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	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

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	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 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	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 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	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:

Source	Code	Description
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|

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	Type	Activity value (-log[M])	Bioact source
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN	IC50	5.50	CHEMBL
Uncharacterized oxidoreductase CzcO-like	Enzyme		CZCO_GEOKA			WOMBAT-PK
Cruzipain	Enzyme		CYSP_TRYCR	IC50	5.22	CHEMBL
Spike glycoprotein	Glycoprotein		SPIKE_SARS2	Kd	5.42	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