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

Stem definitionDrug idCAS RN
systemic antifungal agents, miconazole derivatives 4947 742049-41-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • isavuconazonium
  • isavuconazonium sulfate
  • isavuconazonium chloride
  • cresemba
  • BAL8557-000
  • BAL8557-002
  • RO0098557
prodrug of BAL4815
  • Molecular weight: 717.77
  • Formula: C35H35F2N8O5S
  • CLOGP: -0.61
  • LIPINSKI: 2
  • HAC: 13
  • HDO: 2
  • TPSA: 159.37
  • ALOGS: -5.16
  • ROTB: 15
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O
0.20 g P

ADMET properties:

PropertyValueReference
BA (Bioavailability) 100 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.267 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 37.844 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 3.076 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 7.516 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 24.880 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 34.570 % High 1
herg hERG pIC50 5.021 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 15.066 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 244.906 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 28.800 % High 1
kinase-safety-class EIF2AK3,GRK2,PDK1,PDK2,PDK4 5
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 26.607 High 1
mh-clint Mouse hepatocyte intrinsic clearance 76.033 High 1
mppb Mouse plasma protein binding (% unbound) 21.950 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 47.753 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 43.360 % High 1
rh-clint Rat hepatocyte intrinsic clearance 52.119 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 57.150 % High 1
rppb Rat plasma protein binding (% unbound) 21.320 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 335.738 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 23, 2015 EMA
March 6, 2015 FDA ASTELLAS
Dec. 23, 2022 PMDA Asahi Kasei Pharma Corporation

FDA Adverse Event Reporting System (Female)

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
Off label use 340.86 32.31 215 1331 1102037 89524864
Febrile neutropenia 42.76 32.31 29 1517 158320 90468581
Death 38.66 32.31 43 1503 456508 90170393
Hypoxia 34.27 32.31 19 1527 72380 90554521

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
Off label use 415.00 27.05 355 2887 637980 41980113
Febrile neutropenia 103.14 27.05 96 3146 185607 42432486
Aspergillus infection 61.40 27.05 28 3214 15809 42602284
Lip squamous cell carcinoma 57.59 27.05 10 3232 143 42617950
Pneumonia fungal 34.90 27.05 16 3226 9130 42608963
Human herpesvirus 8 infection 30.46 27.05 9 3233 1488 42616605

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
Off label use 244.74 26.17 303 4296 1499882 109084818
Febrile neutropenia 155.10 26.17 118 4481 316649 110268051
Aspergillus infection 78.05 26.17 32 4567 25584 110559116
Lip squamous cell carcinoma 56.00 26.17 10 4589 318 110584382
Death 55.71 26.17 102 4497 698767 109885933
Disease progression 53.50 26.17 58 4541 243976 110340724
Septic shock 46.51 26.17 44 4555 157484 110427216
Gamma-glutamyltransferase increased 41.72 26.17 28 4571 61281 110523419
Cytokine release syndrome 40.54 26.17 29 4570 70277 110514423
Pneumonia fungal 40.11 26.17 17 4582 14737 110569963
Human herpesvirus 8 infection 33.84 26.17 9 4590 1862 110582838
Drug interaction 30.08 26.17 65 4534 500118 110084582
Product use in unapproved indication 29.05 26.17 60 4539 447317 110137383
Sepsis 28.81 26.17 50 4549 327296 110257404
Bronchopulmonary aspergillosis 28.75 26.17 17 4582 29846 110554854
Drug level increased 28.23 26.17 20 4579 47699 110537001
Multiple organ dysfunction syndrome 27.99 26.17 33 4566 151677 110433023
Product administered to patient of inappropriate age 27.78 26.17 11 4588 8025 110576675
Respiratory failure 27.44 26.17 39 4560 215293 110369407
Mucosal inflammation 26.73 26.17 26 4573 96115 110488585

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J02AC05 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
Triazole and tetrazole derivatives
FDA CS M0002083 Azoles
FDA EPC N0000175487 Azole Antifungal
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000935 Antifungal Agents
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:71031 orphan drug
CHEBI has role CHEBI:75282 ergosterol biosynthesis inhibitor
CHEBI has role CHEBI:77884 EC 1.14.13.70 (sterol 14α-demethylase) inhibitor
CHEBI has role CHEBI:35718 antifungal agent
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

J02AC Triazole and tetrazole derivatives 5 drugs
fluconazoleitraconazoleoteseconazoleposaconazolevoriconazole

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

DiseaseRelationSNOMED_IDDOID
Cryptococcosis indication 42386007 DOID:12053
Aspergillosis indication 65553006 DOID:13564
Mucormycosis indication 76627001
Genetic short QT syndrome contraindication 698273002




