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

Stem definition	Drug id	CAS RN
diuretics, chlorothiazide derivatives	305	73-48-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: bendroflumethiazide bendrofluazide benzhydroflumethiazide benzidroflumetiazide benzydroflumethiazide benzylhydroflumethiazide benzylrodiuran	A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810) Molecular weight: 421.41 Formula: C15H14F3N3O4S2 CLOGP: 1.73 LIPINSKI: 0 HAC: 7 HDO: 3 TPSA: 118.36 ALOGS: -3.29 ROTB: 4 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

bendroflumethiazide
bendrofluazide
benzhydroflumethiazide
benzidroflumetiazide
benzydroflumethiazide
benzylhydroflumethiazide
benzylrodiuran

A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)

Molecular weight: 421.41
Formula: C15H14F3N3O4S2
CLOGP: 1.73
LIPINSKI: 0
HAC: 7
HDO: 3
TPSA: 118.36
ALOGS: -3.29
ROTB: 4

Status: OFM

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

Drug dosage:

Dose	Unit	Route
2.50	mg	O
2.50	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.11 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	21 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.79 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	90 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
Dec. 7, 1959	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
Cardiospasm	215.14	26.45	54	12367	1853	63474748
Palmoplantar keratoderma	212.40	26.45	54	12367	1953	63474648
Lip swelling	212.17	26.45	109	12312	30954	63445647
Pruritus genital	202.09	26.45	55	12366	2599	63474002
Hyponatraemia	201.22	26.45	170	12251	111730	63364871
Sleep terror	196.91	26.45	54	12367	2626	63473975
Tension headache	194.15	26.45	62	12359	5124	63471477
Atrial tachycardia	180.84	26.45	56	12365	4184	63472417
Carotid artery occlusion	167.04	26.45	54	12367	4640	63471961
Drug ineffective	151.68	26.45	15	12406	1044750	62431851
Anosmia	146.97	26.45	54	12367	6806	63469795
Hallucination	141.08	26.45	103	12318	54714	63421887
Immunisation	135.65	26.45	34	12387	1159	63475442
Facial pain	127.67	26.45	55	12366	10506	63466095
Subarachnoid haemorrhage	126.93	26.45	60	12361	14223	63462378
Pain of skin	122.56	26.45	55	12366	11579	63465022
Intentional product misuse	116.49	26.45	96	12325	60821	63415780
Diplopia	113.99	26.45	66	12355	23662	63452939
Eye pruritus	111.71	26.45	60	12361	18611	63457990
Blindness	111.32	26.45	63	12358	21636	63454965
Vasculitis	107.50	26.45	58	12363	18151	63458450
Ventricular tachycardia	102.47	26.45	58	12363	19921	63456680
Amnesia	98.82	26.45	84	12337	55501	63421100
Angioedema	94.64	26.45	77	12344	47888	63428713
Muscle twitching	92.59	26.45	54	12367	19614	63456987
Pulmonary pain	88.00	26.45	31	12390	3459	63473142
Disturbance in social behaviour	83.93	26.45	31	12390	3962	63472639
Palpitations	82.72	26.45	106	12315	112664	63363937
Tinnitus	76.25	26.45	60	12361	35568	63441033
Disturbance in attention	72.58	26.45	60	12361	38129	63438472
Paranoia	68.36	26.45	37	12384	11642	63464959
Transient ischaemic attack	66.96	26.45	57	12364	37696	63438905
Cognitive disorder	65.59	26.45	67	12354	55748	63420853
Mouth swelling	64.98	26.45	27	12394	4713	63471888
Visual impairment	64.46	26.45	81	12340	84365	63392236
Amyloid arthropathy	63.30	26.45	16	12405	564	63476037
Confusional state	61.68	26.45	140	12281	236240	63240361
Malaise	59.09	26.45	197	12224	415757	63060844
Rash papular	58.20	26.45	37	12384	15665	63460936
Dry skin	52.31	26.45	60	12361	56827	63419774
Vomiting	49.31	26.45	228	12193	559389	62917212
Hyperhidrosis	46.54	26.45	79	12342	107757	63368844
Acute kidney injury	45.86	26.45	134	12287	263281	63213320
Agitation	45.08	26.45	57	12364	59700	63416901
Abnormal behaviour	43.51	26.45	35	12386	21391	63455210
Superinfection	43.13	26.45	17	12404	2590	63474011
Disorientation	42.11	26.45	45	12376	39407	63437194
Hypokalaemia	42.11	26.45	74	12347	103730	63372871
Tachycardia	41.33	26.45	79	12342	118077	63358524
Nail dystrophy	41.22	26.45	13	12408	1030	63475571
Ejection fraction decreased	40.17	26.45	34	12387	22298	63454303
Lethargy	40.00	26.45	52	12369	55955	63420646
Death	39.69	26.45	12	12409	374369	63102232
Weight increased	39.61	26.45	3	12418	260789	63215812
Monoclonal B-cell lymphocytosis	39.02	26.45	7	12414	43	63476558
Nasopharyngitis	38.41	26.45	3	12418	254254	63222347
Duodenal ulcer repair	37.63	26.45	7	12414	54	63476547
Muscular weakness	37.02	26.45	77	12344	122276	63354325
Infusion related reaction	36.80	26.45	3	12418	245518	63231083
Myocardial infarction	36.43	26.45	68	12353	99825	63376776
Orthostatic hypotension	36.41	26.45	40	12381	36120	63440481
Hypersensitivity vasculitis	35.68	26.45	17	12404	4095	63472506
Duodenogastric reflux	34.11	26.45	7	12414	94	63476507
Femoral neck fracture	33.88	26.45	21	12400	8502	63468099
Drug abuse	32.43	26.45	54	12367	72464	63404137
Swelling face	32.12	26.45	50	12371	63425	63413176
Blood glucose increased	31.77	26.45	58	12363	83698	63392903
Cellulitis	31.40	26.45	57	12364	81901	63394700
Emotional distress	31.04	26.45	35	12386	32514	63444087
Lower respiratory tract infection	30.77	26.45	75	12346	132232	63344369
Swelling	30.70	26.45	8	12413	275370	63201231
Sinusitis	28.49	26.45	5	12416	226648	63249953
Dehydration	28.05	26.45	86	12335	173268	63303333
Hypomagnesaemia	27.57	26.45	31	12390	28706	63447895
Neutropenic sepsis	27.47	26.45	24	12397	16414	63460187
Dizziness	27.23	26.45	160	12261	429765	63046836

