tedizolid phosphate 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
oxazolidinone antibacterials 4873 856867-55-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tedizolid phosphate
  • sivextro
  • torezolid phosphate
  • TR-701
Tedizolid phosphate is a prodrug that is converted by phosphatases to tedizolid, the microbiologically active moiety, following oral and intravenous administration. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely.
  • Molecular weight: 450.32
  • Formula: C17H16FN6O6P
  • CLOGP: -0.50
  • LIPINSKI: 1
  • HAC: 12
  • HDO: 2
  • TPSA: 152.79
  • ALOGS: -2.87
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O
0.20 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.10 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -1.774 High 0.81
caco2-efflux Caco-2 efflux ratio (BA/AB) 6.699 High 0.81
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.310 10^-6 cm/s High 0.81
dh-clint Dog hepatocyte intrinsic clearance 14.488 uL/min/10^6 cells High 0.81
dppb Dog plasma protein binding (% unbound) 11.390 % High 0.81
fcs-ppb Fetal calf serum protein binding (% unbound) 6.550 % High 0.81
herg hERG pIC50 4.535 pIC50 High 0.81
hh-clint Human hepatocyte intrinsic clearance 9.290 uL/min/10^6 cells High 0.81
hlm-clint Human liver microsomal intrinsic clearance 3.365 uL/min/mg protein High 0.81
hppb Human plasma protein binding (% unbound) 6.420 % High 0.81
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,GSK3B,ITK,JAK2,KDR,MAP2K6,MAP3K14,MAP3K7,MAPK10,MAPK7,MAPKAPK2,NTRK2,PDK1,PDK2,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKDC,SIK2,STK33,SYK,TEK,TGFBR1 39
kinase-selectivity-class AXL,CDK9,ERBB2,GRK2,MAP2K6,PRKDC,SYK 7
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.033 High 0.81
mh-clint Mouse hepatocyte intrinsic clearance 118.577 High 0.81
mppb Mouse plasma protein binding (% unbound) 16.630 High 0.81
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.341 High 0.81
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 8.640 % High 0.81
rh-clint Rat hepatocyte intrinsic clearance 57.677 uL/min/10^6 cells High 0.81
rh-fuinc Rat hepatocyte fraction unbound in incubation 79.330 % High 0.81
rppb Rat plasma protein binding (% unbound) 3.620 % High 0.81
solubility-dd Solubility at pH 7.4 in DMSO 931.108 uM High 0.81

Approvals:

DateAgencyCompanyOrphan
March 23, 2018 PMDA Bayer Yakuhin Ltd.
March 23, 2015 EMA Merck Sharp & Dohme Ltd
June 20, 2014 FDA CUBIST PHARMS INC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Product use in unapproved indication 105.35 71.95 49 482 184407 42436397
Vascular pseudoaneurysm thrombosis 81.39 71.95 10 521 77 42620727

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Product use in unapproved indication 138.27 60.76 68 816 447309 110141106
Thrombocytopenia 89.67 60.76 47 837 348838 110239577
Vascular pseudoaneurysm thrombosis 85.34 60.76 10 874 81 110588334
Off label use 63.83 60.76 68 816 1500117 109088298
Cardiac valve vegetation 60.99 60.76 10 874 1030 110587385

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J01XX11 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
OTHER ANTIBACTERIALS
Other antibacterials
FDA CS M0361132 Oxazolidinones
FDA EPC N0000175495 Oxazolidinone Antibacterial
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000900 Anti-Bacterial Agents
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
CHEBI has role CHEBI:33281 antimicrobial agent
CHEBI has role CHEBI:33282 antibacterial agent
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:48001 protein synthesis inhibitor
CHEBI has role CHEBI:49103 drug metabolite
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

J01XX Other antibacterials 12 drugs
bacitracinclofoctoldaptomycinfosfomycingepotidacinlefamulinlinezolidmandelic acidmethenaminenitroxolinespectinomycinxibornol

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Bacterial infection of skin indication 128936008
Streptococcal infection of skin indication 402937004
Staphylococcal infection of skin indication 402938009
Neutropenic disorder contraindication 303011007 DOID:1227




