thiamazole Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	1745	60-56-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: methimazole methylimidazolethiol thyrozol thymidazole thymidazol thycapzol thiamazole tapazole methymazol	A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Molecular weight: 114.17 Formula: C4H6N2S CLOGP: -0.34 LIPINSKI: 0 HAC: 2 HDO: 1 TPSA: 15.27 ALOGS: -1 ROTB: 0 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

methimazole
methylimidazolethiol
thyrozol
thymidazole
thymidazol
thycapzol
thiamazole
tapazole
methymazol

A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme.

Molecular weight: 114.17
Formula: C4H6N2S
CLOGP: -0.34
LIPINSKI: 0
HAC: 2
HDO: 1
TPSA: 15.27
ALOGS: -1
ROTB: 0

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
10	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	8.76 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Hosey CM, Chan R, Benet LZ
BA (Bioavailability)	93 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.86 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.70 mL/min/kg	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	2.40 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
June 21, 1950	FDA

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
Agranulocytosis	374.02	13.49	144	8465	22041	46655412
Hyperthyroidism	329.15	13.49	111	8498	11600	46665853
Thyrotoxic crisis	198.59	13.49	42	8567	703	46676750
Hypothyroidism	68.15	13.49	52	8557	31286	46646167
Choanal atresia	63.19	13.49	10	8599	26	46677427
Antithyroid arthritis syndrome	57.55	13.49	8	8601	4	46677449
Exophthalmos	53.47	13.49	16	8593	1129	46676324
Anti-neutrophil cytoplasmic antibody positive vasculitis	41.45	13.49	15	8594	1920	46675533
Toxic nodular goitre	38.68	13.49	6	8603	13	46677440
Goitre	38.27	13.49	19	8590	5312	46672141
Polyarthritis	37.39	13.49	20	8589	6522	46670931
Endocrine ophthalmopathy	32.37	13.49	8	8601	273	46677180
Dysmorphism	30.72	13.49	12	8597	1895	46675558
Pulmonary alveolar haemorrhage	30.37	13.49	15	8594	4147	46673306
Neuroglycopenia	26.29	13.49	5	8604	47	46677406
Oropharyngeal pain	26.01	13.49	48	8561	74120	46603333
Mucocutaneous candidiasis	26.00	13.49	4	8605	8	46677445
Kidney duplex	25.66	13.49	5	8604	54	46677399
Insulin autoimmune syndrome	25.42	13.49	5	8604	57	46677396
Drug-induced liver injury	25.04	13.49	27	8582	25341	46652112
Aplasia cutis congenita	24.53	13.49	5	8604	69	46677384
Rheumatoid arthritis	24.46	13.49	7	8602	240208	46437245
Renal infarct	24.38	13.49	9	8600	1218	46676235
Clinodactyly	22.74	13.49	5	8604	101	46677352
Hypoglycaemia	22.71	13.49	38	8571	54311	46623142
Blood thyroid stimulating hormone decreased	22.25	13.49	12	8597	3977	46673476
Neutropenia	21.88	13.49	67	8542	143137	46534316
Sopor	21.16	13.49	22	8587	19806	46657647
Eosinophilic pleural effusion	20.63	13.49	4	8605	42	46677411
Hypoaldosteronism	19.81	13.49	5	8604	186	46677267
Thyroid haemorrhage	19.64	13.49	4	8605	55	46677398
Toxic goitre	19.50	13.49	3	8606	6	46677447
Autoimmune neutropenia	19.25	13.49	4	8605	61	46677392
Ecthyma	18.98	13.49	5	8604	221	46677232
Hypersensitivity vasculitis	18.92	13.49	11	8598	4210	46673243
Symptom masked	18.27	13.49	6	8603	574	46676879
Atrial fibrillation	18.25	13.49	51	8558	103539	46573914
Pyrexia	18.09	13.49	118	8491	348684	46328769
Drug interaction	17.52	13.49	79	8530	203015	46474438
Jaundice cholestatic	17.14	13.49	11	8598	5018	46672435
Acute generalised exanthematous pustulosis	16.98	13.49	14	8595	9391	46668062
Stevens-Johnson syndrome	16.64	13.49	21	8588	23276	46654177
Microscopic polyangiitis	16.43	13.49	4	8605	128	46677325
Cardiac arrest	16.41	13.49	45	8564	90354	46587099
Metabolic function test abnormal	15.64	13.49	4	8605	157	46677296
Drug intolerance	15.49	13.49	4	8605	147045	46530408
Large for dates baby	15.44	13.49	5	8604	458	46676995
Thyroidectomy	15.39	13.49	6	8603	943	46676510
Respiratory syncytial virus infection	15.07	13.49	10	8599	4825	46672628
Spigelian hernia	14.96	13.49	3	8606	38	46677415
Tonsillitis	14.83	13.49	10	8599	4954	46672499
Haemoptysis	14.71	13.49	21	8588	26168	46651285
Hepatitis cholestatic	14.33	13.49	11	8598	6666	46670787
Febrile neutropenia	14.19	13.49	44	8565	94583	46582870
Kidney transplant rejection	14.02	13.49	9	8600	4109	46673344
Retinal vasculitis	13.61	13.49	5	8604	667	46676786

