clofazimine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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 Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 0.20 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 7.03 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 57 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.763 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.932 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.033 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 5.093 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.220 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.320 % High 1
herg hERG pIC50 5.455 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.581 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.710 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.520 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK5,CDK9,CHEK1,CSF1R,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK1,JAK2,JAK3,MAP2K6,MAP3K1,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKCD,PRKDC,SGK1,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ZAP70 65
kinase-selectivity-class ACVR2B,BRAF,ERBB2,SIK2,SIK3,ZAP70 6
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.489 High 1
mh-clint Mouse hepatocyte intrinsic clearance 14.521 High 1
mppb Mouse plasma protein binding (% unbound) 0.170 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.503 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.200 % High 1
rh-clint Rat hepatocyte intrinsic clearance 5.420 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.120 % High 1
rppb Rat plasma protein binding (% unbound) 0.230 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.393 uM High 1

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 702.20 24.64 254 7411 72202 90548580
Drug resistance 310.10 24.64 111 7554 30338 90590444
Neuropathy peripheral 168.21 24.64 118 7547 136852 90483930
Mycobacterium avium complex infection 145.65 24.64 39 7626 4059 90616723
Anaemia 141.35 24.64 161 7504 352641 90268141
Ototoxicity 126.11 24.64 30 7635 1934 90618848
Skin discolouration 113.13 24.64 61 7604 44254 90576528
Hepatotoxicity 97.59 24.64 56 7609 45786 90574996
Drug reaction with eosinophilia and systemic symptoms 93.07 24.64 53 7612 42705 90578077
Off label use 87.48 24.64 246 7419 1102006 89518776
Vomiting 84.23 24.64 197 7468 788096 89832686
Optic neuropathy 83.36 24.64 23 7642 2675 90618107
Haemoptysis 79.85 24.64 44 7621 33276 90587506
Polyneuropathy 73.92 24.64 35 7630 19306 90601476
Type 2 lepra reaction 72.30 24.64 11 7654 56 90620726
Mycobacterium abscessus infection 72.04 24.64 17 7648 1058 90619724
Skin hyperpigmentation 69.73 24.64 25 7640 6826 90613956
Tinnitus 69.34 24.64 44 7621 43058 90577724
Alanine aminotransferase increased 63.09 24.64 63 7602 118275 90502507
Aspartate aminotransferase increased 62.77 24.64 59 7606 102878 90517904
Cough 62.76 24.64 112 7553 368850 90251932
Respiratory failure 59.40 24.64 61 7604 118357 90502425
Deafness 54.67 24.64 30 7635 22484 90598298
Nausea 52.18 24.64 208 7457 1110108 89510674
Deafness neurosensory 51.46 24.64 20 7645 6821 90613961
Disseminated mycobacterium avium complex infection 50.78 24.64 10 7655 262 90620520
Transaminases increased 50.14 24.64 34 7631 37158 90583624
Product use in unapproved indication 49.54 24.64 96 7569 336140 90284642
Pathogen resistance 44.80 24.64 19 7646 8096 90612686
Myelosuppression 41.14 24.64 35 7630 53556 90567226
Antimicrobial susceptibility test intermediate 39.52 24.64 6 7659 30 90620752
Mycobacterial infection 38.14 24.64 12 7653 2198 90618584
Dyspnoea 38.05 24.64 161 7504 880794 89739988
Bronchiectasis 36.41 24.64 23 7642 22307 90598475
Pain 32.98 24.64 22 7643 996319 89624463
Optic neuritis 32.40 24.64 16 7649 9662 90611120
Herbal toxicity 32.02 24.64 5 7660 31 90620751
Meningitis tuberculous 31.81 24.64 8 7657 650 90620132
Hypoacusis 31.80 24.64 23 7642 27827 90592955
Incorrect product administration duration 29.27 24.64 19 7646 19303 90601479
Nephropathy toxic 28.32 24.64 16 7649 12672 90608110
Pyelonephritis chronic 28.18 24.64 6 7659 233 90620549
Cystic fibrosis 27.80 24.64 11 7654 3930 90616852
Cardiopulmonary failure 27.16 24.64 11 7654 4177 90616605
Concomitant disease aggravated 27.00 24.64 15 7650 11503 90609279
Paradoxical drug reaction 26.93 24.64 12 7653 5754 90615028
Drug-induced liver injury 25.96 24.64 35 7630 90283 90530499
Hypokalaemia 25.08 24.64 42 7623 131074 90489708
Immune reconstitution inflammatory syndrome 24.68 24.64 12 7653 7007 90613775
Atypical mycobacterial infection 24.65 24.64 8 7657 1618 90619164

