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

Stem definition	Drug id	CAS RN
	1497	54-85-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: isoniazid 4-Pyridinecarboxylic hydrazide armazid isoniazide isonicotinohydrazide	Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Molecular weight: 137.14 Formula: C6H7N3O CLOGP: -0.67 LIPINSKI: 0 HAC: 4 HDO: 2 TPSA: 68.01 ALOGS: -0.59 ROTB: 1 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

isoniazid
4-Pyridinecarboxylic hydrazide
armazid
isoniazide
isonicotinohydrazide

Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.

Molecular weight: 137.14
Formula: C6H7N3O
CLOGP: -0.67
LIPINSKI: 0
HAC: 4
HDO: 2
TPSA: 68.01
ALOGS: -0.59
ROTB: 1

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.30	g	O
0.30	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	153 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	7 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	72.92 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	80 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.82 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	7.40 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	1 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Sept. 29, 1952	FDA	SANDOZ

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
Drug reaction with eosinophilia and systemic symptoms	867.99	54.48	184	1790	5334	2350777
Acute hepatic failure	576.94	54.48	116	1858	2526	2353585
Drug-induced liver injury	521.07	54.48	113	1861	3586	2352525
Pyrexia	457.83	54.48	185	1789	53523	2302588
Drug resistance	447.91	54.48	94	1880	2530	2353581
Paradoxical drug reaction	432.25	54.48	70	1904	403	2355708
Jaundice	419.23	54.48	102	1872	5406	2350705
Hepatotoxicity	415.94	54.48	93	1881	3388	2352723
Hepatitis	355.65	54.48	92	1882	6245	2349866
Tuberculosis	276.74	54.48	60	1914	1875	2354236
Alanine aminotransferase increased	271.16	54.48	89	1885	13943	2342168
Aspartate aminotransferase increased	255.76	54.48	83	1891	12529	2343582
Vomiting	231.92	54.48	127	1847	71475	2284636
Tuberculoma of central nervous system	216.67	54.48	29	1945	24	2356087
Pulmonary tuberculosis	199.32	54.48	40	1934	845	2355266
Drug interaction	191.27	54.48	84	1890	29079	2327032
Exposure during pregnancy	179.52	54.48	77	1897	25142	2330969
Hepatic encephalopathy	175.54	54.48	40	1934	1567	2354544
Transaminases increased	173.99	54.48	49	1925	4538	2351573
Eosinophilia	165.57	54.48	43	1931	2927	2353184
Disseminated tuberculosis	160.73	54.48	31	1943	528	2355583
