posaconazole Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
systemic antifungal agents, miconazole derivatives 3483 171228-49-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • posaconazole
  • noxafil
  • posaconazol
  • SCH 56592
  • SCH-56592
an antifungal medicine that belongs to the triazole group, it works by preventing the formation of ergosterol, which is an important part of fungal cell walls
  • Molecular weight: 700.79
  • Formula: C37H42F2N8O4
  • CLOGP: 4.11
  • LIPINSKI: 2
  • HAC: 12
  • HDO: 1
  • TPSA: 111.79
  • ALOGS: -4.77
  • ROTB: 12

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O
0.30 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.00 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 16.31 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 96 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 3.80 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 4.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 10.60 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 23, 2020 PMDA MSD K.K.
April 26, 2019 EMA Accord Healthcare S.L.U.
Sept. 15, 2006 FDA SCHERING

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
Febrile neutropenia 247.98 21.23 169 7669 94458 46583766
Mucormycosis 118.83 21.23 34 7804 2258 46675966
Bronchopulmonary aspergillosis 117.34 21.23 45 7793 7451 46670773
Hepatocellular injury 112.67 21.23 67 7771 29455 46648769
Pseudoaldosteronism 109.26 21.23 16 7822 22 46678202
Cholestasis 105.15 21.23 62 7776 26831 46651393
Acute myeloid leukaemia 102.64 21.23 51 7787 15727 46662497
Graft versus host disease 94.06 21.23 37 7801 6551 46671673
Graft versus host disease in gastrointestinal tract 93.74 21.23 29 7809 2521 46675703
Drug interaction 92.56 21.23 140 7698 202954 46475270
Fusarium infection 86.69 21.23 20 7818 558 46677666
Aspergillus infection 85.57 21.23 35 7803 6855 46671369
Neutropenia 72.77 21.23 104 7734 143100 46535124
Antibiotic level below therapeutic 72.54 21.23 11 7827 22 46678202
Product use in unapproved indication 66.85 21.23 79 7759 90194 46588030
Adenoviral hepatitis 66.58 21.23 14 7824 251 46677973
Septic shock 66.53 21.23 64 7774 57829 46620395
Acute myeloid leukaemia recurrent 60.40 21.23 18 7820 1378 46676846
Bicytopenia 57.28 21.23 18 7820 1646 46676578
Scedosporium infection 57.02 21.23 14 7824 512 46677712
Cytomegalovirus infection 56.02 21.23 36 7802 18108 46660116
Multiple organ dysfunction syndrome 55.36 21.23 55 7783 51655 46626569
Bone marrow failure 54.76 21.23 43 7795 29626 46648598
Gastrointestinal toxicity 50.38 21.23 21 7817 4310 46673914
Sinoatrial block 46.30 21.23 13 7825 805 46677419
Fungaemia 46.25 21.23 16 7822 1975 46676249
Sepsis 45.89 21.23 82 7756 135932 46542292
Pneumonia fungal 44.48 21.23 19 7819 4141 46674083
Fungal infection 40.40 21.23 36 7802 29484 46648740
Leukaemia recurrent 40.27 21.23 13 7825 1296 46676928