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 805.16 22.52 311 7699 47634 42565691
Type 2 lepra reaction 254.85 22.52 46 7964 309 42613016
Drug resistance 203.66 22.52 108 7902 34140 42579185
Hepatotoxicity 183.28 22.52 91 7919 25076 42588249
Neuropathy peripheral 179.03 22.52 150 7860 101703 42511622
Off label use 97.95 22.52 301 7709 638034 41975291
Anaemia 93.65 22.52 179 7831 280099 42333226
Intentional product use issue 87.07 22.52 86 7924 71747 42541578
Deafness neurosensory 75.88 22.52 28 7982 3718 42609607
Drug-induced liver injury 74.64 22.52 60 7950 38213 42575112
Nausea 71.88 22.52 199 7811 396600 42216725
Ototoxicity 68.63 22.52 23 7987 2302 42611023
Skin hyperpigmentation 65.81 22.52 26 7984 4155 42609170
Toxic optic neuropathy 63.63 22.52 18 7992 1022 42612303
Optic neuropathy 63.02 22.52 22 7988 2490 42610835
Deafness 60.33 22.52 35 7975 13105 42600220
Tuberculosis 54.76 22.52 30 7980 10069 42603256
Pathogen resistance 53.90 22.52 31 7979 11419 42601906
Product use in unapproved indication 53.21 22.52 111 7899 184345 42428980
Optic neuritis 52.32 22.52 22 7988 4120 42609205
Type 1 lepra reaction 51.16 22.52 9 8001 51 42613274
Incorrect product administration duration 51.01 22.52 24 7986 5856 42607469
Vomiting 50.02 22.52 143 7867 289580 42323745
Psoas abscess 48.85 22.52 14 7996 833 42612492
HIV infection 45.06 22.52 15 7995 1470 42611855
Urinary tract inflammation 43.74 22.52 10 8000 238 42613087
Tinnitus 41.38 22.52 38 7972 28900 42584425
Preterm premature rupture of membranes 41.29 22.52 8 8002 82 42613243
Polyneuropathy 40.11 22.52 31 7979 18630 42594695
Drug reaction with eosinophilia and systemic symptoms 39.51 22.52 44 7966 42031 42571294
Mycobacterium avium complex infection 37.97 22.52 16 7994 3011 42610314
Acoustic neuroma 37.11 22.52 8 8002 144 42613181
Ichthyosis 36.85 22.52 8 8002 149 42613176
Hypoacusis 35.76 22.52 29 7981 18673 42594652
Hepatitis cholestatic 34.39 22.52 22 7988 9802 42603523
Aspartate aminotransferase increased 34.27 22.52 56 7954 77107 42536218
Mycobacterium haemophilum infection 33.06 22.52 9 8001 443 42612882
Conductive deafness 31.86 22.52 9 8001 508 42612817
Myelosuppression 29.20 22.52 37 7973 40424 42572901
Hypertriglyceridaemia 28.97 22.52 20 7990 10106 42603219
Benign soft tissue neoplasm 27.24 22.52 6 8004 120 42613205
Blood sodium decreased 26.25 22.52 24 7986 18138 42595187
Deafness unilateral 25.91 22.52 11 7999 2108 42611217
Cardiopulmonary failure 25.63 22.52 14 7996 4669 42608656
Mycobacterial peritonitis 25.34 22.52 6 8004 167 42613158
Autism spectrum disorder 25.31 22.52 12 7998 2976 42610349
Vestibular disorder 24.58 22.52 9 8001 1168 42612157
Mycobacterium abscessus infection 24.35 22.52 8 8002 752 42612573
Hepatitis toxic 23.88 22.52 11 7999 2556 42610769
Pulmonary tuberculosis 23.53 22.52 14 7996 5487 42607838
Disseminated tuberculosis 22.88 22.52 11 7999 2813 42610512
Oral candidiasis 22.72 22.52 20 7990 14385 42598940
Haemoptysis 22.54 22.52 35 7975 46132 42567193

