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 463.91 28.31 172 4423 54416 56233056
Drug resistance 125.10 28.31 51 4544 20491 56266981
Neuropathy peripheral 102.52 28.31 77 4518 102816 56184656
Anaemia 93.84 28.31 112 4483 267399 56020073
Hepatotoxicity 89.93 28.31 46 4549 31107 56256365
Tuberculosis 79.71 28.31 31 4564 10998 56276474
Vomiting 76.09 28.31 141 4454 498087 55789385
Off label use 72.26 28.31 147 4448 556033 55731439
Optic neuropathy 71.96 28.31 19 4576 1941 56285531
Type 2 lepra reaction 70.04 28.31 10 4585 31 56287441
Skin hyperpigmentation 56.79 28.31 20 4575 5377 56282095
Mycobacterial infection 55.15 28.31 15 4580 1715 56285757
Polyneuropathy 55.02 28.31 25 4570 13025 56274447
Skin discolouration 53.75 28.31 34 4561 34322 56253150
Respiratory failure 52.99 28.31 51 4544 95011 56192461
Intentional product use issue 52.78 28.31 52 4543 99681 56187791
Drug reaction with eosinophilia and systemic symptoms 47.42 28.31 30 4565 30274 56257198
Myelosuppression 45.26 28.31 24 4571 17431 56270041
Product use in unapproved indication 44.38 28.31 56 4539 140766 56146706
Aspartate aminotransferase increased 43.56 28.31 43 4552 82559 56204913
Pulmonary tuberculosis 37.43 28.31 14 4581 4462 56283010
Alanine aminotransferase increased 33.95 28.31 40 4555 93622 56193850
Haemoptysis 33.53 28.31 23 4572 26537 56260935
Meningitis tuberculous 33.37 28.31 8 4587 552 56286920
Herbal toxicity 32.20 28.31 5 4590 31 56287441
Ototoxicity 32.05 28.31 9 4586 1157 56286315
Mycobacterium abscessus infection 31.88 28.31 8 4587 668 56286804
Drug-induced liver injury 30.31 28.31 24 4571 34438 56253034
Pathogen resistance 30.13 28.31 13 4582 5987 56281485
Tinnitus 28.76 28.31 22 4573 30020 56257452
Pyelonephritis chronic 28.32 28.31 6 4589 236 56287236

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 575.02 26.77 220 4974 37767 31654383
Type 2 lepra reaction 273.43 26.77 48 5146 316 31691834
Tuberculosis 207.35 26.77 70 5124 8271 31683879
Hepatotoxicity 189.42 26.77 82 5112 19044 31673106
Neuropathy peripheral 126.15 26.77 102 5092 75547 31616603
Intentional product use issue 123.62 26.77 85 5109 49262 31642888
Off label use 105.20 26.77 196 4998 347078 31345072
Anaemia 68.65 26.77 124 5070 213398 31478752
Deafness 66.40 26.77 33 5161 10432 31681718
Ototoxicity 65.13 26.77 20 5174 1738 31690412
Drug resistance 64.83 26.77 43 5151 23410 31668740
Skin hyperpigmentation 62.37 26.77 22 5172 2949 31689201
Incorrect product administration duration 61.42 26.77 24 5170 4278 31687872
Type 1 lepra reaction 56.04 26.77 9 5185 31 31692119
Vomiting 49.09 26.77 111 5083 223862 31468288
Product use in unapproved indication 47.29 26.77 69 5125 99102 31593048
Nausea 42.20 26.77 128 5066 307819 31384331
Tinnitus 40.57 26.77 28 5166 16247 31675903
Optic neuropathy 40.41 26.77 14 5180 1779 31690371
Aspartate aminotransferase increased 39.53 26.77 50 5144 62669 31629481
Acoustic neuroma 37.55 26.77 8 5186 157 31691993
Drug-induced liver injury 36.60 26.77 31 5163 24332 31667818
Hypertriglyceridaemia 36.32 26.77 20 5174 7778 31684372
Lepromatous leprosy 36.08 26.77 7 5187 84 31692066
Myelosuppression 35.62 26.77 25 5169 14895 31677255
Optic neuritis 35.27 26.77 15 5179 3315 31688835
Deafness neurosensory 34.74 26.77 14 5180 2702 31689448
HIV infection 34.01 26.77 12 5182 1608 31690542
Polyneuropathy 33.86 26.77 23 5171 12999 31679151
Pulmonary tuberculosis 33.30 26.77 16 5178 4695 31687455
Blood sodium decreased 30.50 26.77 23 5171 15292 31676858
Toxic optic neuropathy 29.22 26.77 9 5185 789 31691361
Oral candidiasis 27.46 26.77 19 5175 11058 31681092
Mycobacterium abscessus infection 27.19 26.77 8 5186 600 31691550
Iridocyclitis 27.06 26.77 10 5184 1530 31690620