Venoocclusive liver disease 37.63 21.23 17 7821 4234 46673990
Venous haemorrhage 36.23 21.23 8 7830 182 46678042
Differentiation syndrome 36.19 21.23 11 7827 900 46677324
Blood bilirubin increased 35.90 21.23 36 7802 34148 46644076
Hyperbilirubinaemia 35.44 21.23 22 7816 10416 46667808
Acute kidney injury 35.32 21.23 103 7735 235752 46442472
Coagulation test abnormal 34.89 21.23 10 7828 667 46677557
Thrombocytopenia 34.85 21.23 70 7768 126511 46551713
Staphylococcal sepsis 33.77 21.23 19 7819 7513 46670711
Pancytopenia 33.55 21.23 55 7783 85003 46593221
Myelosuppression 33.37 21.23 19 7819 7684 46670540
Arthralgia 33.26 21.23 10 7828 364593 46313631
Electrocardiogram QT prolonged 33.21 21.23 42 7796 51283 46626941
Torsade de pointes 32.38 21.23 22 7816 12132 46666092
Cholecystitis acute 31.07 21.23 18 7820 7520 46670704
Hepatic necrosis 30.30 21.23 16 7822 5585 46672639
Pelvic venous thrombosis 30.13 21.23 11 7827 1586 46676638
Seroconversion test positive 29.68 21.23 5 7833 24 46678200
Enterococcal infection 29.64 21.23 17 7821 6970 46671254
Long QT syndrome 29.45 21.23 13 7825 3067 46675157
Hepatic failure 29.37 21.23 32 7806 33384 46644840
Graft versus host disease in skin 29.30 21.23 12 7826 2355 46675869
Enterobacter test positive 29.03 21.23 7 7831 237 46677987
Enterococcal bacteraemia 29.02 21.23 10 7828 1219 46677005
Geotrichum infection 29.00 21.23 8 7830 464 46677760
Systemic mycosis 27.66 21.23 9 7829 920 46677304
Hepatotoxicity 27.48 21.23 27 7811 24982 46653242
Acute lymphocytic leukaemia 27.47 21.23 12 7826 2761 46675463
Adenovirus infection 27.23 21.23 12 7826 2818 46675406
Acute lymphocytic leukaemia recurrent 27.23 21.23 11 7827 2084 46676140
Growth failure 27.02 21.23 7 7831 319 46677905
Partial seizures with secondary generalisation 26.97 21.23 7 7831 321 46677903
Fatigue 26.87 21.23 38 7800 608659 46069565
Graft versus host disease in lung 26.85 21.23 7 7831 327 46677897
Atrioventricular block second degree 26.84 21.23 13 7825 3786 46674438
Respiratory failure 26.76 21.23 53 7785 94763 46583461
Off label use 26.65 21.23 130 7708 379711 46298513
Renal tubular acidosis 26.55 21.23 10 7828 1573 46676651
Kussmaul respiration 26.52 21.23 6 7832 153 46678071
Pyrexia 26.36 21.23 122 7716 348680 46329544
Disseminated intravascular coagulation 25.65 21.23 23 7815 18982 46659242
Pain in extremity 25.64 21.23 6 7832 258674 46419550
Neurotoxicity 25.55 21.23 20 7818 13697 46664527
Endophthalmitis 25.54 21.23 12 7826 3266 46674958
Bacteraemia 24.97 21.23 20 7818 14159 46664065
Klebsiella sepsis 24.50 21.23 9 7829 1320 46676904
Transaminases increased 23.38 21.23 26 7812 27735 46650489
Acquired apparent mineralocorticoid excess 23.08 21.23 3 7835 0 46678224
Pain 21.79 21.23 29 7809 476919 46201305
Drug hypersensitivity 21.65 21.23 7 7831 243818 46434406
Systemic candida 21.30 21.23 10 7828 2717 46675507

