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Details

Stereochemistry ABSOLUTE
Molecular Formula C52H74Cl2O18
Molecular Weight 1058.041
Optical Activity UNSPECIFIED
Defined Stereocenters 14 / 14
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FIDAXOMICIN

SMILES

CC[C@@]1([H])/C(/[H])=C(\C)/[C@]([H])(C/C(/[H])=C(\[H])/C(/[H])=C(\CO[C@@]2([H])[C@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C)O2)OC(=O)c3c(CC)c(c(c(c3O)Cl)O)Cl)O)OC)/C(=O)O[C@@]([H])(C/C(/[H])=C(\C)/C(/[H])=C(\C)/[C@]1([H])O[C@@]4([H])[C@]([H])([C@]([H])([C@@]([H])(C(C)(C)O4)OC(=O)C(C)C)O)O)[C@@]([H])(C)O)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

HIDE SMILES / InChI

Molecular Formula C52H74Cl2O18
Molecular Weight 1058.041
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 14 / 14
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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

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

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
DIFICID

Approved Use

Indicated in adults (≥18 years of age) for treatment of Clostridium difficile-associated diarrhea (CDAD).

Launch Date

1306454400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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
Disc. AE: Vomiting...
AEs leading to
discontinuation/dose reduction:
Vomiting (0.5%)
Sources:
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
Disc. AE: Hypersensitivity reaction, Multidrug resistant bacterial infection...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity reaction
Multidrug resistant bacterial infection
Sources:
AEs

AEs

AESignificanceDosePopulation
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
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
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
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak (co-administration study)
Comment: Human liver microsomes (S-mephenytoin); Coadministration of Fidaxomicin (200 mg BID) decreased Omeprazole (40 mg QD) Cmax by 7% and increased AUCinf by 3%
Page: 12, 38-39, 54-55, 100-109
weak
unlikely (co-administration study)
Comment: Human liver microsomes (testosterone, midazolam, nifedipine), direct inhibition (IC50 = 620 mcg/mL (testosterone), 42 mcg/mL (midazolam), time-dependent inhibition (IC50 = 78 mcg/mL (testosterone), 16 mcg/mL (midazolam); Coadministration of Fidaxomicin (200 mg BID) increased Lovastatin (10 mg QD) Cmax by 17% and AUCinf by 10%
Page: 33, 54-55, 56
yes [IC50 2.59 uM]
unlikely (co-administration study)
Comment: Caco-2 cells, IC50 = 2.73 mcg/mL; Coadministration of Fidaxomicin (200 mg BID) increased Digoxin (0.5 mg QD) Cmax by 14% and AUCinf by 11%
Page: 12, 33, 38, 58-60, 93-99
yes [IC50 >125 uM]
yes
yes
yes
yes
yes
yes
yes
no (co-administration study)
Comment: Human liver microsomes (diclofenac), IC50 = 7.2 mcg.mL; Coadministration of Fidaxomicin (200 mg BID) increased S-warfarin (Warfarin 10 mg QD) Cmax by 9% and AUCinf by 13%
Page: 12, 33, 38-39, 54-55, 100-109
yes
no (co-administration study)
Comment: Human liver microsomes (testosterone, midazolam, nifedipine), time-dependent inhibition, IC20 = 10 mcg/mL (testosterone), IC32 = 10 mcg/mL (midazolam 1'-hydroxylation), IC43 = 10 mcg/mL (nifedipine); Coadministration of Fidaxomicin (200 mg BID) decreased Midazolam (5 mg QD) Cmax by 8% and AUCinf by 4%
Page: 12, 33. 38-39, 54-55, 100-109
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
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.
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%.
Page: 12, 33, 34-37, 58-60, 84-92
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant).
2007 Jun
Patents

Patents

Sample Use Guides

One 200 mg tablet orally twice daily for 10 days with or without food
Route of Administration: Oral
In in vitro susceptibility test developed for fidaxomicin so that laboratories determining the susceptibility of C. difficile isolates to fidaxomicin can ascertain whether the susceptibility test is performing correctly the MICs were 0.03–0.25 ug/ml for C. difficile (ATCC 700057)
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:28:13 UTC 2021
Edited
by admin
on Fri Jun 25 22:28:13 UTC 2021
Record UNII
Z5N076G8YQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FIDAXOMICIN
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
DIFICID
Brand Name English
OPT-80
Code English
FIDAXOMICIN [USAN]
Common Name English
FIDAXOMICIN [INN]
Common Name English
FIDAXOMICIN [ORANGE BOOK]
Common Name English
PAR-101
Code English
FIDAXOMICIN [VANDF]
Common Name English
FIDAXOMICIN [WHO-DD]
Common Name English
FIDAXOMICIN [JAN]
Common Name English
FIDAXOMICIN [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC A07AA12
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
NDF-RT N0000175431
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
NCI_THESAURUS C261
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
WHO-VATC QA07AA12
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
FDA ORPHAN DRUG 325210
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
LIVERTOX 409
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
Code System Code Type Description
MERCK INDEX
M5378
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
4180
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
FDA UNII
Z5N076G8YQ
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
LACTMED
Fidaxomicin
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
CAS
873857-62-6
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
EVMPD
SUB31455
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
RXCUI
1111103
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
FIDAXOMICIN
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
PUBCHEM
10034073
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
DRUG BANK
DB08874
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
INN
9038
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
ChEMBL
CHEMBL1255800
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
NCI_THESAURUS
C66979
Created by admin on Fri Jun 25 22:28:13 UTC 2021 , Edited by admin on Fri Jun 25 22:28:13 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
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
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
EXCRETED UNCHANGED
FECAL
TARGET ORGANISM->INHIBITOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE LESS ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE DOSE

Biological Half-life PHARMACOKINETIC