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

Stem definition	Drug id	CAS RN
diuretics, piretanide derivatives	427	28395-03-1

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: bumetanide bumethanide bufenox	A sulfamyl diuretic. Molecular weight: 364.42 Formula: C17H20N2O5S CLOGP: 3.37 LIPINSKI: 0 HAC: 7 HDO: 3 TPSA: 118.72 ALOGS: -4.15 ROTB: 8 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

bumetanide
bumethanide
bufenox

A sulfamyl diuretic.

Molecular weight: 364.42
Formula: C17H20N2O5S
CLOGP: 3.37
LIPINSKI: 0
HAC: 7
HDO: 3
TPSA: 118.72
ALOGS: -4.15
ROTB: 8

Status: OFP

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

Drug dosage:

Dose	Unit	Route
1	mg	O
1	mg	P
1	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.10 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	45 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.46 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	90 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.16 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.50 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.03 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Feb. 28, 1983	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
Fluid retention	188.61	12.73	177	23660	50869	46611356
Cardiac failure congestive	188.35	12.73	233	23604	91517	46570708
Acute kidney injury	183.19	12.73	384	23453	235471	46426754
Fluid overload	163.87	12.73	125	23712	27060	46635165
Dyspnoea	160.83	12.73	601	23236	514947	46147278
Right ventricular failure	121.94	12.73	85	23752	16008	46646217
Pulmonary arterial hypertension	105.60	12.73	95	23742	25833	46636392
Oedema peripheral	95.78	12.73	235	23602	159471	46502754
Rheumatoid arthritis	93.09	12.73	8	23829	240207	46422018
Pulmonary hypertension	93.06	12.73	103	23734	35890	46626335
Oedema	90.21	12.73	139	23698	66932	46595293
Drug ineffective	88.81	12.73	131	23706	677707	45984518
Cardiac failure	86.29	12.73	150	23687	79798	46582427
Renal failure	84.46	12.73	182	23655	113412	46548813
International normalised ratio increased	71.38	12.73	103	23734	46780	46615445
Renal impairment	65.68	12.73	128	23709	74244	46587981
Off label use	55.01	12.73	68	23769	379773	46282452
Body tinea	51.48	12.73	19	23818	916	46661309
Hyperkalaemia	50.63	12.73	92	23745	50617	46611608
Atrial fibrillation	50.31	12.73	141	23696	103449	46558776
Hypotension	45.82	12.73	237	23600	232352	46429873
Pulmonary oedema	45.15	12.73	88	23749	51017	46611208
BRASH syndrome	42.25	12.73	10	23827	96	46662129
Impaired quality of life	39.19	12.73	23	23814	3219	46659006
Exposure during pregnancy	38.29	12.73	5	23832	108207	46554018
Dyspnoea exertional	37.80	12.73	81	23756	50208	46612017
Treatment failure	36.28	12.73	3	23834	93084	46569141
Infection susceptibility increased	36.04	12.73	19	23818	2160	46660065
Chronic obstructive pulmonary disease	35.73	12.73	86	23751	57547	46604678
Gastrointestinal haemorrhage	35.30	12.73	103	23734	77270	46584955
Infusion related reaction	35.04	12.73	5	23832	101203	46561022
Inhibitory drug interaction	34.72	12.73	18	23819	1977	46660248
Left ventricular failure	34.65	12.73	25	23812	4965	46657260
Cardiac failure acute	33.67	12.73	30	23807	8048	46654177
Hypoxia	32.83	12.73	78	23759	51760	46610465
Death	31.64	12.73	285	23552	335263	46326962
Transfusion	31.01	12.73	36	23801	13195	46649030
Purpura	30.14	12.73	31	23806	9927	46652298
Bradycardia	29.99	12.73	88	23749	66210	46596015
Congestive cardiomyopathy	29.51	12.73	24	23813	5689	46656536
Joint swelling	29.34	12.73	25	23812	166048	46496177
Weight increased	28.55	12.73	162	23675	164311	46497914
Dialysis	27.96	12.73	30	23807	10086	46652139
Cellulitis	27.78	12.73	89	23748	70199	46592026
Gout	26.78	12.73	31	23806	11325	46650900
Glucose tolerance impaired	26.45	12.73	21	23816	4810	46657415
Alopecia	25.69	12.73	27	23810	162387	46499838
Drug hypersensitivity	25.49	12.73	54	23783	243771	46418454
