(64)35-32(14-2)36(53)39(58)37(54)38(35)57)48(63)68-34(28(8)55)20-19-25(5)21-27(7)43(30)70-50-41(60)40(59)46(52(10,11)72-50)71-47(62)24(3)4/h15-17,19,21-22,24,28-30,33-34,40-46,50-51,55-61H,13-14,18,20,23H2,1-12H3/b16-15+,25-19+,26-22+,27-21+,31-17+/t28-,29-,30+,33+,34+,40-,41+,42+,43+,44-,45+,46+,50-,51-/m1/s1
| Molecular Formula | C52H74Cl2O18 |
| Molecular Weight | 1058.039 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 14 / 14 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/807545; https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002087/human_med_001511.jsp&mid=WC0b01ac058001d124
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/807545; https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002087/human_med_001511.jsp&mid=WC0b01ac058001d124
Fidaxomicin (trade names Dificid, Dificlir in Europe) is the first in a new class of narrow spectrum macrocyclic antibiotic drugs indicated for treatment of Clostridium difficile-associated diarrhea. Lipiarmycin (fidaxomicin), a metabolite of Actinoplanes deccanensis nov. sp. was first isolated in pure form in 1970s and was considered as antibiotic from its chemical and physico-chemical characteristics. It demonstrated high activity against Gram-positive bacteria, including strains resistant to the medically important antibiotics and protected mice experimentally infected with Streptococcus haemolyticus. 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. Although the exact mechanism of action has yet to be fully elucidated, fidaxomicin may bind to and inhibit bacterial DNA-dependent RNA polymerase, thereby inhibiting the initiation of bacterial RNA synthesis. When orally administered, this agent is minimally absorbed into the systemic circulation, acting locally in the gastrointestinal tract. Fidaxomicin appears to be active against pathogenic Gram-positive bacteria, such as clostridia, enterococci, and staphylococci, but does not appear to be active against other beneficial intestinal bacteria. The maintenance of normal physiological conditions in the colon can reduce the probability of Clostridium difficile infection recurrence. It is marketed by Cubist Pharmaceuticals after acquisition of its originating company Optimer Pharmaceuticals.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/807545
Curator's Comment: Lipiarmycin, a metabolite of Actinoplanes deccanensis nov. sp. has been isolated in pure form in 1970s and has been considered a new antibiotic. The compound was later being jointly developed by Optimer and Par Pharmaceuticals for the treatment of Clostridium difficile infections [https://www.ncbi.nlm.nih.gov/pubmed/?term=20509714]
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2363852 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | DIFICID Approved UseIndicated in adults (≥18 years of age) for treatment of Clostridium difficile-associated diarrhea (CDAD). Launch Date2011 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.2 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
62.9 ng × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11.7 h |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
FIDAXOMICIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Hypersensitivity reaction, Multidrug resistant bacterial infection... AEs leading to discontinuation/dose reduction: Hypersensitivity reaction Sources: Multidrug resistant bacterial infection |
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Vomiting... AEs leading to discontinuation/dose reduction: Vomiting (0.5%) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypersensitivity reaction | Disc. AE | 200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Multidrug resistant bacterial infection | Disc. AE | 200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Vomiting | 0.5% Disc. AE |
200 mg 2 times / day multiple, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=52 Page: 11, 26, 33, 52-53 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=18 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=19 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.pmda.go.jp/drugs/2018/P20180626001/800126000_23000AMX00480000_A100_1.pdf#page=19 Page: (PMDA in Japanese) 18-19 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
yes | likely (co-administration study) Comment: Caco-2 cells, efflux ratio = 73.9, Effluxes were decreased by >50% in the presence of test P-gp inhibitors, cyclosporine and ketoconazole; Coadministration of cyclosporine (200 mg x 1, P-gp inhibitor) increased Fidaxomicin (200 mg x 1) Cmax by 315% and AUCinf by 92%., Efficacy rates of fidaxomicin surpassed those of PO vancomycin for nearly all endpoints and analysis populations, regardless of P-gp inhibitor use. Fidaxomicin may be co-administered with P-gp inhibitors. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
yes | likely (co-administration study) Comment: Caco-2 cells, efflux ratio = 15.7; Coadministration of cyclosporine (P-gp inhibitor) increased Fidaxomicin Cmax by 851% and AUCinf by 311%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000ClinPharmR.pdf#page=34 Page: 12, 33, 34-37, 58-60, 84-92 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201699Orig1s000PharmR.pdf#page=30 Page: (Pharm) 30 |
Sample Use Guides
One 200 mg tablet orally twice daily for 10 days with or without food
Route of Administration:
Oral
| Substance Class |
Chemical
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Z5N076G8YQ
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C261
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QA07AA12
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NBK548928
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FIDAXOMICIN
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| Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE |
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EXCRETED UNCHANGED |
FECAL
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METABOLIC ENZYME -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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METABOLIC ENZYME -> INHIBITOR |
Fidaxomicin and OP-1118 exhibited inhibitory potential for prominent intestinal CYP isoenzymes (CYP3A4, CYP2C9, and CYP2C19) in in vitro studies with human liver microsomes, based on estimated intestinal concentrations (fidaxomicin [I]2, 800 ?g/mL).
IC50
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METABOLIC ENZYME -> INHIBITOR |
Fidaxomicin and OP-1118 exhibited inhibitory potential for prominent intestinal CYP isoenzymes (CYP3A4, CYP2C9, and CYP2C19) in in vitro studies with human liver microsomes, based on estimated intestinal concentrations (fidaxomicin [I]2, 800 ?g/mL).
IC50
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EXCRETED UNCHANGED |
FECAL
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TARGET ORGANISM->INHIBITOR |
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METABOLITE LESS ACTIVE -> PARENT |
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Tmax | PHARMACOKINETIC |
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| Biological Half-life | PHARMACOKINETIC |
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