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.43 acidic
pKa2 7.36 Basic
pKa3 2.98 Basic
pKa4 2.37 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL March 6, 2022 TREATMENT OF INVASIVE ASPERGILLOSIS
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL March 6, 2022 TREATMENT OF INVASIVE MUCORMYCOSIS IN PATIENTS 18 YEARS OF AGE AND OLDER
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL March 6, 2022 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS March 6, 2022 TREATMENT OF INVASIVE ASPERGILLOSIS
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS March 6, 2022 TREATMENT OF INVASIVE MUCORMYCOSIS IN PATIENTS 18 YEARS OF AGE AND OLDER
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL Sept. 6, 2022 PEDIATRIC EXCLUSIVITY
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL Sept. 6, 2022 PEDIATRIC EXCLUSIVITY
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS Sept. 6, 2022 PEDIATRIC EXCLUSIVITY
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL Dec. 8, 2026 NEW PATIENT POPULATION
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL Dec. 8, 2026 NEW PATIENT POPULATION
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS Dec. 8, 2026 NEW PATIENT POPULATION
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL June 8, 2027 PEDIATRIC EXCLUSIVITY
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL June 8, 2027 PEDIATRIC EXCLUSIVITY
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS June 8, 2027 PEDIATRIC EXCLUSIVITY
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL Sept. 6, 2027 GENERATING ANTIBIOTIC INCENTIVES NOW
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL Sept. 6, 2027 GENERATING ANTIBIOTIC INCENTIVES NOW
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS Sept. 6, 2027 GENERATING ANTIBIOTIC INCENTIVES NOW
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL Dec. 8, 2030 TREATMENT OF INVASIVE ASPERGILLOSIS IN PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WHO WEIGH 16 KILOGRAMS (KG) AND GREATER
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL Dec. 8, 2030 TREATMENT OF INVASIVE MUCORMYCOSIS IN PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WHO WEIGH 16 KG AND GREATER
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL Dec. 8, 2030 TREATMENT OF INVASIVE ASPERGILLOSIS IN PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WHO WEIGH 16 KILOGRAMS (KG) AND GREATER
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL Dec. 8, 2030 TREATMENT OF INVASIVE MUCORMYCOSIS IN PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WHO WEIGH 16 KG AND GREATER
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS Dec. 8, 2030 TREATMENT OF INVASIVE ASPERGILLOSIS IN PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS Dec. 8, 2030 TREATMENT OF INVASIVE MUCORMYCOSIS IN PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER
186MG CRESEMBA ASTELLAS N207500 March 6, 2015 RX CAPSULE ORAL June 8, 2031 PEDIATRIC EXCLUSIVITY
74.5MG CRESEMBA ASTELLAS N207500 Nov. 22, 2022 RX CAPSULE ORAL June 8, 2031 PEDIATRIC EXCLUSIVITY
372MG CRESEMBA ASTELLAS N207501 March 6, 2015 RX POWDER INTRAVENOUS June 8, 2031 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
ATP-binding cassette sub-family G member 2 Transporter IC50 4.96 CHEMBL

External reference:

IDSource
4034331 VANDF
QKM PDB_CHEM_ID
CHEMBL1183349 ChEMBL_ID
946075-13-4 SECONDARY_CAS_RN
497235-79-7 SECONDARY_CAS_RN
DB06636 DRUGBANK_ID
DB11633 DRUGBANK_ID
1608321 RXNORM
233407 MMSL
30943 MMSL
d08355 MMSL
015945 NDDF
015946 NDDF
724004002 SNOMEDCT_US
724005001 SNOMEDCT_US
724006000 SNOMEDCT_US
763601000 SNOMEDCT_US
765386003 SNOMEDCT_US
C4018471 UMLSCUI
C1832021 UMLSCUI
CHEBI:85977 CHEBI
CHEMBL3137333 ChEMBL_ID
CHEMBL409153 ChEMBL_ID
6918606 PUBCHEM_CID
241479-67-4 SECONDARY_CAS_RN
6918485 PUBCHEM_CID
VH2L779W8Q UNII
8784 INN_ID
8783 INN_ID
C508735 MESH_SUPPLEMENTAL_RECORD_UI
60UTO373KE UNII
CHEBI:85979 CHEBI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
CRESEMBA HUMAN PRESCRIPTION DRUG LABEL 1 0469-0420 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 40 mg INTRAVENOUS NDA 27 sections
CRESEMBA HUMAN PRESCRIPTION DRUG LABEL 1 0469-0520 CAPSULE 100 mg ORAL NDA 27 sections
CRESEMBA HUMAN PRESCRIPTION DRUG LABEL 1 0469-2860 CAPSULE 40 mg ORAL NDA 27 sections