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
Cardiospasm	271.00	33.89	66	8825	1522	34946518
Lip swelling	253.54	33.89	109	8782	15971	34932069
Palmoplantar keratoderma	252.55	33.89	65	8826	1888	34946152
Pruritus genital	240.00	33.89	64	8827	2140	34945900
Sleep terror	236.80	33.89	64	8827	2254	34945786
Tension headache	232.93	33.89	67	8824	2975	34945065
Atrial tachycardia	220.96	33.89	67	8824	3578	34944462
Facial pain	211.39	33.89	65	8826	3639	34944401
Carotid artery occlusion	210.82	33.89	65	8826	3672	34944368
Anosmia	210.25	33.89	66	8825	3958	34944082
Pain of skin	186.98	33.89	67	8824	6042	34941998
Immunisation	184.96	33.89	45	8846	1032	34947008
Eye pruritus	173.69	33.89	67	8824	7422	34940618
Subarachnoid haemorrhage	171.10	33.89	77	8814	12558	34935482
Muscle twitching	169.48	33.89	72	8819	10226	34937814
Vasculitis	147.11	33.89	67	8824	11229	34936811
Rash papular	143.50	33.89	64	8827	10214	34937826
Pericarditis	142.04	33.89	66	8825	11579	34936461
Blindness	140.72	33.89	71	8820	14915	34933125
Migraine	122.15	33.89	68	8823	17410	34930630
Diplopia	119.00	33.89	66	8825	16777	34931263
Abdominal discomfort	113.48	33.89	105	8786	59730	34888310
Amnesia	110.14	33.89	74	8817	26489	34921551
Hallucination	108.71	33.89	96	8795	51402	34896638
Tinnitus	105.54	33.89	65	8826	20053	34927987
Disturbance in attention	104.51	33.89	71	8820	25874	34922166
Transient ischaemic attack	100.51	33.89	71	8820	27542	34920498
Angioedema	98.07	33.89	79	8812	37295	34910745
Cognitive disorder	98.06	33.89	71	8820	28622	34919418
Palpitations	97.53	33.89	81	8810	39905	34908135
Ventricular tachycardia	93.64	33.89	67	8824	26512	34921528
Intentional product misuse	92.21	33.89	83	8808	45528	34902512
Alopecia	91.84	33.89	64	8827	24291	34923749
Visual impairment	86.21	33.89	72	8819	35730	34912310
Dry skin	81.77	33.89	66	8825	31221	34916819
Peripheral swelling	78.59	33.89	97	8794	76444	34871596
Radiation inflammation	69.55	33.89	20	8871	885	34947155
Memory impairment	68.80	33.89	69	8822	43249	34904791
Abdominal pain upper	64.52	33.89	85	8806	71405	34876635
COVID-19	63.59	33.89	88	8803	77462	34870578
Pulmonary pain	63.59	33.89	20	8871	1204	34946836
Drug ineffective	61.51	33.89	20	8871	456731	34491309
Feeling abnormal	61.46	33.89	78	8813	63157	34884883
Heart rate increased	56.22	33.89	64	8827	46279	34901761
Neutropenic sepsis	56.18	33.89	38	8853	13729	34934311
Malaise	53.33	33.89	134	8757	185691	34762349
Hyponatraemia	50.82	33.89	82	8809	82609	34865431
Blood glucose increased	50.66	33.89	73	8818	66645	34881395
Death	49.18	33.89	20	8871	398029	34550011
Muscular weakness	48.54	33.89	75	8816	72822	34875218
Lower respiratory tract infection	45.86	33.89	48	8843	31589	34916451
Tachycardia	44.04	33.89	78	8813	84694	34863346
Hyperhidrosis	43.71	33.89	73	8818	75619	34872421
Toxicity to various agents	36.91	33.89	4	8887	200358	34747682
Asthenia	36.12	33.89	9	8882	245242	34702798
Chest pain	34.82	33.89	90	8801	126672	34821368