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
Mucormycosis 193.65 19.15 72 10456 5196 29936754
Aspergillus infection 169.07 19.15 79 10449 10135 29931815
Febrile neutropenia 152.03 19.15 187 10341 106506 29835444
Bronchopulmonary aspergillosis 149.41 19.15 77 10451 12207 29929743
Product use in unapproved indication 145.42 19.15 153 10375 73540 29868410
Microsporidia infection 123.75 19.15 31 10497 573 29941377
Fusarium infection 115.27 19.15 33 10495 1031 29940919
Antibiotic level below therapeutic 107.17 19.15 18 10510 31 29941919
Septic shock 104.45 19.15 120 10408 63487 29878463
Pathogen resistance 91.65 19.15 49 10479 8361 29933589
Graft versus host disease 85.68 19.15 50 10478 10100 29931850
Drug resistance 84.17 19.15 64 10464 20069 29921881
Drug interaction 82.63 19.15 202 10326 199366 29742584
Cerebral aspergillosis 82.47 19.15 27 10501 1331 29940619
Pseudoaldosteronism 76.74 19.15 12 10516 9 29941941
Demodicidosis 74.99 19.15 16 10512 139 29941811
Fungal infection 69.91 19.15 49 10479 13551 29928399
Pneumonia fungal 68.15 19.15 35 10493 5498 29936452
Scedosporium infection 67.81 19.15 20 10508 695 29941255
Acute myeloid leukaemia recurrent 67.39 19.15 24 10504 1528 29940422
Acute myeloid leukaemia 66.07 19.15 53 10475 17953 29923997
Acanthamoeba infection 65.98 19.15 18 10510 469 29941481
Drug ineffective 65.59 19.15 264 10264 340123 29601827
Pseudomonas infection 63.97 19.15 42 10486 10440 29931510
Myositis 61.92 19.15 41 10487 10336 29931614
Neutropenia 59.45 19.15 136 10392 128404 29813546
Off label use 59.26 19.15 207 10321 249083 29692867
Enterococcal infection 57.74 19.15 36 10492 8188 29933762
Device related infection 47.87 19.15 43 10485 16972 29924978
Cytokine release syndrome 46.92 19.15 34 10494 9899 29932051
Systemic mycosis 46.06 19.15 17 10511 1199 29940751
Multiple organ dysfunction syndrome 45.90 19.15 81 10447 63406 29878544
Graft versus host disease in skin 43.88 19.15 22 10506 3285 29938665
Eye infection fungal 43.79 19.15 12 10516 318 29941632
Polymyositis 43.31 19.15 17 10511 1419 29940531
Fatigue 40.73 19.15 32 10496 320641 29621309
Candida infection 39.66 19.15 37 10491 15325 29926625
Nephropathy toxic 36.24 19.15 30 10498 10609 29931341
Brain herniation 35.78 19.15 20 10508 3720 29938230
Parainfluenzae virus infection 34.43 19.15 16 10512 2022 29939928
Cytomegalovirus infection 34.37 19.15 42 10486 23632 29918318
Skin necrosis 33.95 19.15 21 10507 4706 29937244
Retinal ischaemia 33.51 19.15 10 10518 362 29941588
Septic embolus 32.70 19.15 13 10515 1122 29940828
Neurotoxicity 32.59 19.15 31 10497 13151 29928799
Sepsis 31.60 19.15 118 10410 146277 29795673
Cardioactive drug level increased 31.25 19.15 14 10514 1625 29940325
Geotrichum infection 31.00 19.15 10 10518 470 29941480
Necrotising retinitis 30.68 19.15 11 10517 714 29941236
Neutropenic colitis 30.07 19.15 15 10513 2215 29939735
Hypokalaemia 29.95 19.15 59 10469 50133 29891817
Acanthamoeba keratitis 29.56 19.15 7 10521 101 29941849
Intracranial mass 28.79 19.15 12 10516 1169 29940781
Central nervous system lesion 28.33 19.15 19 10509 4887 29937063
Neutrophil Pelger-Huet anomaly present 28.25 19.15 8 10520 240 29941710
Pyrexia 28.05 19.15 188 10340 294301 29647649
Incorrect product formulation administered 27.15 19.15 5 10523 18 29941932
Lymphopenia 27.06 19.15 28 10500 13135 29928815
Fungal skin infection 26.01 19.15 14 10514 2418 29939532
Ileus paralytic 25.91 19.15 19 10509 5629 29936321
Fall 25.87 19.15 16 10512 181856 29760094
Phaeohyphomycosis 25.78 19.15 10 10518 808 29941142
Folliculitis 25.71 19.15 16 10512 3624 29938326
Differentiation syndrome 25.66 19.15 11 10517 1149 29940801
Viral haemorrhagic cystitis 25.29 19.15 10 10518 851 29941099
Brain compression 25.28 19.15 7 10521 193 29941757
Polyomavirus-associated nephropathy 25.06 19.15 15 10513 3170 29938780
Treatment failure 24.72 19.15 44 10484 34635 29907315
Cerebral artery embolism 24.71 19.15 10 10518 904 29941046
Systemic candida 24.33 19.15 14 10514 2750 29939200
Pain 23.45 19.15 16 10512 172625 29769325
Renal tubular disorder 23.33 19.15 17 10511 4989 29936961
Graft versus host disease in gastrointestinal tract 22.97 19.15 14 10514 3055 29938895
Inappropriate antidiuretic hormone secretion 22.95 19.15 24 10504 11398 29930552
Hyperbilirubinaemia 22.89 19.15 29 10499 16913 29925037
Myocardial infarction 22.55 19.15 8 10520 125617 29816333
Drug ineffective for unapproved indication 22.11 19.15 23 10505 10857 29931093
Brain abscess 22.07 19.15 13 10515 2668 29939282
Malaise 21.98 19.15 16 10512 166946 29775004
Nocardiosis 21.45 19.15 14 10514 3441 29938509
Gastrointestinal wall thinning 21.38 19.15 4 10524 16 29941934
Ecthyma 21.38 19.15 7 10521 345 29941605
Thrombotic microangiopathy 20.81 19.15 20 10508 8590 29933360
Graft versus host disease in liver 20.52 19.15 9 10519 993 29940957
Dizziness 20.50 19.15 23 10505 194886 29747064
Necrotising ulcerative gingivostomatitis 20.13 19.15 5 10523 89 29941861
Acquired apparent mineralocorticoid excess 20.04 19.15 4 10524 24 29941926
Encephalopathy 19.37 19.15 38 10490 32167 29909783