Nausea	154.04	54.48	116	1858	112073	2244038
Immune reconstitution inflammatory syndrome associated tuberculosis	153.06	54.48	21	1953	25	2356086
Lymphadenopathy	146.32	54.48	45	1929	5653	2350458
Hepatic failure	142.15	54.48	44	1930	5645	2350466
Hepatic function abnormal	139.18	54.48	44	1930	6048	2350063
Rash maculo-papular	136.91	54.48	40	1934	4212	2351899
Liver injury	136.22	54.48	35	1939	2279	2353832
Generalised tonic-clonic seizure	136.11	54.48	42	1932	5330	2350781
Encephalopathy	129.81	54.48	39	1935	4522	2351589
Hepatic enzyme increased	122.37	54.48	45	1929	9757	2346354
Toxicity to various agents	121.77	54.48	64	1910	32690	2323421
Coagulopathy	119.01	54.48	33	1941	2876	2353235
Liver function test abnormal	118.50	54.48	41	1933	7449	2348662
Condition aggravated	117.48	54.48	62	1912	31917	2324194
Pruritus	110.22	54.48	66	1908	43274	2312837
Rash	109.88	54.48	74	1900	59484	2296627
Hepatocellular injury	108.18	54.48	33	1941	4022	2352089
Cerebellar ataxia	108.10	54.48	19	1955	187	2355924
Seizure	94.20	54.48	49	1925	24417	2331694
Anaemia	93.62	54.48	55	1919	34737	2321374
Immune reconstitution inflammatory syndrome	88.97	54.48	22	1952	1222	2354889
Headache	88.07	54.48	73	1901	80106	2276005
Thrombocytopenia	84.32	54.48	42	1932	19089	2337022
Abdominal pain	83.77	54.48	51	1923	34323	2321788
Blood bilirubin increased	79.63	54.48	28	1946	5317	2350794
Meningitis tuberculous	77.40	54.48	13	1961	95	2356016
Neurotoxicity	77.24	54.48	22	1952	2108	2354003
Liver transplant	77.07	54.48	17	1957	570	2355541
Neuropathy peripheral	74.81	54.48	33	1941	11399	2344712
Metabolic acidosis	72.78	54.48	27	1947	5971	2350140
Liver disorder	71.02	54.48	27	1947	6387	2349724
Blood alkaline phosphatase increased	70.49	54.48	27	1947	6518	2349593
Tuberculosis of central nervous system	70.11	54.48	11	1963	49	2356062
Rhabdomyolysis	69.86	54.48	27	1947	6677	2349434
Gamma-glutamyltransferase increased	67.34	54.48	25	1949	5537	2350574
Intentional overdose	65.53	54.48	30	1944	11291	2344820
Peritoneal tuberculosis	62.31	54.48	11	1963	111	2356000
Cholestasis	61.22	54.48	21	1953	3700	2352411
Multiple-drug resistance	60.87	54.48	12	1962	229	2355882
Face oedema	60.00	54.48	21	1953	3927	2352184
Malaise	59.57	54.48	50	1924	55535	2300576
Drug ineffective	58.76	54.48	65	1909	101559	2254552
Maternal exposure during pregnancy	57.76	54.48	30	1944	14833	2341278
Abdominal pain upper	56.86	54.48	34	1940	22066	2334045
Pancreatitis acute	56.66	54.48	20	1954	3833	2352278
Glomerulonephritis minimal lesion	55.12	54.48	9	1965	54	2356057