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
Cardiospasm	447.43	25.27	115	20981	3186	79720106
Lip swelling	433.46	25.27	213	20883	40698	79682594
Palmoplantar keratoderma	429.16	25.27	114	20982	3602	79719690
Pruritus genital	407.90	25.27	114	20982	4372	79718920
Sleep terror	404.03	25.27	113	20983	4345	79718947
Tension headache	395.89	25.27	124	20972	7087	79716205
Atrial tachycardia	372.22	25.27	118	20978	7015	79716277
Carotid artery occlusion	347.93	25.27	114	20982	7533	79715759
Anosmia	335.56	25.27	115	20981	8729	79714563
Facial pain	301.65	25.27	116	20980	12234	79711058
Pain of skin	292.99	25.27	119	20977	14494	79708798
Immunisation	291.25	25.27	75	21021	2092	79721200
Subarachnoid haemorrhage	272.87	25.27	132	20964	24333	79698959
Hyponatraemia	267.75	25.27	280	20816	177568	79545724
Eye pruritus	263.18	25.27	122	20974	20448	79702844
Blindness	245.71	25.27	129	20967	28254	79695038
Muscle twitching	238.72	25.27	121	20975	24643	79698649
Hallucination	237.17	25.27	190	20906	85555	79637737
Vasculitis	234.26	25.27	120	20976	24982	79698310
Diplopia	220.44	25.27	127	20969	33339	79689953
Amnesia	203.19	25.27	153	20943	62904	79660388
Intentional product misuse	188.08	25.27	174	20922	94991	79628301
Rash papular	185.09	25.27	98	20998	21818	79701474
Drug ineffective	178.94	25.27	35	21061	1080878	78642414
Ventricular tachycardia	177.11	25.27	120	20976	41815	79681477
Angioedema	171.89	25.27	150	20946	75885	79647407
Tinnitus	171.07	25.27	120	20976	44213	79679079
Disturbance in attention	167.50	25.27	125	20971	50676	79672616
Transient ischaemic attack	159.04	25.27	123	20973	52572	79670720
Cognitive disorder	148.17	25.27	133	20963	69793	79653499
Palpitations	146.66	25.27	174	20922	126436	79596856
Pulmonary pain	142.18	25.27	51	21045	4422	79718870
Visual impairment	138.29	25.27	145	20951	91986	79631306
Dry skin	127.88	25.27	121	20975	67874	79655418
Malaise	102.47	25.27	323	20773	489546	79233746
Migraine	100.85	25.27	120	20976	87373	79635919
Blood glucose increased	83.72	25.27	126	20970	114849	79608443
Memory impairment	83.58	25.27	124	20972	111610	79611682
Abdominal discomfort	79.85	25.27	193	20903	250534	79472758
Neutropenic sepsis	79.07	25.27	62	21034	27002	79696290
Muscular weakness	78.13	25.27	147	20949	160582	79562710
Pericarditis	76.98	25.27	115	20981	104121	79619171
Hyperhidrosis	75.43	25.27	140	20956	151352	79571940
Peripheral swelling	74.84	25.27	197	20899	269420	79453872
Death	73.59	25.27	29	21067	566485	79156807
Tachycardia	72.43	25.27	151	20945	177617	79545675
Feeling abnormal	70.52	25.27	140	20956	159059	79564233
Confusional state	70.33	25.27	214	20882	317783	79405509
Radiation inflammation	68.76	25.27	20	21076	885	79722407
