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 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 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 508.26 26.46 188 4970 59342 63424522
Drug resistance 147.04 26.46 59 5099 22874 63460990
Neuropathy peripheral 109.02 26.46 83 5075 113584 63370280
Anaemia 98.69 26.46 120 5038 293310 63190554
Vomiting 85.53 26.46 158 5000 559459 62924405
Hepatotoxicity 85.37 26.46 47 5111 36994 63446870
Optic neuropathy 76.14 26.46 20 5138 2012 63481852
Off label use 72.88 26.46 165 4993 674297 62809567
Type 2 lepra reaction 70.33 26.46 10 5148 30 63483834
Polyneuropathy 64.98 26.46 29 5129 14560 63469304
Respiratory failure 61.50 26.46 57 5101 101801 63382063
Skin hyperpigmentation 55.07 26.46 20 5138 5901 63477963
Skin discolouration 53.31 26.46 35 5123 37793 63446071
Product use in unapproved indication 53.24 26.46 69 5089 179011 63304853
Aspartate aminotransferase increased 49.67 26.46 48 5110 90229 63393635
Drug reaction with eosinophilia and systemic symptoms 46.93 26.46 31 5127 33805 63450059
Haemoptysis 46.48 26.46 29 5129 28697 63455167
Ototoxicity 44.36 26.46 12 5146 1350 63482514
Intentional product use issue 43.93 26.46 53 5105 127839 63356025
Myelosuppression 38.52 26.46 24 5134 23679 63460185
Alanine aminotransferase increased 37.26 26.46 44 5114 103726 63380138
Meningitis tuberculous 32.95 26.46 8 5150 585 63483279
Pathogen resistance 32.65 26.46 14 5144 6384 63477480
Herbal toxicity 32.23 26.46 5 5153 31 63483833
Drug-induced liver injury 31.24 26.46 26 5132 40196 63443668
Cardiopulmonary failure 29.17 26.46 11 5147 3601 63480263
Dyspnoea 28.97 26.46 118 5040 661195 62822669
Mycobacterial infection 28.32 26.46 9 5149 1774 63482090
Pyelonephritis chronic 28.25 26.46 6 5152 240 63483624
Nausea 28.12 26.46 140 5018 854331 62629533
Transaminases increased 28.01 26.46 22 5136 31345 63452519
Pain 27.47 26.46 13 5145 740615 62743249
Cough 27.41 26.46 68 5090 292675 63191189

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 645.45 25.83 245 5547 40707 34910432
Type 2 lepra reaction 245.02 25.83 40 5752 155 34950984
Hepatotoxicity 185.65 25.83 84 5708 21401 34929738
Neuropathy peripheral 135.07 25.83 111 5681 83152 34867987
Drug resistance 113.48 25.83 64 5728 25863 34925276
Intentional product use issue 108.07 25.83 85 5707 59731 34891408
Off label use 102.63 25.83 218 5574 419306 34531833
Anaemia 73.28 25.83 135 5657 233200 34717939
Ototoxicity 71.59 25.83 22 5770 1895 34949244
Skin hyperpigmentation 67.61 25.83 24 5768 3240 34947899
Deafness 63.74 25.83 33 5759 11232 34939907
Incorrect product administration duration 58.56 25.83 24 5768 4787 34946352
Type 1 lepra reaction 55.94 25.83 9 5783 31 34951108
Nausea 53.04 25.83 149 5643 339759 34611380
Product use in unapproved indication 52.85 25.83 80 5712 117419 34833720
Tuberculosis 51.05 25.83 26 5766 8551 34942588
Polyneuropathy 49.99 25.83 31 5761 14865 34936274
Vomiting 47.14 25.83 117 5675 247504 34703635
Myelosuppression 45.03 25.83 32 5760 19233 34931906
Optic neuropathy 42.80 25.83 15 5777 1950 34949189
Aspartate aminotransferase increased 42.19 25.83 54 5738 67729 34883410
Drug-induced liver injury 39.56 25.83 35 5757 28797 34922342
Tinnitus 39.31 25.83 30 5762 20088 34931051
Acoustic neuroma 37.32 25.83 8 5784 160 34950979
Deafness neurosensory 37.26 25.83 15 5777 2856 34948283
HIV infection 36.12 25.83 12 5780 1327 34949812
Hypertriglyceridaemia 34.62 25.83 20 5772 8428 34942711
Optic neuritis 34.09 25.83 15 5777 3559 34947580
Toxic optic neuropathy 32.78 25.83 10 5782 840 34950299
Urinary tract inflammation 31.40 25.83 7 5785 169 34950970
Hepatitis cholestatic 30.42 25.83 18 5774 7929 34943210
Pathogen resistance 29.96 25.83 19 5773 9463 34941676
Blood sodium decreased 29.06 25.83 23 5769 16228 34934911
Hypoacusis 29 25.83 23 5769 16278 34934861
Benign soft tissue neoplasm 28.18 25.83 6 5786 116 34951023
Neuropsychiatric symptoms 28.04 25.83 9 5783 893 34950246
Conductive deafness 27.46 25.83 7 5785 303 34950836
Hepatitis toxic 26.44 25.83 11 5781 2276 34948863
Iridocyclitis 26.26 25.83 10 5782 1642 34949497
Vestibular disorder 26.23 25.83 9 5783 1098 34950041