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
Paradoxical drug reaction	846.08	47.91	137	2097	364	1744183
Drug-induced liver injury	832.89	47.91	181	2053	3056	1741491
Drug reaction with eosinophilia and systemic symptoms	659.60	47.91	163	2071	4907	1739640
Jaundice	655.25	47.91	168	2066	5894	1738653
Hepatotoxicity	581.49	47.91	134	2100	2950	1741597
Drug resistance	429.71	47.91	106	2128	3124	1741423
Tuberculosis	377.29	47.91	86	2148	1780	1742767
Pyrexia	359.54	47.91	181	2053	46219	1698328
Hepatitis	271.97	47.91	81	2153	4874	1739673
Hepatic failure	241.34	47.91	77	2157	5826	1738721
Tuberculoma of central nervous system	228.34	47.91	33	2201	23	1744524
Alanine aminotransferase increased	228.04	47.91	89	2145	12189	1732358
Liver function test abnormal	214.83	47.91	70	2164	5656	1738891
Immune reconstitution inflammatory syndrome	206.28	47.91	51	2183	1498	1743049
Immune system disorder	204.01	47.91	45	2189	790	1743757
Pulmonary tuberculosis	182.53	47.91	43	2191	1023	1743524
Hepatic function abnormal	173.70	47.91	63	2171	7011	1737536
Acute hepatic failure	168.66	47.91	46	2188	1997	1742550
Aspartate aminotransferase increased	164.91	47.91	68	2166	10688	1733859
Skin disorder	161.44	47.91	45	2189	2119	1742428
Vomiting	159.38	47.91	100	2134	38215	1706332
Hepatic enzyme increased	144.14	47.91	54	2180	6567	1737980
Condition aggravated	140.57	47.91	75	2159	21075	1723472
Meningitis tuberculous	131.63	47.91	22	2212	73	1744474
Nausea	119.80	47.91	94	2140	51102	1693445
Serpiginous choroiditis	119.11	47.91	16	2218	0	1744547
Rash maculo-papular	105.97	47.91	37	2197	3666	1740881
Drug interaction	101.12	47.91	67	2167	27891	1716656
Decreased appetite	100.60	47.91	63	2171	23808	1720739
Eosinophilia	99.99	47.91	35	2199	3492	1741055
Disseminated tuberculosis	98.77	47.91	23	2211	517	1744030
Metabolic acidosis	92.35	47.91	37	2197	5365	1739182
Encephalopathy	92.03	47.91	35	2199	4417	1740130
Hepatitis toxic	91.85	47.91	21	2213	434	1744113
Anaemia	90.86	47.91	64	2170	29393	1715154
Liver disorder	90.84	47.91	37	2197	5599	1738948
Blood bilirubin increased	90.72	47.91	38	2196	6172	1738375
Rash	90.16	47.91	71	2163	38622	1705925
Acute kidney injury	89.86	47.91	68	2166	34876	1709671
Hepatitis fulminant	87.39	47.91	22	2212	692	1743855
Liver injury	86.86	47.91	27	2207	1855	1742692
Transaminases increased	85.32	47.91	32	2202	3885	1740662
Hepatic encephalopathy	81.63	47.91	27	2207	2265	1742282
Lymphadenopathy	80.21	47.91	31	2203	4083	1740464
Hepatocellular injury	79.96	47.91	29	2205	3202	1741345
Neuropathy peripheral	79.18	47.91	39	2195	9214	1735333
Drug eruption	78.95	47.91	28	2206	2898	1741649
Coma	78.64	47.91	36	2198	7226	1737321
Optic neuritis	75.64	47.91	20	2214	766	1743781
Toxicity to various agents	75.47	47.91	57	2177	29084	1715463
Hydrocephalus	73.13	47.91	20	2214	872	1743675
Generalised tonic-clonic seizure	70.12	47.91	28	2206	4018	1740529
Immune reconstitution inflammatory syndrome associated tuberculosis	68.54	47.91	11	2223	26	1744521
Tubulointerstitial nephritis	67.45	47.91	25	2209	2933	1741614
Thrombocytopenia	67.34	47.91	47	2187	21202	1723345
Demodicidosis	66.55	47.91	10	2224	12	1744535
Multiple-drug resistance	66.29	47.91	15	2219	295	1744252
Pruritus	65.85	47.91	48	2186	23174	1721373
Bilirubin conjugated increased	57.32	47.91	15	2219	551	1743996
Seizure	55.09	47.91	41	2193	20400	1724147
Hepatic necrosis	53.32	47.91	15	2219	726	1743821
Peritoneal tuberculosis	51.73	47.91	10	2224	87	1744460
Rhabdomyolysis	50.96	47.91	31	2203	11059	1733488
Papule	50.90	47.91	14	2220	623	1743924
Blindness	50.69	47.91	20	2214	2776	1741771
Granuloma	48.84	47.91	13	2221	510	1744037
Tuberculous pleurisy	48.80	47.91	10	2224	120	1744427
Erythema	48.70	47.91	33	2201	14155	1730392

