clofazimine ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
692 2030-63-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lamprene
  • clofazimine
  • chlofazimine
A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619)
  • Molecular weight: 473.40
  • Formula: C27H22Cl2N4
  • CLOGP: 7.55
  • LIPINSKI: 1
  • HAC: 4
  • HDO: 1
  • TPSA: 39.99
  • ALOGS: -5.50
  • ROTB: 4

  • Status: OFM

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

Drug dosage:

DoseUnitRoute
0.10 g O

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) 0.20 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 7.03 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 57 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
Dec. 15, 1986 FDA NOVARTIS

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
Electrocardiogram QT prolonged 399.88 27.85 153 4057 51733 50549181
Drug resistance 117.71 27.85 48 4162 18941 50581973
Neuropathy peripheral 98.74 27.85 74 4136 96683 50504231
Anaemia 85.83 27.85 105 4105 252351 50348563
Hepatotoxicity 83.10 27.85 42 4168 27184 50573730
Vomiting 78.31 27.85 138 4072 460620 50140294
Optic neuropathy 74.36 27.85 19 4191 1675 50599239
Off label use 74.11 27.85 137 4073 474289 50126625
Type 2 lepra reaction 71.43 27.85 10 4200 25 50600889
Intentional product use issue 59.42 27.85 50 4160 76868 50524046
Skin hyperpigmentation 56.87 27.85 20 4190 5256 50595658
Polyneuropathy 53.13 27.85 24 4186 12107 50588807
Respiratory failure 50.20 27.85 49 4161 91132 50509782
Drug reaction with eosinophilia and systemic symptoms 48.67 27.85 30 4180 28394 50572520
Skin discolouration 47.20 27.85 31 4179 32726 50568188
Myelosuppression 44.60 27.85 22 4188 13495 50587419
Product use in unapproved indication 43.83 27.85 51 4159 115768 50485146
Aspartate aminotransferase increased 39.37 27.85 40 4170 77958 50522956
Drug-induced liver injury 34.29 27.85 24 4186 28071 50572843
Haemoptysis 33.93 27.85 23 4187 25550 50575364
Meningitis tuberculous 33.53 27.85 8 4202 531 50600383
Herbal toxicity 32.11 27.85 5 4205 31 50600883
Alanine aminotransferase increased 30.25 27.85 37 4173 88322 50512592
Mycobacterial infection 29.09 27.85 9 4201 1587 50599327
Pyelonephritis chronic 28.70 27.85 6 4204 217 50600697

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
Electrocardiogram QT prolonged 535.82 25.55 206 4627 35931 29533763
Type 2 lepra reaction 248.14 25.55 40 4793 143 29569551
Hepatotoxicity 171.91 25.55 75 4758 17792 29551902
Intentional product use issue 127.97 25.55 82 4751 42416 29527278
Neuropathy peripheral 119.17 25.55 96 4737 70931 29498763
Off label use 103.27 25.55 179 4654 300621 29269073
Deafness 64.75 25.55 32 4801 10023 29559671
Skin hyperpigmentation 63.22 25.55 22 4811 2842 29566852
Incorrect product administration duration 62.95 25.55 24 4809 4017 29565677
Anaemia 58.91 25.55 112 4721 200839 29368855
Ototoxicity 58.86 25.55 18 4815 1547 29568147
Type 1 lepra reaction 56.06 25.55 9 4824 31 29569663
Vomiting 48.77 25.55 107 4726 212153 29357541
Product use in unapproved indication 45.32 25.55 63 4770 86812 29482882
Optic neuropathy 40.90 25.55 14 4819 1721 29567973
Tuberculosis 40.75 25.55 21 4812 7175 29562519
Nausea 40.57 25.55 121 4712 289134 29280560
Drug resistance 40.04 25.55 31 4802 21509 29548185
Tinnitus 39.31 25.55 27 4806 15587 29554107
Acoustic neuroma 38.18 25.55 8 4825 145 29569549
HIV infection 37.77 25.55 12 4821 1169 29568525
Drug-induced liver injury 37.73 25.55 30 4803 21625 29548069
Hypertriglyceridaemia 37.17 25.55 20 4813 7455 29562239
Aspartate aminotransferase increased 36.78 25.55 47 4786 59678 29510016
Polyneuropathy 35.37 25.55 23 4810 12129 29557565
Myelosuppression 35.24 25.55 23 4810 12204 29557490
Deafness neurosensory 32.02 25.55 13 4820 2565 29567129
Blood sodium decreased 31.31 25.55 23 4810 14744 29554950
Toxic optic neuropathy 29.91 25.55 9 4824 732 29568962
Optic neuritis 29.67 25.55 13 4820 3096 29566598
Iridocyclitis 27.74 25.55 10 4823 1430 29568264
Vestibular disorder 26.79 25.55 9 4824 1045 29568649
Oral candidiasis 25.71 25.55 18 4815 10704 29558990