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 1083.36 21.97 420 10421 89966 79643581
Type 2 lepra reaction 312.06 21.97 49 10792 179 79733368
Neuropathy peripheral 268.28 21.97 191 10650 141114 79592433
Hepatotoxicity 251.99 21.97 128 10713 51224 79682323
Drug resistance 218.14 21.97 109 10732 42104 79691443
Off label use 166.06 21.97 373 10468 906842 78826705
Anaemia 156.93 21.97 243 10598 444772 79288775
Intentional product use issue 137.68 21.97 134 10707 151978 79581569
Polyneuropathy 117.76 21.97 60 10781 24091 79709456
Optic neuropathy 116.12 21.97 35 10806 3449 79730098
Vomiting 110.51 21.97 264 10577 665564 79067983
Skin hyperpigmentation 108.91 21.97 40 10801 7263 79726284
Ototoxicity 101.04 21.97 31 10810 3243 79730304
Deafness 90.33 21.97 48 10793 20989 79712558
Drug-induced liver injury 84.91 21.97 71 10770 66046 79667501
Aspartate aminotransferase increased 84.36 21.97 99 10742 138542 79595005
Incorrect product administration duration 83.26 21.97 38 10803 11984 79721563
Product use in unapproved indication 82.76 21.97 133 10708 250226 79483321
Myelosuppression 79.77 21.97 56 10785 40240 79693307
Type 1 lepra reaction 75.74 21.97 12 10829 47 79733500
Skin discolouration 69.76 21.97 52 10789 40982 79692565
Nausea 61.12 21.97 274 10567 956922 78776625
Tinnitus 59.80 21.97 49 10792 44284 79689263
Optic neuritis 56.35 21.97 27 10814 9493 79724054
Respiratory failure 54.18 21.97 92 10749 180819 79552728
Drug reaction with eosinophilia and systemic symptoms 53.21 21.97 54 10787 64190 79669357
Tuberculosis 52.37 21.97 30 10811 15168 79718379
Haemoptysis 51.81 21.97 50 10791 55949 79677598
Alanine aminotransferase increased 51.78 21.97 85 10756 162485 79571062
Pathogen resistance 48.59 21.97 28 10813 14314 79719233
Meningitis tuberculous 48.45 21.97 14 10827 1191 79732356
Pain 46.24 21.97 19 10822 703783 79029764
HIV infection 44.89 21.97 13 10828 1114 79732433
Toxic optic neuropathy 44.60 21.97 13 10828 1140 79732407
Pulmonary tuberculosis 42.62 21.97 21 10820 7844 79725703
Deafness neurosensory 39.12 21.97 19 10822 6879 79726668
Hypertriglyceridaemia 38.24 21.97 23 10818 12717 79720830
Hypoacusis 37.90 21.97 32 10809 30118 79703429
Hypokalaemia 37.60 21.97 69 10772 143971 79589576
Fall 37.52 21.97 10 10831 487619 79245928
Psychotic disorder 36.48 21.97 36 10805 41366 79692181
Hepatitis toxic 34.79 21.97 16 10825 5131 79728416
Acoustic neuroma 33.99 21.97 8 10833 303 79733244
Decreased appetite 33.97 21.97 113 10728 342305 79391242
Cardiopulmonary failure 33.43 21.97 17 10824 6784 79726763
Pneumothorax 33.43 21.97 29 10812 28294 79705253
Transaminases increased 33.18 21.97 38 10803 51705 79681842
Conductive deafness 30.47 21.97 7 10834 238 79733309
Hepatitis cholestatic 29.15 21.97 20 10821 13832 79719715
Benign soft tissue neoplasm 28.89 21.97 6 10835 126 79733421
Treatment noncompliance 27.95 21.97 35 10806 52233 79681314
Vestibular disorder 27.79 21.97 11 10830 2444 79731103
Drug hypersensitivity 27.43 21.97 4 10837 298912 79434635
Bicytopenia 26.89 21.97 13 10828 4657 79728890
Mycobacterial infection 26.67 21.97 12 10829 3656 79729891
Malnutrition 26.48 21.97 23 10818 22479 79711068
Immune reconstitution inflammatory syndrome associated tuberculosis 26.15 21.97 8 10833 828 79732719
Infective pulmonary exacerbation of cystic fibrosis 25.74 21.97 18 10823 12833 79720714
Urinary tract inflammation 24.84 21.97 6 10835 254 79733293
Pyelonephritis chronic 24.17 21.97 6 10835 285 79733262
Blood sodium decreased 24.03 21.97 26 10815 33229 79700318
Electrolyte imbalance 23.82 21.97 25 10816 30856 79702691
Herbal toxicity 23.18 21.97 4 10837 29 79733518
Neuropsychiatric symptoms 22.02 21.97 8 10833 1407 79732140

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 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
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
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