Disturbance in social behaviour	68.31	25.27	31	21065	4939	79718353
COVID-19	67.85	25.27	137	20959	157537	79565755
Heart rate increased	65.73	25.27	116	20980	120608	79602684
Abdominal pain upper	65.65	25.27	167	20929	223652	79499640
Lethargy	63.34	25.27	92	21004	81200	79642092
Lower respiratory tract infection	62.54	25.27	118	20978	129102	79594190
Weight increased	60.91	25.27	3	21093	277383	79445909
Amyloid arthropathy	58.51	25.27	16	21080	564	79722728
Dehydration	55.75	25.27	168	20928	248019	79475273
Toxicity to various agents	54.00	25.27	22	21074	421518	79301774
Mouth swelling	53.75	25.27	28	21068	6023	79717269
Vomiting	52.62	25.27	328	20768	665500	79057792
Myocardial infarction	50.48	25.27	134	20962	183995	79539297
Orthostatic hypotension	50.35	25.27	68	21028	56096	79667196
Pruritus	47.96	25.27	219	20877	394429	79328863
Completed suicide	47.28	25.27	5	21091	245762	79477530
Acute kidney injury	46.18	25.27	264	20832	519140	79204152
Paranoia	45.20	25.27	39	21057	19393	79703899
Weight decreased	44.73	25.27	19	21077	355179	79368113
Rheumatoid arthritis	43.48	25.27	3	21093	208467	79514825
Dizziness	41.93	25.27	260	20836	526181	79197111
Thrombocytopenia	40.78	25.27	10	21086	265249	79458043
Agitation	39.75	25.27	84	21012	99631	79623661
Swelling face	39.47	25.27	69	21027	71143	79652149
Alopecia	38.87	25.27	142	20954	231213	79492079
Chest pain	38.31	25.27	162	20934	282142	79441150
Nail dystrophy	37.74	25.27	13	21083	1000	79722292
Sinusitis	37.54	25.27	4	21092	195497	79527795
Anaemia	35.79	25.27	39	21057	444976	79278316
Anxiety	34.01	25.27	143	20953	248369	79474923
Swelling	33.63	25.27	8	21088	216703	79506589
Duodenal ulcer repair	33.63	25.27	7	21089	73	79723219
Lid lag	33.46	25.27	7	21089	75	79723217
Infusion related reaction	32.90	25.27	10	21086	230227	79493065
General physical health deterioration	32.65	25.27	16	21080	275222	79448070
Adverse drug reaction	32.56	25.27	61	21035	66331	79656961
Product use issue	32.06	25.27	8	21088	209814	79513478
Hepatic enzyme increased	32.01	25.27	5	21091	182605	79540687
Back pain	31.28	25.27	161	20935	304019	79419273
Duodenogastric reflux	31.16	25.27	7	21089	107	79723185
Hypomagnesaemia	30.73	25.27	49	21047	46862	79676430
Mixed dementia	29.23	25.27	8	21088	283	79723009
Hypokalaemia	29.06	25.27	94	21002	143946	79579346
Superinfection	28.05	25.27	17	21079	4885	79718407
White blood cell count decreased	27.22	25.27	8	21088	188280	79535012
Treatment failure	27.04	25.27	6	21090	170480	79552812
Platelet count decreased	26.84	25.27	9	21087	194655	79528637
Neutropenia	25.66	25.27	23	21073	287687	79435605
Liver function test abnormal	25.32	25.27	54	21042	64421	79658871