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 1441.51 20.44 542 14263 108418 110466076
Neuropathy peripheral 385.37 20.44 260 14545 179017 110395477
Drug resistance 364.81 20.44 169 14636 56205 110518289
Type 2 lepra reaction 324.53 20.44 55 14750 360 110574134
Hepatotoxicity 267.14 20.44 142 14663 63258 110511236
Anaemia 231.67 20.44 323 14482 546763 110027731
Off label use 159.98 20.44 500 14305 1499685 109074809
Ototoxicity 149.18 20.44 44 14761 4087 110570407
Optic neuropathy 143.97 20.44 44 14761 4614 110569880
Drug reaction with eosinophilia and systemic symptoms 129.87 20.44 99 14706 81996 110492498
Skin hyperpigmentation 128.05 20.44 47 14758 8649 110565845
Polyneuropathy 118.89 20.44 66 14739 31946 110542548
Skin discolouration 111.96 20.44 74 14731 48972 110525522
Deafness 110.08 20.44 59 14746 26650 110547844
Vomiting 106.24 20.44 314 14491 910361 109664133
Drug-induced liver injury 104.66 20.44 103 14702 119964 110454530
Deafness neurosensory 98.78 20.44 40 14765 9579 110564915
Tinnitus 97.91 20.44 74 14731 60466 110514028
Aspartate aminotransferase increased 95.00 20.44 112 14693 159824 110414670
Pathogen resistance 92.94 20.44 46 14759 17626 110556868
Nausea 91.45 20.44 366 14439 1235324 109339170
Intentional product use issue 87.96 20.44 135 14670 247771 110326723
Toxic optic neuropathy 84.20 20.44 22 14783 1306 110573188
Optic neuritis 83.33 20.44 37 14768 11110 110563384
Product use in unapproved indication 80.69 20.44 182 14623 447195 110127299
Mycobacterium avium complex infection 80.05 20.44 30 14775 5847 110568647
Haemoptysis 79.10 20.44 70 14735 71284 110503210
Type 1 lepra reaction 78.86 20.44 13 14792 70 110574424
Incorrect product administration duration 78.12 20.44 43 14762 20455 110554039
Alanine aminotransferase increased 76.60 20.44 108 14697 183665 110390829
Hypoacusis 70.53 20.44 49 14756 35142 110539352
Myelosuppression 66.07 20.44 72 14733 94268 110480226
Respiratory failure 58.46 20.44 104 14701 215228 110359266
Tuberculosis 53.57 20.44 32 14773 17742 110556752
Transaminases increased 52.64 20.44 53 14752 63337 110511157
HIV infection 52.00 20.44 15 14790 1288 110573206
Meningitis tuberculous 47.84 20.44 14 14791 1264 110573230
Pain 47.80 20.44 35 14770 954920 109619574
Cough 44.18 20.44 149 14656 461492 110113002
Immune reconstitution inflammatory syndrome 43.24 20.44 27 14778 16199 110558295
Cardiopulmonary failure 42.82 20.44 21 14784 7882 110566612
Pulmonary tuberculosis 42.80 20.44 22 14783 9117 110565377
Ichthyosis 42.78 20.44 9 14796 205 110574289
Decreased appetite 42.42 20.44 150 14655 475696 110098798
Urinary tract inflammation 42.40 20.44 10 14795 388 110574106
Pneumothorax 41.87 20.44 36 14769 35249 110539245
Psoas abscess 41.40 20.44 13 14792 1489 110573005
Fall 40.68 20.44 15 14790 603467 109971027
Mycobacterium abscessus infection 39.78 20.44 13 14792 1693 110572801
Infusion related reaction 39.60 20.44 3 14802 381159 110193335
Conductive deafness 39.52 20.44 9 14796 299 110574195
Hepatitis toxic 39.01 20.44 18 14787 5903 110568591
Drug hypersensitivity 38.76 20.44 7 14798 454083 110120411
Hypokalaemia 37.09 20.44 78 14727 182370 110392124
Antimicrobial susceptibility test intermediate 36.77 20.44 6 14799 30 110574464
Mycobacterium haemophilum infection 36.53 20.44 10 14795 709 110573785
Hepatitis cholestatic 36.46 20.44 25 14780 17541 110556953