Pharmacologic Action:

Source	Code	Description
ATC	J04AC01	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Hydrazides
ATC	J04AC51	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Hydrazides
ATC	J04AM01	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM02	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM03	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM04	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM05	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM06	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM07	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
ATC	J04AM08	ANTIINFECTIVES FOR SYSTEMIC USE ANTIMYCOBACTERIALS DRUGS FOR TREATMENT OF TUBERCULOSIS Combinations of drugs for treatment of tuberculosis
CHEBI has role	CHEBI:88188	drug allergen
CHEBI has role	CHEBI:33231	antitubercular agent
FDA EPC	N0000175483	Antimycobacterial
MeSH PA	D000900	Anti-Bacterial Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000963	Antimetabolites
MeSH PA	D000995	Antitubercular Agents
MeSH PA	D054872	Fatty Acid Synthesis Inhibitors
MeSH PA	D000960	Hypolipidemic Agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Inactive tuberculosis	indication	11999007
Acute tuberculosis	indication	25629007
Pulmonary tuberculosis	indication	154283005	DOID:2957
Tuberculosis of meninges	off-label use	58437007
Atypical mycobacterial infection	off-label use	111812000
Nutritional disorder	contraindication	2492009	DOID:374
Alcoholism	contraindication	7200002
Jaundice	contraindication	18165001
Acute hepatitis	contraindication	37871000
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Diabetes mellitus	contraindication	73211009	DOID:9351
Gout	contraindication	90560007	DOID:13189
Anemia due to enzyme deficiency	contraindication	111577008
Acute hepatic failure	contraindication	197270009
Disease of liver	contraindication	235856003	DOID:409
Diabetic - poor control	contraindication	268519009
Peripheral nerve disease	contraindication	302226006
Porphyria	contraindication	418470004
Diabetic peripheral neuropathy	contraindication	424736006
Slow acetylator due to N-acetyltransferase enzyme variant	contraindication	425079005
Prolonged-Severe Nausea and Vomiting	contraindication
Chronic Hepatic Disease	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.98	acidic
pKa2	3.79	Basic
pKa3	1.94	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])	Bioact source	MoA source
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.31	WOMBAT-PK
Cytochrome P450 3A5	Enzyme	P20815	CP3A5_HUMAN		IC50	4.96	WOMBAT-PK
Enoyl-[acyl-carrier-protein] reductase [NADH]	Enzyme		INHA_MYCTU	INHIBITOR			WOMBAT-PK	CHEMBL
Catalase-peroxidase	Enzyme		KATG_MYCTO				WOMBAT-PK
Dihydrofolate reductase	Enzyme		DYR_MYCTU		Ki	9	CHEMBL

External reference:

ID	Source
D007538	MESH_DESCRIPTOR_UI
4017505	VUID
N0000145890	NUI
C0022209	UMLSCUI
D00346	KEGG_DRUG
81335000	SNOMEDCT_US
2955	MMSL
387472004	SNOMEDCT_US
4929	MMSL
d00101	MMSL
4017505	VANDF
6038	RXNORM
002844	NDDF
3767	PUBCHEM_CID
CHEBI:6030	CHEBI
CHEMBL64	ChEMBL_ID
DB00951	DRUGBANK_ID
V83O1VOZ8L	UNII
4188	INN_ID
ISZ	PDB_CHEM_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Rifamate	HUMAN PRESCRIPTION DRUG LABEL	2	0068-0509	CAPSULE	150 mg	ORAL	ANDA	13 sections
Rifater	HUMAN PRESCRIPTION DRUG LABEL	3	0088-0576	TABLET, SUGAR COATED	50 mg	ORAL	NDA	14 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0185-4350	TABLET	300 mg	ORAL	NDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0185-4351	TABLET	100 mg	ORAL	NDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0440-1655	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0440-7655	TABLET	300 mg	ORAL	ANDA	14 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0527-1109	TABLET	300 mg	ORAL	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0066	TABLET	100 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0071	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3056	INJECTION, SOLUTION	100 mg	INTRAMUSCULAR	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	10135-584	TABLET	300 mg	ORAL	ANDA	14 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	10544-087	TABLET	300 mg	ORAL	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	10544-121	TABLET	300 mg	ORAL	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	10544-218	TABLET	300 mg	ORAL	ANDA	14 sections
ISONIAZID	HUMAN PRESCRIPTION DRUG LABEL	1	16590-984	TABLET	300 mg	ORAL	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	21695-627	TABLET	300 mg	ORAL	ANDA	14 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	43063-463	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	46287-009	SOLUTION	50 mg	ORAL	ANDA	14 sections
isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	46672-597	SYRUP	50 mg	ORAL	ANDA	13 sections
isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	46672-865	TABLET	100 mg	ORAL	ANDA	13 sections
isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	46672-866	TABLET	300 mg	ORAL	ANDA	13 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	50090-0370	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	50090-0410	TABLET	100 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	51079-083	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	51655-391	TABLET	300 mg	ORAL	ANDA	10 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	52959-145	TABLET	300 mg	ORAL	ANDA	14 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	53002-2920	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	53808-1041	TABLET	300 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	54868-2304	TABLET	100 mg	ORAL	ANDA	12 sections
Isoniazid	HUMAN PRESCRIPTION DRUG LABEL	1	54868-2416	TABLET	300 mg	ORAL	ANDA	12 sections