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

Stem definition	Drug id	CAS RN
diuretics, chlorothiazide derivatives	1385	58-93-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: hydrochlorothiazide hydrochlorothiazid hydrochlorthiazide hydrochlorzide	A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Molecular weight: 297.73 Formula: C7H8ClN3O4S2 CLOGP: -0.36 LIPINSKI: 0 HAC: 7 HDO: 3 TPSA: 118.36 ALOGS: -2.12 ROTB: 1 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

hydrochlorothiazide
hydrochlorothiazid
hydrochlorthiazide
hydrochlorzide

A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.

Molecular weight: 297.73
Formula: C7H8ClN3O4S2
CLOGP: -0.36
LIPINSKI: 0
HAC: 7
HDO: 3
TPSA: 118.36
ALOGS: -2.12
ROTB: 1

Status: OFP

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

Drug dosage:

Dose	Unit	Route
25	mg	O
25	mg	O

ADMET properties:

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Property	Value	Reference
BA (Bioavailability)	71 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	11.18 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
EoM (Fraction excreted unchanged in urine)	100 %	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.72 mg/mL	Bocci G, Oprea TI, Benet LZ
fu (Fraction unbound in plasma)	0.56 %	Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

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Approvals:

Date	Agency	Company	Orphan
Feb. 12, 1959	FDA

FDA Adverse Event Reporting System (Female)

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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
Hyponatraemia	1225.56	9.85	1786	236089	110114	63141033
Pemphigus	616.93	9.85	15	237860	183711	63067436
Maternal exposure during pregnancy	538.52	9.85	89	237786	219973	63031174
Hypokalaemia	529.96	9.85	1189	236686	102615	63148532
Hand deformity	487.51	9.85	27	237848	159430	63091717
Systemic lupus erythematosus	469.81	9.85	104	237771	208814	63042333
Glossodynia	445.09	9.85	69	237806	178807	63072340
Contraindicated product administered	345.16	9.85	193	237682	217455	63033692
Synovitis	322.93	9.85	148	237727	186770	63064377
Off label use	321.10	9.85	1370	236505	673092	62578055

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FDA Adverse Event Reporting System (Male)

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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
Hyponatraemia	458.54	10.35	974	128948	81717	34745292
Angioedema	394.36	10.35	584	129338	36790	34790219
Off label use	295.07	10.35	708	129214	418816	34408193
Hypokalaemia	251.83	10.35	622	129300	57592	34769417
Drug abuse	216.86	10.35	51	129871	99045	34727964
Acute kidney injury	216.68	10.35	1899	128023	303089	34523920
Dizziness	165.00	10.35	1380	128542	217141	34609868
Syncope	155.66	10.35	713	129209	90738	34736271
Cerebrovascular accident	150.90	10.35	670	129252	84141	34742868
Death	150.57	10.35	867	129055	397182	34429827

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FDA Adverse Event Reporting System (Geriatric)

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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
Hyponatraemia	1535.28	9.75	2512	289652	175336	79276888
Hypokalaemia	677.86	9.75	1576	290588	142464	79309760
Angioedema	537.18	9.75	984	291180	75051	79377173
Acute kidney injury	471.89	9.75	3386	288778	516018	78936206
Off label use	463.93	9.75	1737	290427	905478	78546746
Drug abuse	332.59	9.75	92	292072	162599	79289625
Cerebrovascular accident	319.58	9.75	1270	290894	154022	79298202
Myocardial infarction	312.45	9.75	1420	290744	182709	79269515
Maternal exposure during pregnancy	307.04	9.75	63	292101	136475	79315749
Hand deformity	293.40	9.75	23	292141	103896	79348328

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FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

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Source	Code	Description
ATC	C03AA03	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, plain
ATC	C03AB03	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides and potassium in combination
ATC	C03AX01	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, combinations with other drugs
ATC	C03EA01	CARDIOVASCULAR SYSTEM DIURETICS DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION Low-ceiling diuretics and potassium-sparing agents
ATC	C09BX03	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ACE INHIBITORS, COMBINATIONS ACE inhibitors, other combinations
ATC	C09DX01	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations
ATC	C09DX03	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations
ATC	C09DX06	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations
ATC	C09DX07	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations
ATC	C09DX08	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations

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Drug Use | Suggest Off label Use Form| |View source of the data|

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Disease	Relation	SNOMED_ID	DOID
Hypertensive disorder	indication	38341003	DOID:10763
Chronic heart failure	indication	48447003
Edema	indication	267038008
Hypertensive urgency	indication	443482000
Pulmonary Edema due to Chronic Heart Failure	indication
Peripheral Edema due to Chronic Heart Failure	indication
Edema due to Hepatic Cirrhosis	indication
Hypertension with Left Ventricular Hypertrophy	indication
Edema due to Nephrotic Syndrome	indication
Nephrogenic diabetes insipidus	off-label use	111395007	DOID:12387

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🐶 Veterinary Drug Use

Species	Use	Relation
Cattle	Postparturient udder edema	Indication

🐶 Veterinary products

Product	Applicant	Ingredients
Hydrozide Injection	Boehringer lngelheim Animal Health USA Inc.	1

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.89	acidic
pKa2	11.02	acidic
pKa3	0.71	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Solute carrier family 12 member 3	Transporter	P55017	S12A3_HUMAN	INHIBITOR	A2	7.01	WOMBAT-PK	CHEMBL
Carbonic anhydrase 1	Enzyme	P00915	CAH1_HUMAN		Ki	6.48	CHEMBL
Carbonic anhydrase 4	Enzyme	P22748	CAH4_HUMAN				WOMBAT-PK
Calcium-activated potassium channel subunit alpha-1	Ion channel	Q12791	KCMA1_HUMAN				WOMBAT-PK
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN		Ki	5.90	WOMBAT-PK
Astrosclerin-3	Enzyme		A6YCJ1_9METZ		Ki	6.40	CHEMBL
Delta carbonic anhydrase	Unclassified		Q5U9J1_THAWE		Ki	5.37	CHEMBL
Carbonic anhydrase	Enzyme		Q5TU56_ANOGA		Ki	7.50	CHEMBL
Carbonic anhydrase, alpha family	Unclassified		Q31FD6_HYDCU		Ki	6.53	CHEMBL
Carbonate dehydratase	Enzyme		B2V8E3_SULSY		Ki	8.14	CHEMBL

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External reference:

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ID	Source
002294	NDDF
0J48LPH2TH	UNII
3639	PUBCHEM_CID
387525002	SNOMEDCT_US
4017615	VUID
4017615	VANDF
4834	MMSL
4836	IUPHAR_LIGAND_ID
5487	RXNORM
841	INN_ID

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Pharmaceutical products:

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Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-0220	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-0222	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-0223	TABLET, FILM COATED	25 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-0223	TABLET, FILM COATED	25 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-3112	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-3112	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-5212	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-5212	TABLET, FILM COATED	12.50 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-7225	TABLET, FILM COATED	25 mg	ORAL	NDA	22 sections
ACCURETIC	HUMAN PRESCRIPTION DRUG LABEL	2	0071-7225	TABLET, FILM COATED	25 mg	ORAL	NDA	22 sections

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