Pleural effusion	24.97	12.73	96	23741	82856	46579369
Blood potassium decreased	24.88	12.73	58	23779	38005	46624220
Acute respiratory failure	24.31	12.73	49	23788	29089	46633136
Blood creatinine increased	24.30	12.73	90	23747	76313	46585912
Epistaxis	24.13	12.73	80	23757	64225	46598000
Respiratory failure	24.00	12.73	104	23733	94712	46567513
Pain in jaw	23.49	12.73	57	23780	38315	46623910
Haemoglobin decreased	23.02	12.73	128	23709	128821	46533404
Drug intolerance	22.64	12.73	25	23812	147024	46515201
Drug abuse	22.26	12.73	3	23834	63405	46598820
Genital infection female	21.52	12.73	6	23831	115	46662110
Cardiorenal syndrome	21.45	12.73	9	23828	611	46661614
Therapeutic product effect decreased	20.90	12.73	8	23829	82593	46579632
Oxygen saturation decreased	20.78	12.73	80	23757	69084	46593141
Intentional overdose	20.72	12.73	4	23833	64940	46597285
Rectal haemorrhage	20.47	12.73	54	23783	38201	46624024
Dehydration	20.16	12.73	145	23692	159395	46502830
Chronic left ventricular failure	19.62	12.73	7	23830	306	46661919
Therapeutic product effect incomplete	19.07	12.73	8	23829	78145	46584080
Orthopnoea	19.06	12.73	19	23818	5861	46656364
Arthralgia	18.94	12.73	109	23728	364494	46297731
Torsade de pointes	18.92	12.73	27	23810	12127	46650098
Arteriosclerosis coronary artery	18.79	12.73	22	23815	8134	46654091
Unevaluable event	18.72	12.73	59	23778	46116	46616109
Suicide attempt	18.40	12.73	3	23834	55033	46607192
Atrial flutter	18.34	12.73	23	23814	9125	46653100
Abdominal distension	18.21	12.73	80	23757	73271	46588954
Blood urea increased	18.09	12.73	40	23797	25312	46636913
Product use in unapproved indication	17.97	12.73	12	23825	90261	46571964
Paracentesis	17.82	12.73	9	23828	936	46661289
Contraindicated product administered	16.77	12.73	10	23827	79937	46582288
Injection site pain	16.73	12.73	18	23819	107134	46555091
Pneumonia	16.62	12.73	277	23560	376043	46286182
Cardiomegaly	16.53	12.73	31	23806	17451	46644774
Hospitalisation	16.40	12.73	70	23767	63315	46598910
Chronic kidney disease	16.37	12.73	52	23785	40819	46621406
Urine output decreased	16.32	12.73	24	23813	11073	46651152
Pemphigoid	15.94	12.73	17	23820	5674	46656551
Blood potassium increased	15.94	12.73	30	23807	16937	46645288
Arthropathy	15.88	12.73	12	23825	84688	46577537
Musculoskeletal stiffness	15.82	12.73	16	23821	97977	46564248
Seizure	15.76	12.73	24	23813	123030	46539195
Packed red blood cell transfusion	15.39	12.73	11	23826	2152	46660073
Confusional state	15.11	12.73	136	23701	159756	46502469
Brain natriuretic peptide increased	15.03	12.73	15	23822	4635	46657590
Hepatic enzyme increased	14.81	12.73	12	23825	81775	46580450
Anaemia	14.68	12.73	197	23640	255582	46406643
Injection site erythema	14.67	12.73	10	23827	74417	46587808
Lung transplant	14.62	12.73	12	23825	2880	46659345
Drug monitoring procedure not performed	14.47	12.73	6	23831	395	46661830
Urosepsis	14.24	12.73	27	23810	15326	46646899
Claudication of jaw muscles	14.23	12.73	4	23833	79	46662146
Subacute cutaneous lupus erythematosus	14.23	12.73	10	23827	1905	46660320
Generalised oedema	14.20	12.73	26	23811	14373	46647852
Blood sodium decreased	14.08	12.73	33	23804	21693	46640532
Oxygen consumption increased	14.08	12.73	13	23824	3650	46658575
Right ventricular dysfunction	13.85	12.73	9	23828	1509	46660716
Compartment syndrome	13.84	12.73	10	23827	1989	46660236
Malignant neoplasm progression	13.79	12.73	8	23829	64918	46597307
Asthenia	13.72	12.73	229	23608	310846	46351379
Hypoaesthesia	13.55	12.73	25	23812	118844	46543381
Diaphragmatic disorder	13.22	12.73	6	23831	492	46661733
Incarcerated umbilical hernia	13.05	12.73	3	23834	25	46662200
Diuretic therapy	13.01	12.73	4	23833	109	46662116
Brain stem stroke	12.99	12.73	5	23832	271	46661954
Blood aldosterone abnormal	12.85	12.73	3	23834	27	46662198
Bone density decreased	12.79	12.73	20	23817	9732	46652493