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 0.98 acidic
pKa2 6.03 acidic
pKa3 2.58 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
200MG SIVEXTRO CUBIST PHARMS LLC N205435 June 20, 2014 RX TABLET ORAL 8420676 Feb. 23, 2028 METHOD OF TREATING BACTERIAL INFECTIONS
200MG/VIAL SIVEXTRO CUBIST PHARMS LLC N205436 June 20, 2014 RX POWDER INTRAVENOUS 8420676 Feb. 23, 2028 METHOD OF TREATING BACTERIAL INFECTIONS
200MG SIVEXTRO CUBIST PHARMS LLC N205435 June 20, 2014 RX TABLET ORAL 7816379 June 20, 2028 METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA
200MG/VIAL SIVEXTRO CUBIST PHARMS LLC N205436 June 20, 2014 RX POWDER INTRAVENOUS 7816379 June 20, 2028 METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA
200MG SIVEXTRO CUBIST PHARMS LLC N205435 June 20, 2014 RX TABLET ORAL 9624250 Feb. 3, 2030 METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA
200MG/VIAL SIVEXTRO CUBIST PHARMS LLC N205436 June 20, 2014 RX POWDER INTRAVENOUS 9624250 Feb. 3, 2030 METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA
200MG SIVEXTRO CUBIST PHARMS LLC N205435 June 20, 2014 RX TABLET ORAL 8426389 Dec. 31, 2030 METHOD OF TREATING BACTERIAL INFECTIONS
200MG/VIAL SIVEXTRO CUBIST PHARMS LLC N205436 June 20, 2014 RX POWDER INTRAVENOUS 8426389 Dec. 31, 2030 METHOD OF TREATING BACTERIAL INFECTIONS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
200MG SIVEXTRO CUBIST PHARMS LLC N205435 June 20, 2014 RX TABLET ORAL April 4, 2028 NEW PATIENT POPULATION
200MG/VIAL SIVEXTRO CUBIST PHARMS LLC N205436 June 20, 2014 RX POWDER INTRAVENOUS April 4, 2028 NEW PATIENT POPULATION

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Amine oxidase [flavin-containing] B Enzyme IC50 5.24 CHEMBL
Amine oxidase [flavin-containing] A Enzyme IC50 5.06 CHEMBL

External reference:

IDSource
D09685 KEGG_DRUG
4033460 VUID
N0000190860 NUI
4033460 VANDF
4033461 VANDF
CHEBI:83326 CHEBI
U7V PDB_CHEM_ID
CHEMBL2105669 ChEMBL_ID
CHEMBL1257051 ChEMBL_ID
CHEMBL5314419 ChEMBL_ID
C515040 MESH_SUPPLEMENTAL_RECORD_UI
DB09042 DRUGBANK_ID
DB14569 DRUGBANK_ID
1540824 RXNORM
221941 MMSL
30367 MMSL
d08270 MMSL
015566 NDDF
015567 NDDF
703912007 SNOMEDCT_US
703913002 SNOMEDCT_US
703914008 SNOMEDCT_US
C2930762 UMLSCUI
C2744850 UMLSCUI
11476460 PUBCHEM_CID
856866-72-3 SECONDARY_CAS_RN
11234049 PUBCHEM_CID
10865 IUPHAR_LIGAND_ID
O7DRJ6R4DW UNII
9136 INN_ID
C546016 MESH_SUPPLEMENTAL_RECORD_UI
97HLQ82NGL UNII
CHEBI:82717 CHEBI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
SIVEXTRO HUMAN PRESCRIPTION DRUG LABEL 1 67919-040 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 200 mg INTRAVENOUS NDA 31 sections
SIVEXTRO HUMAN PRESCRIPTION DRUG LABEL 1 67919-041 TABLET, FILM COATED 200 mg ORAL NDA 31 sections
SIVEXTRO HUMAN PRESCRIPTION DRUG LABEL 1 72000-310 TABLET, FILM COATED 200 mg ORAL NDA 30 sections
SIVEXTRO HUMAN PRESCRIPTION DRUG LABEL 1 72000-320 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 200 mg INTRAVENOUS NDA 30 sections