clofazimine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	692	2030-63-9

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.10	g	O

ADMET properties:

Property	Value	Reference
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 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	57 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
Dec. 15, 1986	FDA	NOVARTIS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Uncharacterized oxidoreductase CzcO-like	Enzyme		CZCO_GEOKA					WOMBAT-PK
Cruzipain	Enzyme		CYSP_TRYCR		IC50	5.22		CHEMBL

External reference:

ID	Source
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