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
Electrocardiogram QT prolonged 863.00 22.66 347 8716 79101 64410568
Type 2 lepra reaction 314.49 22.66 49 9014 161 64489508
Neuropathy peripheral 241.85 22.66 169 8894 117356 64372313
Hepatotoxicity 235.49 22.66 114 8949 39848 64449821
Intentional product use issue 175.00 22.66 128 8935 95236 64394433
Off label use 167.54 22.66 309 8754 632497 63857172
Drug resistance 145.35 22.66 79 8984 35023 64454646
Anaemia 132.88 22.66 210 8853 378470 64111199
Optic neuropathy 111.25 22.66 33 9030 2978 64486691
Vomiting 105.83 22.66 236 8827 550881 63938788
Skin hyperpigmentation 104.37 22.66 38 9025 6513 64483156
Deafness 89.21 22.66 46 9017 18313 64471356
Polyneuropathy 88.55 22.66 47 9016 19847 64469822
Incorrect product administration duration 83.08 22.66 36 9027 9722 64479947
Type 1 lepra reaction 77.57 22.66 12 9051 37 64489632
Product use in unapproved indication 76.03 22.66 108 8955 176510 64313159
Myelosuppression 75.36 22.66 45 9018 23785 64465884
Ototoxicity 71.62 22.66 23 9040 2700 64486969
Aspartate aminotransferase increased 68.12 22.66 84 8979 119704 64369965
Skin discolouration 63.80 22.66 47 9016 35208 64454461
Drug-induced liver injury 61.41 22.66 52 9011 47591 64442078
Tinnitus 60.63 22.66 45 9018 34088 64455581
Drug reaction with eosinophilia and systemic symptoms 57.54 22.66 53 9010 54164 64435505
HIV infection 46.24 22.66 13 9050 969 64488700
Respiratory failure 45.06 22.66 81 8982 161102 64328567
Meningitis tuberculous 44.65 22.66 13 9050 1098 64488571
Alanine aminotransferase increased 44.25 22.66 74 8989 138957 64350712
Nausea 42.75 22.66 220 8843 785580 63704089
Tuberculosis 42.20 22.66 25 9038 13013 64476656
Toxic optic neuropathy 42.16 22.66 12 9051 935 64488734
Psychotic disorder 41.01 22.66 36 9027 34542 64455127
Pulmonary tuberculosis 40.60 22.66 20 9043 7224 64482445
Hypokalaemia 40.29 22.66 66 8997 121837 64367832
Optic neuritis 38.45 22.66 20 9043 8096 64481573
Hypertriglyceridaemia 37.61 22.66 22 9041 11183 64478486
Haemoptysis 37.29 22.66 40 9023 49008 64440661
Acoustic neuroma 35.89 22.66 8 9055 229 64489440
Pain 35.13 22.66 17 9046 553494 63936175
Pneumothorax 34.37 22.66 28 9035 24270 64465399
Deafness neurosensory 33.95 22.66 17 9046 6357 64483312
Fall 32.85 22.66 9 9054 416817 64072852
Treatment noncompliance 32.25 22.66 35 9028 43447 64446222
Hypoacusis 30.81 22.66 27 9036 25840 64463829
Bicytopenia 29.64 22.66 13 9050 3609 64486060
Decreased appetite 27.13 22.66 94 8969 281195 64208474
Infective pulmonary exacerbation of cystic fibrosis 26.60 22.66 18 9045 11778 64477891
Transaminases increased 26.48 22.66 32 9031 44562 64445107
Blood sodium decreased 25.93 22.66 26 9037 29456 64460213
Cardiopulmonary failure 25.82 22.66 14 9049 6156 64483513
Mycobacterial infection 25.35 22.66 11 9052 2977 64486692
Malnutrition 24.88 22.66 21 9042 19104 64470565
Vestibular disorder 24.68 22.66 10 9053 2283 64487386
Pyelonephritis chronic 24.47 22.66 6 9057 262 64489407
Herbal toxicity 23.05 22.66 4 9059 29 64489640
Facial paralysis 22.99 22.66 20 9043 18946 64470723

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J04BA01 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF LEPRA
Drugs for treatment of lepra
FDA EPC N0000175483 Antimycobacterial
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory agent
CHEBI has role CHEBI:35816 leprostatic drugs
CHEBI has role CHEBI:37958 dyes
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D007917 Leprostatic Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Pyoderma gangrenosum indication 74578003 DOID:8553
Leprosy indication 81004002 DOID:1024
Erythema nodosum leprosum indication 240411003
Multibacillary leprosy indication 416257001
Dapsone resistant leprosy indication 416597004
Mycobacteriosis off-label use 88415009
Nausea and vomiting contraindication 16932000
Splenic infarction contraindication 22996003 DOID:2533
Disorder of digestive system contraindication 53619000 DOID:77
Diarrhea contraindication 62315008
Gastrointestinal hemorrhage contraindication 74474003
Gastrointestinal obstruction contraindication 126765001
Disease of liver contraindication 235856003 DOID:409
Breastfeeding (mother) contraindication 413712001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.81 Basic
pKa2 5.53 Basic
pKa3 2.07 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
Uncharacterized oxidoreductase CzcO-like Enzyme WOMBAT-PK
Cruzipain Enzyme IC50 5.22 CHEMBL

External reference:

IDSource
4019504 VUID
N0000147624 NUI
D00278 KEGG_DRUG
203021 RXNORM
4019504 VANDF
C0008996 UMLSCUI
CHEBI:3749 CHEBI
CHEMBL1292 ChEMBL_ID
D002991 MESH_DESCRIPTOR_UI
DB00845 DRUGBANK_ID
9184 IUPHAR_LIGAND_ID
2248 INN_ID
D959AE5USF UNII
2794 PUBCHEM_CID
1685 MMSL
4473 MMSL
d01121 MMSL
003007 NDDF
387410004 SNOMEDCT_US
72924009 SNOMEDCT_US

Pharmaceutical products:

None