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 964.29 21.52 379 9385 83138 70835542
Type 2 lepra reaction 338.51 21.52 57 9707 346 70918334
Hepatotoxicity 260.21 21.52 125 9639 43861 70874819
Neuropathy peripheral 254.00 21.52 178 9586 126718 70791962
Tuberculosis 208.40 21.52 78 9686 14770 70903910
Drug resistance 179.84 21.52 93 9671 38097 70880583
Off label use 167.53 21.52 335 9429 742725 70175955
Intentional product use issue 161.50 21.52 133 9631 120009 70798671
Anaemia 148.24 21.52 226 9538 403197 70515483
Optic neuropathy 109.60 21.52 33 9731 3200 70915480
Skin hyperpigmentation 104.21 21.52 38 9726 6677 70912003
Vomiting 103.92 21.52 242 9522 592869 70325811
Deafness 93.67 21.52 48 9716 19255 70899425
Polyneuropathy 88.98 21.52 48 9716 21367 70897313
Incorrect product administration duration 83.40 21.52 37 9727 10787 70907893
Ototoxicity 82.66 21.52 26 9738 2915 70915765
Myelosuppression 76.22 21.52 49 9715 30096 70888584
Type 1 lepra reaction 75.59 21.52 12 9752 47 70918633
Product use in unapproved indication 75.53 21.52 116 9648 207362 70711318
Aspartate aminotransferase increased 75.24 21.52 90 9674 126888 70791792
Skin discolouration 69.01 21.52 50 9714 37275 70881405
Tinnitus 63.57 21.52 47 9717 36129 70882551
Pulmonary tuberculosis 61.03 21.52 27 9737 7818 70910862
Mycobacterial infection 58.84 21.52 21 9743 3467 70915213
Optic neuritis 57.76 21.52 27 9737 8873 70909807
Drug-induced liver injury 56.90 21.52 53 9711 56060 70862620
Drug reaction with eosinophilia and systemic symptoms 55.40 21.52 53 9711 57960 70860720
Mycobacterium abscessus infection 51.71 21.52 15 9749 1277 70917403
Meningitis tuberculous 48.37 21.52 14 9750 1183 70917497
Lepromatous leprosy 48.35 21.52 9 9755 103 70918577
Alanine aminotransferase increased 46.12 21.52 77 9687 147403 70771277
Respiratory failure 46.11 21.52 83 9681 168652 70750028
Nausea 45.61 21.52 234 9530 851854 70066826
HIV infection 41.80 21.52 13 9751 1404 70917276
Toxic optic neuropathy 40.57 21.52 12 9752 1094 70917586
Pain 40.54 21.52 18 9746 628798 70289882
Hypokalaemia 40.35 21.52 68 9696 131120 70787560
Psychotic disorder 38.96 21.52 36 9728 37665 70881015
Haemoptysis 38.13 21.52 41 9723 51411 70867269
Hypertriglyceridaemia 36.96 21.52 22 9742 11789 70906891
Deafness neurosensory 36.59 21.52 18 9746 6614 70912066
Fall 35.03 21.52 9 9755 444087 70474593
Acoustic neuroma 34.56 21.52 8 9756 278 70918402
Pneumothorax 33.35 21.52 28 9736 25818 70892862
Hypoacusis 32.05 21.52 28 9736 27241 70891439
Treatment noncompliance 30.86 21.52 35 9729 46539 70872141
Bicytopenia 28.57 21.52 13 9751 4015 70914665
Cardiopulmonary failure 28.39 21.52 15 9749 6395 70912285
Malnutrition 28.28 21.52 23 9741 20294 70898386
Vestibular disorder 28.26 21.52 11 9753 2309 70916371
Transaminases increased 27.26 21.52 33 9731 46985 70871695
Decreased appetite 27.26 21.52 98 9666 304682 70613998
Electrolyte imbalance 26.50 21.52 25 9739 26836 70891844
Infective pulmonary exacerbation of cystic fibrosis 26.44 21.52 18 9746 12140 70906540
Blood sodium decreased 25.28 21.52 26 9738 30972 70887708
Oral candidiasis 24.19 21.52 23 9741 24929 70893751
Pyelonephritis chronic 24.18 21.52 6 9758 281 70918399
Tuberculoid leprosy 23.67 21.52 5 9759 113 70918567
Drug hypersensitivity 23.38 21.52 4 9760 262455 70656225
Steroid dependence 23.15 21.52 7 9757 688 70917992
Herbal toxicity 23.13 21.52 4 9760 29 70918651
Pathogen resistance 22.75 21.52 17 9747 13262 70905418
Poor feeding infant 22.67 21.52 5 9759 139 70918541
Hypomagnesaemia 22.64 21.52 28 9736 40736 70877944
Facial paralysis 22.59 21.52 20 9744 19788 70898892
Immune reconstitution inflammatory syndrome associated tuberculosis 21.92 21.52 7 9757 823 70917857

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 | Suggest Off label Use Form| |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