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
Acute kidney injury	211.10	13.46	497	17986	273345	29660650
Cardiac failure congestive	166.04	13.46	231	18252	84176	29849819
Cardiac failure	127.64	13.46	203	18280	83215	29850780
Fluid retention	106.30	13.46	102	18381	24896	29909099
Dyspnoea	104.13	13.46	443	18040	332852	29601143
Pulmonary hypertension	79.64	13.46	77	18406	18959	29915036
Fluid overload	64.83	13.46	69	18414	19023	29914972
Pulmonary arterial hypertension	45.39	13.46	41	18442	9260	29924735
Oedema peripheral	44.50	13.46	155	18328	105677	29828318
Drug ineffective	44.16	13.46	90	18393	340297	29593698
Renal failure	41.16	13.46	173	18310	128793	29805202
Right ventricular failure	40.35	13.46	36	18447	8000	29925995
Blood ketone body increased	39.64	13.46	13	18470	361	29933634
Oedema	39.43	13.46	84	18399	42909	29891086
Toxicity to various agents	34.62	13.46	35	18448	177148	29756847
Hypotension	32.93	13.46	224	18259	200341	29733654
International normalised ratio increased	32.51	13.46	83	18400	47656	29886339
Completed suicide	31.55	13.46	11	18472	99481	29834514
Renal impairment	30.88	13.46	118	18365	84066	29849929
Hyperkalaemia	30.64	13.46	100	18383	65910	29868085
Peripheral swelling	29.69	13.46	94	18389	60980	29873015
Gastrointestinal haemorrhage	29.00	13.46	115	18368	83331	29850664
Atrial fibrillation	25.59	13.46	133	18350	107991	29826004
Ventricular tachycardia	24.67	13.46	49	18434	23813	29910182
Dyspnoea exertional	24.53	13.46	62	18421	35368	29898627
Pulmonary oedema	24.48	13.46	71	18412	43904	29890091
Off label use	23.70	13.46	77	18406	249213	29684782
Cardiac failure chronic	23.17	13.46	23	18460	5840	29928155
Pulmonary renal syndrome	22.35	13.46	7	18476	167	29933828
Febrile neutropenia	22.07	13.46	20	18463	106673	29827322
Blood creatinine increased	22.03	13.46	113	18370	91262	29842733
Pyrexia	21.58	13.46	101	18382	294388	29639607
Orthostatic hypotension	21.00	13.46	46	18437	23933	29910062
Cardiac failure acute	20.77	13.46	27	18456	9182	29924813
Hepatic cirrhosis	20.47	13.46	36	18447	15963	29918032
Neutropenia	20.22	13.46	30	18453	128510	29805485
Anti-neutrophil cytoplasmic antibody positive vasculitis	19.77	13.46	9	18474	614	29933381
Chronic kidney disease	19.08	13.46	59	18424	37779	29896216
Venous pressure jugular increased	18.63	13.46	9	18474	702	29933293
Weight increased	18.30	13.46	93	18390	74820	29859175
Weight bearing difficulty	16.86	13.46	9	18474	866	29933129
Packed red blood cell transfusion	16.76	13.46	11	18472	1549	29932446
Reaction to excipient	16.73	13.46	7	18476	389	29933606
Orthopnoea	16.46	13.46	17	18466	4523	29929472
Hypovolaemia	16.03	13.46	23	18460	8582	29925413
Rheumatoid arthritis	16.02	13.46	3	18480	41194	29892801
Polyuria	15.83	13.46	21	18462	7285	29926710
Amyloidosis	15.81	13.46	12	18471	2127	29931868
Ascites	15.39	13.46	53	18430	35868	29898127
Bradycardia	15.06	13.46	80	18403	65446	29868549
Dyspnoea paroxysmal nocturnal	14.47	13.46	9	18474	1156	29932839
Hepatic function abnormal	14.43	13.46	4	18479	41941	29892054
Hungry bone syndrome	14.33	13.46	4	18479	63	29933932
Transitional cell carcinoma	14.32	13.46	11	18472	1984	29932011
Blood potassium increased	14.08	13.46	31	18452	16182	29917813
Abdominal cavity drainage	14.07	13.46	6	18477	350	29933645
Incarcerated hernia	14.04	13.46	5	18478	179	29933816
Intra-abdominal haemorrhage	13.82	13.46	11	18472	2091	29931904
Faeces discoloured	13.65	13.46	28	18455	13918	29920077
Suicide attempt	13.59	13.46	3	18480	36694	29897301
Vasculitic rash	13.55	13.46	8	18475	935	29933060