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
Hyperthyroidism	344.87	20.41	94	3246	8004	29941134
Thyrotoxic crisis	67.72	20.41	14	3326	354	29948784
Agranulocytosis	66.12	20.41	37	3303	21905	29927233
Thyrotoxic periodic paralysis	62.32	20.41	10	3330	55	29949083
Kounis syndrome	51.03	20.41	15	3325	1658	29947480
Hypothyroidism	49.93	20.41	27	3313	14936	29934202
Polymerase chain reaction	46.02	20.41	8	3332	76	29949062
Goitre	39.19	20.41	12	3328	1524	29947614
Urine leukocyte esterase positive	34.96	20.41	8	3332	328	29948810
Albumin urine present	33.77	20.41	8	3332	382	29948756
Haemoglobinuria	30.95	20.41	8	3332	548	29948590
Mouth swelling	30.46	20.41	10	3330	1589	29947549
Thyroiditis	30.28	20.41	10	3330	1619	29947519
Exomphalos	28.57	20.41	6	3334	164	29948974
Pericarditis fungal	28.10	20.41	6	3334	178	29948960
Tracheo-oesophageal fistula	27.92	20.41	7	3333	424	29948714
Respiratory tract haemorrhage	27.62	20.41	8	3332	839	29948299
Urine ketone body present	26.47	20.41	8	3332	971	29948167
Cholestatic liver injury	26.47	20.41	9	3331	1592	29947546
Glycosuria	24.17	20.41	8	3332	1303	29947835
Electrolyte imbalance	23.20	20.41	15	3325	11485	29937653
Autoimmune thyroiditis	21.96	20.41	7	3333	1013	29948125
Coagulation time shortened	21.82	20.41	5	3335	206	29948932

Pharmacologic Action:

Source	Code	Description
ATC	H03BB02	SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS THYROID THERAPY ANTITHYROID PREPARATIONS Sulfur-containing imidazole derivatives
ATC	H03BB52	SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS THYROID THERAPY ANTITHYROID PREPARATIONS Sulfur-containing imidazole derivatives
MeSH PA	D013956	Antithyroid Agents
MeSH PA	D006727	Hormone Antagonists
FDA MoA	N0000175917	Thyroid Hormone Synthesis Inhibitors
FDA EPC	N0000175918	Thyroid Hormone Synthesis Inhibitor
CHEBI has role	CHEBI:50671	antithyroid agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Hyperthyroidism	indication	34486009	DOID:7998
Thyrotoxic crisis	off-label use	29028009	DOID:12837
Agranulocytosis	contraindication	17182001	DOID:12987
Hypothyroidism	contraindication	40930008	DOID:1459
Factor II deficiency	contraindication	73975000
Leukopenia	contraindication	84828003	DOID:615
Pancytopenia	contraindication	127034005	DOID:12450
Liver function tests abnormal	contraindication	166603001
Drug-induced hepatitis	contraindication	235876009
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Bone marrow depression	contraindication	307762000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.7	acidic

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])	Bioact source	MoA source
Thyroid peroxidase	Enzyme	P07202	PERT_HUMAN	INHIBITOR	IC50	5.57	WOMBAT-PK	CHEMBL
Lactoperoxidase	Enzyme	P22079	PERL_HUMAN		IC50	4.93	CHEMBL
Dopamine beta-hydroxylase	Unclassified		DOPO_BOVIN		Ki	4.35	CHEMBL
Lactoperoxidase	Enzyme		PERL_BOVIN		IC50	5.08	CHEMBL

External reference:

ID	Source
4017434	VUID
N0000145822	NUI
D00401	KEGG_DRUG
4017434	VANDF
C0025644	UMLSCUI
CHEBI:50673	CHEBI
MMZ	PDB_CHEM_ID
CHEMBL1515	ChEMBL_ID
D008713	MESH_DESCRIPTOR_UI
DB00763	DRUGBANK_ID
6649	IUPHAR_LIGAND_ID
4198	INN_ID
554Z48XN5E	UNII
1349907	PUBCHEM_CID
224936	RXNORM
2293	MMSL
31962	MMSL
5073	MMSL
d00290	MMSL
002139	NDDF
37656002	SNOMEDCT_US
404864000	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0205	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0210	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	23155-070	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	23155-071	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	42254-008	TABLET	5 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	42254-009	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	49884-640	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	49884-641	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	50090-2366	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	50090-3334	TABLET	5 mg	ORAL	ANDA	20 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	51293-820	TABLET	5 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	51293-821	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	53808-0850	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	53808-0949	TABLET	10 mg	ORAL	ANDA	18 sections
METHIMAZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	53808-1044	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5135	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	54868-6071	TABLET	5 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	60429-380	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	60429-381	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	60687-357	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	60687-370	TABLET	10 mg	ORAL	ANDA	19 sections
TAPAZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	60793-104	TABLET	5 mg	ORAL	ANDA	21 sections
TAPAZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	60793-105	TABLET	10 mg	ORAL	ANDA	21 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-2026	TABLET	5 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-2027	TABLET	10 mg	ORAL	ANDA	18 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-2224	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-2225	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-6408	TABLET	10 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-8347	TABLET	5 mg	ORAL	ANDA	19 sections
Methimazole	HUMAN PRESCRIPTION DRUG LABEL	1	64980-260	TABLET	5 mg	ORAL	ANDA	19 sections