Pharmacologic Action:

SourceCodeDescription
ATC J02AC04 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
ANTIMYCOTICS FOR SYSTEMIC USE
Triazole derivatives
FDA CS M0002083 Azoles
MeSH PA D058888 14-alpha Demethylase Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000935 Antifungal Agents
MeSH PA D000977 Antiparasitic Agents
MeSH PA D000981 Antiprotozoal Agents
MeSH PA D065607 Cytochrome P-450 Enzyme Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006727 Hormone Antagonists
MeSH PA D065606 Metabolic Side Effects of Drugs and Substances
MeSH PA D065088 Steroid Synthesis Inhibitors
MeSH PA D014344 Trypanocidal Agents
FDA EPC N0000175487 Azole Antifungal
CHEBI has role CHEBI:36335 trypanosomicidal agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Mycosis indication 3218000 DOID:1564
Coccidioidomycosis indication 60826002 DOID:13450
Fusarium infection indication 64250002
Aspergillosis indication 65553006 DOID:13564
Candidiasis indication 78048006 DOID:1508
Chromoblastomycosis indication 187079000
Mycetoma indication 410039003 DOID:13078

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.68 acidic
pKa2 5.12 Basic
pKa3 5.0 Basic
pKa4 2.66 Basic
pKa5 0.3 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cytochrome P450 3A4 Enzyme WOMBAT-PK
Lanosterol 14-alpha demethylase Enzyme INHIBITOR MIC 9.40 WOMBAT-PK CHEMBL
14-alpha sterol demethylase Enzyme Kd 7.14 CHEMBL
14-alpha sterol demethylase Cyp51A Enzyme Kd 5.57 CHEMBL

External reference:

IDSource
4025699 VUID
N0000179745 NUI
D02555 KEGG_DRUG
4025699 VANDF
C1174778 UMLSCUI
CHEBI:64355 CHEBI
X2N PDB_CHEM_ID
CHEMBL1397 ChEMBL_ID
DB01263 DRUGBANK_ID
C101425 MESH_SUPPLEMENTAL_RECORD_UI
11428 IUPHAR_LIGAND_ID
7713 INN_ID
6TK1G07BHZ UNII
468595 PUBCHEM_CID
282446 RXNORM
21768 MMSL
320488 MMSL
83903 MMSL
d05853 MMSL
011210 NDDF
420282006 SNOMEDCT_US
421747003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NOXAFIL HUMAN PRESCRIPTION DRUG LABEL 1 0085-1328 SUSPENSION 40 mg ORAL NDA 31 sections
NOXAFIL HUMAN PRESCRIPTION DRUG LABEL 1 0085-2224 POWDER, FOR SUSPENSION 300 mg ORAL NDA 31 sections
NOXAFIL HUMAN PRESCRIPTION DRUG LABEL 1 0085-4324 TABLET, COATED 100 mg ORAL NDA 31 sections
NOXAFIL HUMAN PRESCRIPTION DRUG LABEL 1 0085-4331 SOLUTION 18 mg INTRAVENOUS NDA 31 sections
POSACONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 0254-2045 TABLET, COATED 100 mg ORAL NDA authorized generic 31 sections
POSACONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 0527-2133 TABLET, DELAYED RELEASE 100 mg ORAL ANDA 28 sections
POSACONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 16714-156 TABLET, DELAYED RELEASE 100 mg ORAL ANDA 28 sections
Posaconazole HUMAN PRESCRIPTION DRUG LABEL 1 60687-523 TABLET, DELAYED RELEASE 100 mg ORAL ANDA 29 sections
POSACONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 63629-2236 TABLET, COATED 100 mg ORAL NDA authorized generic 30 sections
POSACONULLZOLE HUMAN PRESCRIPTION DRUG LABEL 1 70748-258 TABLET, DELAYED RELEASE 100 mg ORAL ANDA 25 sections