Pharmacologic Action:

Source	Code	Description
ATC	C03CA02	CARDIOVASCULAR SYSTEM DIURETICS HIGH-CEILING DIURETICS Sulfonamides, plain
ATC	C03CB02	CARDIOVASCULAR SYSTEM DIURETICS HIGH-CEILING DIURETICS Sulfonamides and potassium in combination
ATC	C03EB02	CARDIOVASCULAR SYSTEM DIURETICS DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION High-ceiling diuretics and potassium-sparing agents
FDA PE	N0000175366	Increased Diuresis at Loop of Henle
FDA EPC	N0000175590	Loop Diuretic
CHEBI has role	CHEBI:35498	diuretics
CHEBI has role	CHEBI:131770	cystic fibrosis transmembrane conductance regulator inhibitors
MeSH PA	D004232	Diuretics
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D045283	Natriuretic Agents
MeSH PA	D049994	Sodium Potassium Chloride Symporter Inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Edema	indication	267038008
Edema due to Hepatic Cirrhosis	indication
Peripheral Edema due to Chronic Heart Failure	indication
Renal Disease with Edema	indication
Pulmonary Edema due to Chronic Heart Failure	indication
Hypertensive disorder	off-label use	38341003	DOID:10763
Hypercalcemia	off-label use	66931009	DOID:12678
Decompensated cardiac failure	off-label use	195111005
Anuria	contraindication	2472002	DOID:2983
Hypocalcemia	contraindication	5291005
Hypovolemia	contraindication	28560003
Hyperuricemia	contraindication	35885006	DOID:1920
Hypokalemia	contraindication	43339004
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Oliguria	contraindication	83128009
Hearing disorder	contraindication	128540005
Hypomagnesemia	contraindication	190855004
Disease of liver	contraindication	235856003	DOID:409
Thrombocytopenic disorder	contraindication	302215000	DOID:1588

