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

Stem definitionDrug idCAS RN
antineoplastics; anthraquinone derivatives 1821 65271-80-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • mitoxantrone
  • mitoxantrone hydrochloride
  • dihydroxyanthraquinone
  • mitoxanthrone
  • mitozantrone
  • nimitoxantron
  • mitoxantrone dihydrochloride
  • mitoxantrone HCl
An anthracenedione-derived antineoplastic agent.
  • Molecular weight: 444.49
  • Formula: C22H28N4O6
  • CLOGP: 2.30
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 8
  • TPSA: 163.18
  • ALOGS: -2.78
  • ROTB: 12

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 7.50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 7 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.78 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 0 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 12 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 7.90 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.25 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 53 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 23, 1987 FDA

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 259.79 26.57 149 4988 94478 46586447
Acute myeloid leukaemia 248.15 26.57 85 5052 15693 46665232
Myelodysplastic syndrome 158.45 26.57 61 5076 15650 46665275
Second primary malignancy 117.32 26.57 39 5098 6545 46674380
Acute promyelocytic leukaemia 112.87 26.57 25 5112 896 46680029
Pancytopenia 105.85 26.57 82 5055 84976 46595949
Sepsis 101.80 26.57 98 5039 135916 46545009
Neutropenia 97.53 26.57 98 5039 143106 46537819
Leukaemia recurrent 83.81 26.57 21 5116 1288 46679637
Thrombocytopenia 77.75 26.57 82 5055 126499 46554426
Acute myeloid leukaemia recurrent 77.57 26.57 20 5117 1376 46679549
Haemophagocytic lymphohistiocytosis 72.13 26.57 29 5108 8313 46672612
Progressive multifocal leukoencephalopathy 66.71 26.57 30 5107 11316 46669609
Bone marrow failure 66.15 26.57 41 5096 29628 46651297
Acute lymphocytic leukaemia recurrent 65.09 26.57 19 5118 2076 46678849
Bronchopulmonary aspergillosis 64.61 26.57 26 5111 7470 46673455
Chronic hepatitis 56.66 26.57 14 5123 810 46680115
Febrile bone marrow aplasia 56.38 26.57 23 5114 6839 46674086
Product use in unapproved indication 52.74 26.57 57 5080 90216 46590709
Lower respiratory tract infection fungal 49.32 26.57 10 5127 232 46680693
Mucormycosis 46.56 26.57 15 5122 2277 46678648
Chloroma 45.29 26.57 9 5128 188 46680737
Haematotoxicity 42.88 26.57 19 5118 6914 46674011
Abdominal wall wound 41.55 26.57 7 5130 55 46680870
Streptococcal bacteraemia 41.14 26.57 12 5125 1307 46679618
Cardiac failure 40.70 26.57 47 5090 79901 46601024
B precursor type acute leukaemia 39.28 26.57 8 5129 190 46680735
Bone marrow infiltration 38.33 26.57 9 5128 419 46680506
Graft versus host disease 37.39 26.57 17 5120 6571 46674354
Hypogammaglobulinaemia 37.20 26.57 16 5121 5422 46675503
Myeloblast percentage decreased 36.35 26.57 6 5131 41 46680884
Refractory cytopenia with multilineage dysplasia 35.75 26.57 7 5130 135 46680790
Hepatitis E 33.10 26.57 10 5127 1229 46679696
Stenotrophomonas infection 30.46 26.57 10 5127 1610 46679315
Stem cell transplant 29.61 26.57 10 5127 1756 46679169
Diffuse large B-cell lymphoma 29.58 26.57 14 5123 5924 46675001
Bacterial sepsis 29.45 26.57 12 5125 3555 46677370
Colitis 27.99 26.57 27 5110 37320 46643605
Clostridium bacteraemia 27.77 26.57 6 5131 191 46680734
Aspergillus infection 27.60 26.57 14 5123 6876 46674049
Venoocclusive liver disease 27.42 26.57 12 5125 4239 46676686
Differentiation syndrome 27.14 26.57 8 5129 903 46680022