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C03AA01	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, plain
ATC	C03AB01	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides and potassium in combination
ATC	C03EA13	CARDIOVASCULAR SYSTEM DIURETICS DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION Low-ceiling diuretics and potassium-sparing agents
FDA CS	M0471776	Thiazides
FDA PE	N0000175359	Increased Diuresis
FDA EPC	N0000175419	Thiazide Diuretic
CHEBI has role	CHEBI:35498	diuretics
CHEBI has role	CHEBI:35674	antihypertensive drugs
MeSH PA	D000959	Antihypertensive Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D004232	Diuretics
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D045283	Natriuretic Agents
MeSH PA	D049993	Sodium Chloride Symporter Inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Hypertensive disorder	indication	38341003	DOID:10763
Anuria	contraindication	2472002	DOID:2983
Bronchospasm	contraindication	4386001
Hypercholesterolemia	contraindication	13644009
Complete atrioventricular block	contraindication	27885002
Depressive disorder	contraindication	35489007
Hyperuricemia	contraindication	35885006	DOID:1920
Anaphylaxis	contraindication	39579001
Hypokalemia	contraindication	43339004
Sinus bradycardia	contraindication	49710005
Systemic lupus erythematosus	contraindication	55464009	DOID:9074
Sympathectomy	contraindication	57071006
Acute nephropathy	contraindication	58574008
Hypercalcemia	contraindication	66931009	DOID:12678
Hyperparathyroidism	contraindication	66999008	DOID:13543
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Oliguria	contraindication	83128009
Pulmonary emphysema	contraindication	87433001
Cardiogenic shock	contraindication	89138009
Hyponatremia	contraindication	89627008
Gout	contraindication	90560007	DOID:13189
Kidney disease	contraindication	90708001	DOID:557
Myasthenia gravis	contraindication	91637004	DOID:437
Hypomagnesemia	contraindication	190855004
Partial atrioventricular block	contraindication	195039008
Decompensated cardiac failure	contraindication	195111005
Acute pancreatitis	contraindication	197456007	DOID:2913
Disease of liver	contraindication	235856003	DOID:409
Raynaud's phenomenon	contraindication	266261006
Neonatal hyperbilirubinemia	contraindication	281610001
Pregnancy, function	contraindication	289908002
Severe chronic obstructive pulmonary disease	contraindication	313299006
Right ventricular failure	contraindication	367363000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.79	acidic
pKa2	10.52	acidic
pKa3	1.03	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
Solute carrier family 12 member 3	Transporter	P55017	S12A3_HUMAN	INHIBITOR	A2	8.30	WOMBAT-PK	CHEMBL
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN				WOMBAT-PK
Carbonic anhydrase 1	Enzyme	P00915	CAH1_HUMAN				WOMBAT-PK
Carbonic anhydrase 4	Enzyme	P22748	CAH4_HUMAN				WOMBAT-PK
Calcium-activated potassium channel subunit alpha-1	Ion channel	Q12791	KCMA1_HUMAN				WOMBAT-PK

External reference:

ID	Source
4017612	VUID
N0000145992	NUI
D00650	KEGG_DRUG
1369	RXNORM
C0004975	UMLSCUI
CHEBI:59243	CHEBI
CHEMBL1684	ChEMBL_ID
D001539	MESH_DESCRIPTOR_UI
DB00436	DRUGBANK_ID
2315	PUBCHEM_CID
7122	IUPHAR_LIGAND_ID
994	INN_ID
5Q52X6ICJI	UNII
3020	MMSL
4252	MMSL
d00641	MMSL
387520007	SNOMEDCT_US
91135008	SNOMEDCT_US
4017612	VANDF
002297	NDDF

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Nadolol and Bendroflumethiazide	HUMAN PRESCRIPTION DRUG LABEL	2	0115-5311	TABLET	5 mg	ORAL	ANDA	25 sections
Nadolol and Bendroflumethiazide	HUMAN PRESCRIPTION DRUG LABEL	2	0115-5322	TABLET	5 mg	ORAL	ANDA	25 sections