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.36	acidic
pKa2	9.88	acidic
pKa3	0.86	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 1	Transporter	Q13621	S12A1_HUMAN	INHIBITOR	Ki	7.60	WOMBAT-PK	CHEMBL
Sodium/potassium-transporting ATPase subunit alpha-1	Transporter	P05023	AT1A1_HUMAN		Kd	7.52	WOMBAT-PK
Solute carrier family 12 member 2	Transporter	P55011	S12A2_HUMAN	INHIBITOR	IC50	5.60	IUPHAR
G-protein coupled receptor 35	GPCR	Q9HC97	GPR35_HUMAN	AGONIST	EC50	5.54	IUPHAR

External reference:

ID	Source
4017794	VUID
N0000146155	NUI
D00247	KEGG_DRUG
4017794	VANDF
C0006376	UMLSCUI
CHEBI:3213	CHEBI
CHEMBL1072	ChEMBL_ID
DB00887	DRUGBANK_ID
D002034	MESH_DESCRIPTOR_UI
2943	INN_ID
2471	PUBCHEM_CID
4837	IUPHAR_LIGAND_ID
0Y2S3XUQ5H	UNII
1808	RXNORM
3606	MMSL
4304	MMSL
d00179	MMSL
002312	NDDF
387498005	SNOMEDCT_US
86647004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0128	TABLET	0.50 mg	ORAL	ANDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0129	TABLET	1 mg	ORAL	ANDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0130	TABLET	2 mg	ORAL	ANDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0409-1412	INJECTION, SOLUTION	0.25 mg	INTRAMUSCULAR	ANDA	20 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8361	TABLET	1 mg	ORAL	ANDA	20 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8362	TABLET	2 mg	ORAL	ANDA	20 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8393	TABLET	1 mg	ORAL	ANDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8394	TABLET	2 mg	ORAL	ANDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0641-6007	INJECTION	0.25 mg	INTRAMUSCULAR	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0641-6008	INJECTION	0.25 mg	INTRAMUSCULAR	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0641-6161	INJECTION	0.25 mg	INTRAMUSCULAR	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0641-6162	INJECTION	0.25 mg	INTRAMUSCULAR	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0832-0540	TABLET	0.50 mg	ORAL	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0832-0541	TABLET	1 mg	ORAL	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0832-0542	TABLET	2 mg	ORAL	ANDA	22 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7016	TABLET	1 mg	ORAL	ANDA	21 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	14539-700	TABLET	0.50 mg	ORAL	ANDA	19 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	14539-701	TABLET	1 mg	ORAL	ANDA	19 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	14539-702	TABLET	2 mg	ORAL	ANDA	19 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	16714-831	TABLET	0.50 mg	ORAL	ANDA	18 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	16714-832	TABLET	1 mg	ORAL	ANDA	18 sections
bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	16714-833	TABLET	2 mg	ORAL	ANDA	18 sections
Bumex	HUMAN PRESCRIPTION DRUG LABEL	1	30698-630	TABLET	0.50 mg	ORAL	NDA	21 sections
Bumex	HUMAN PRESCRIPTION DRUG LABEL	1	30698-631	TABLET	1 mg	ORAL	NDA	21 sections
Bumex	HUMAN PRESCRIPTION DRUG LABEL	1	30698-632	TABLET	2 mg	ORAL	NDA	21 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	33261-983	TABLET	1 mg	ORAL	ANDA	20 sections
Bumetanide	Human Prescription Drug Label	1	42799-119	TABLET	0.50 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Bumetanide	Human Prescription Drug Label	1	42799-120	TABLET	1 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Bumetanide	Human Prescription Drug Label	1	42799-121	TABLET	2 mg	ORAL	NDA AUTHORIZED GENERIC	23 sections
Bumetanide	HUMAN PRESCRIPTION DRUG LABEL	1	43353-288	TABLET	1 mg	ORAL	ANDA	21 sections