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
Febrile neutropenia 331.34 21.69 231 6134 106462 29839651
Acute myeloid leukaemia 182.91 21.69 85 6280 17921 29928192
Myelodysplastic syndrome 161.29 21.69 79 6286 18699 29927414
Neutropenia 100.96 21.69 130 6235 128410 29817703
Septic shock 83.37 21.69 84 6281 63523 29882590
Bone marrow failure 81.51 21.69 60 6305 29725 29916388
Mucormycosis 73.15 21.69 31 6334 5237 29940876
Acute lymphocytic leukaemia recurrent 70.28 21.69 25 6340 2642 29943471
Fungal infection 68.10 21.69 40 6325 13560 29932553
Bronchopulmonary aspergillosis 66.48 21.69 38 6327 12246 29933867
Second primary malignancy 64.43 21.69 30 6335 6326 29939787
Minimal residual disease 53.59 21.69 12 6353 228 29945885
Ameloblastoma 52.19 21.69 10 6355 84 29946029
Leukaemia recurrent 46.37 21.69 16 6349 1545 29944568
Aspiration bone marrow abnormal 44.53 21.69 9 6356 102 29946011
Hypertensive hydrocephalus 42.10 21.69 8 6357 64 29946049
High-grade B-cell lymphoma 40.92 21.69 9 6356 157 29945956
Neoplasm progression 37.71 21.69 31 6334 17992 29928121
Haematopoietic neoplasm 37.53 21.69 7 6358 50 29946063
Thrombocytopenia 36.50 21.69 86 6279 136958 29809155
Neoplasm recurrence 36.30 21.69 14 6351 1853 29944260
Aspergillus infection 35.88 21.69 24 6341 10190 29935923
Abscess fungal 35.53 21.69 8 6357 156 29945957
Cytogenetic abnormality 35.13 21.69 11 6354 783 29945330
Clostridium bacteraemia 33.54 21.69 7 6358 94 29946019
Cardiotoxicity 33.21 21.69 17 6348 4397 29941716
Multiple organ dysfunction syndrome 33.13 21.69 53 6312 63434 29882679
Pneumonia fungal 32.31 21.69 18 6347 5515 29940598
Product use in unapproved indication 31.15 21.69 56 6309 73637 29872476
Gallbladder adenocarcinoma 30.36 21.69 5 6360 15 29946098
Acute lymphocytic leukaemia 29.58 21.69 14 6351 3058 29943055
Venoocclusive liver disease 29.33 21.69 18 6347 6595 29939518
Bacteraemia 28.92 21.69 25 6340 15535 29930578
Mucosal inflammation 28.90 21.69 34 6331 30460 29915653
Klebsiella infection 28.66 21.69 18 6347 6869 29939244
Respiratory tract infection fungal 28.56 21.69 9 6356 654 29945459
Refractory anaemia with an excess of blasts 28.53 21.69 8 6357 388 29945725
Pancytopenia 27.83 21.69 58 6307 84994 29861119
Colitis 26.97 21.69 33 6332 30787 29915326
Enamel anomaly 26.84 21.69 6 6359 113 29946000
Klebsiella sepsis 26.84 21.69 11 6354 1706 29944407
Genotoxicity 26.77 21.69 5 6360 36 29946077
Cystitis haemorrhagic 26.40 21.69 15 6350 4772 29941341
Hyperammonaemic encephalopathy 26.08 21.69 11 6354 1833 29944280
Large granular lymphocytosis 25.75 21.69 6 6359 137 29945976
Disease progression 25.58 21.69 54 6311 79820 29866293
Sepsis 24.98 21.69 78 6287 146317 29799796
Progressive multifocal leukoencephalopathy 24.27 21.69 18 6347 8995 29937118
Fungaemia 24.07 21.69 11 6354 2220 29943893
Gene mutation 22.78 21.69 8 6357 813 29945300
Osteonecrosis 22.35 21.69 22 6343 16113 29930000
Cholangitis infective 21.98 21.69 6 6359 263 29945850
Drug resistance 21.70 21.69 24 6341 20109 29926004

Pharmacologic Action:

SourceCodeDescription
ATC L01DB07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES
Anthracyclines and related substances
FDA MoA N0000000176 Topoisomerase Inhibitors
FDA EPC N0000175609 Topoisomerase Inhibitor
MeSH PA D000700 Analgesics
MeSH PA D000970 Antineoplastic Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
MeSH PA D059005 Topoisomerase II Inhibitors
CHEBI has role CHEBI:23240 chromophores
CHEBI has role CHEBI:37958 dyes
CHEBI has role CHEBI:76924 plant metabolites
CHEBI has role CHEBI:35610 cytostatic