Disseminated mycobacterium avium complex infection 34.87 20.44 9 14796 509 110573985
Malnutrition 34.76 20.44 29 14776 27250 110547244
Autism spectrum disorder 34.21 20.44 12 14793 1936 110572558
Mycobacterial infection 34.10 20.44 15 14790 4402 110570092
Acoustic neuroma 33.93 20.44 8 14797 310 110574184
Atypical mycobacterial infection 33.86 20.44 13 14792 2705 110571789
Nasopharyngitis 33.82 20.44 6 14799 394355 110180139
Hypertriglyceridaemia 33.55 20.44 23 14782 16131 110558363
Treatment noncompliance 33.54 20.44 45 14760 72945 110501549
Concomitant disease aggravated 33.29 20.44 23 14782 16341 110558153
Pigmentation disorder 32.52 20.44 17 14788 7294 110567200
Psychotic disorder 32.42 20.44 37 14768 50900 110523594
Foetal growth restriction 32.40 20.44 13 14792 3037 110571457
Swelling 30.85 20.44 5 14800 351036 110223458
Rheumatoid arthritis 29.38 20.44 3 14802 299610 110274884
Benign soft tissue neoplasm 28.76 20.44 6 14799 131 110574363
Hepatitis 27.69 20.44 46 14759 90008 110484486
Vestibular disorder 27.21 20.44 11 14794 2621 110571873
Joint swelling 26.63 20.44 13 14792 442832 110131662
Blood sodium decreased 26.38 20.44 29 14776 38290 110536204
Infective pulmonary exacerbation of cystic fibrosis 25.98 20.44 19 14786 14752 110559742
Histiocytosis 25.87 20.44 5 14800 73 110574421
Mycobacterial peritonitis 25.34 20.44 6 14799 237 110574257
Nephropathy toxic 24.71 20.44 24 14781 27454 110547040
Immune reconstitution inflammatory syndrome associated tuberculosis 24.45 20.44 8 14797 1046 110573448
Pyelonephritis chronic 24.14 20.44 6 14799 291 110574203
Bronchiectasis 24.06 20.44 27 14778 36466 110538028
Chronic obstructive pulmonary disease 23.74 20.44 48 14757 109110 110465384
Facial paralysis 23.38 20.44 22 14783 24192 110550302
Herbal toxicity 23.24 20.44 4 14801 29 110574465
Weight increased 22.79 20.44 14 14791 419630 110154864
Bicytopenia 22.62 20.44 13 14792 6711 110567783
Tooth discolouration 22.43 20.44 8 14797 1355 110573139
Haemolytic anaemia 22.13 20.44 20 14785 20900 110553594
Electrolyte imbalance 22.06 20.44 26 14779 37002 110537492
Cor pulmonale 21.71 20.44 9 14796 2285 110572209
Preterm premature rupture of membranes 21.60 20.44 8 14797 1507 110572987
Dyspnoea 21.34 20.44 234 14571 1106638 109467856
Poor feeding infant 21.10 20.44 5 14800 198 110574296
Haemoglobin decreased 20.91 20.44 77 14728 248650 110325844

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
ATC J04BA51 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 drug
CHEBI has role CHEBI:35816 leprostatic drug
CHEBI has role CHEBI:37958 dye
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D007917 Leprostatic Agents

Related Drugs by ATC class:

J04BA Drugs for treatment of lepra 3 drugs
aldesulfonedapsonerifampicin

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




🐶 Veterinary Drug Use

None

🐶 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
ATP-binding cassette sub-family G member 2 Transporter IC50 5.50 CHEMBL
Uncharacterized oxidoreductase CzcO-like Enzyme WOMBAT-PK
Cruzipain Enzyme IC50 5.22 CHEMBL
Spike glycoprotein Glycoprotein Kd 5.42 CHEMBL

External reference:

IDSource
4019504 VUID
N0000147624 NUI
D00278 KEGG_DRUG
203021 RXNORM
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
4019504 VANDF

Pharmaceutical products:

None