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Acute myeloid leukemia, disease indication 91861009
Relapsing remitting multiple sclerosis indication 426373005 DOID:2378
Metastatic Prostate Carcinoma indication
Follicular non-Hodgkin's lymphoma off-label use 308121000
Metastatic Breast Carcinoma off-label use
Progressive Diffuse Large B-Cell Lymphoma off-label use
Mycosis contraindication 3218000 DOID:1564
Viral disease contraindication 34014006 DOID:934
Chronic heart failure contraindication 48447003
Hepatic failure contraindication 59927004
Acute infectious disease contraindication 63171007
Leukopenia contraindication 84828003 DOID:615
Left heart failure contraindication 85232009
Bacterial infectious disease contraindication 87628006
Radiation oncology AND/OR radiotherapy contraindication 108290001
Acute disease of cardiovascular system contraindication 128487001
Seizure disorder contraindication 128613002
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.37 acidic
pKa2 10.7 acidic
pKa3 9.13 Basic
pKa4 8.52 Basic
pKa5 4.01 Basic
pKa6 1.49 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
DNA topoisomerase 2-alpha Enzyme INHIBITOR IC90 5.96 WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel Ki 5.53 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 5.31 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 5.73 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 6.74 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 7.11 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 7.05 DRUG MATRIX
Epidermal growth factor receptor Kinase IC50 5.27 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.90 DRUG MATRIX
Receptor tyrosine-protein kinase erbB-2 Kinase IC50 5.69 DRUG MATRIX
ATP-binding cassette sub-family G member 2 Transporter Kact 5.15 WOMBAT-PK
Multidrug resistance-associated protein 1 Transporter IC50 6.29 WOMBAT-PK
Canalicular multispecific organic anion transporter 1 Transporter WOMBAT-PK
Multidrug resistance protein 1 Transporter IC50 5.84 WOMBAT-PK
Solute carrier family 22 member 3 Transporter IC50 4.22 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.36 CHEMBL
Solute carrier family 22 member 2 Transporter IC50 4.13 CHEMBL
Tyrosine-protein kinase BTK Kinase IC50 6 CHEMBL
Serine/threonine-protein kinase pim-1 Kinase IC50 7.29 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 6.28 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 6.72 CHEMBL
DNA-3-methyladenine glycosylase Enzyme IC50 5.60 CHEMBL
Arachidonate 15-lipoxygenase Enzyme IC50 5.75 DRUG MATRIX
Integrase Enzyme IC50 5.42 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1A Unclassified AC50 5.02 CHEMBL

External reference:

IDSource
4019842 VUID
N0000147929 NUI
D02166 KEGG_DRUG
70476-82-3 SECONDARY_CAS_RN
4019527 VANDF
4019842 VANDF
C0026259 UMLSCUI
CHEBI:37484 CHEBI
MIX PDB_CHEM_ID
CHEMBL58 ChEMBL_ID
CHEMBL1417019 ChEMBL_ID
CHEMBL1200827 ChEMBL_ID
D008942 MESH_DESCRIPTOR_UI
DB01204 DRUGBANK_ID
4212 PUBCHEM_CID
7242 IUPHAR_LIGAND_ID
4922 INN_ID
BZ114NVM5P UNII
203129 RXNORM
5124 MMSL
81184 MMSL
d00306 MMSL
002676 NDDF
004828 NDDF
108791001 SNOMEDCT_US
386913001 SNOMEDCT_US
412249002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4680 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 24 sections
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4685 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 24 sections
mitoXANTRONE HUMAN PRESCRIPTION DRUG LABEL 1 0703-4686 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 24 sections
Mitoxantrone HUMAN PRESCRIPTION DRUG LABEL 1 61703-343 INJECTION, SOLUTION, CONCENTRATE 2 mg INTRAVENOUS ANDA 28 sections
Mitoxantrone HUMAN PRESCRIPTION DRUG LABEL 1 63323-132 INJECTION, SOLUTION 2 mg INTRAVENOUS ANDA 15 sections