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Stem definition	Drug id	CAS RN
	1783	17560-51-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: SR72022 zaroxolyn metolazone metozalone	Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies. Molecular weight: 365.83 Formula: C16H16ClN3O3S CLOGP: 2.06 LIPINSKI: 0 HAC: 6 HDO: 2 TPSA: 92.50 ALOGS: -3.95 ROTB: 2 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

SR72022
zaroxolyn
metolazone
metozalone

Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.

Molecular weight: 365.83
Formula: C16H16ClN3O3S
CLOGP: 2.06
LIPINSKI: 0
HAC: 6
HDO: 2
TPSA: 92.50
ALOGS: -3.95
ROTB: 2

Status: OFP

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

Drug dosage:

Dose	Unit	Route
5	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.78 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System)	4	Bocci G, Oprea TI, Benet LZ
BA (Bioavailability)	65 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1.60 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	1.40 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.05 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	20 hours	Lombardo F, Berellini G, Obach RS
S (Water solubility)	0.02 mg/mL	Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	1.676		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	16.711		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	14.158	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	1.510	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	22.590	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	34.630	%	High	1
herg	hERG pIC50	4.449	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	1.102	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	4.710	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	23.190	%	High	1
kinase-safety-class	ACVR2A,ACVR2B,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,ITK,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK1,MAPK10,MAPK14,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ZAP70	50
kinase-selectivity-class	AXL,GRK2,MAP2K6,MAPKAPK3,PDK4,SIK2,TEK	7
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	8.318		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	12.677		High	1
mppb	Mouse plasma protein binding (% unbound)	20.300		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	32.359		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	32.420	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	6.194	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	81.470	%	High	1
rppb	Rat plasma protein binding (% unbound)	22.110	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	30.903	uM	High	1

Approvals:

Date	Agency	Company	Orphan
Nov. 27, 1973	FDA	UCB INC

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
Cardiac failure congestive	314.27	15.91	207	16619	98487	90513134
Hypervolaemia	308.86	15.91	141	16685	32616	90579005
Pulmonary arterial hypertension	266.78	15.91	119	16707	26068	90585553
Fluid retention	256.90	15.91	175	16651	87916	90523705
Right ventricular failure	214.10	15.91	93	16733	19112	90592509
Dyspnoea	175.61	15.91	454	16372	880501	89731120
Acute kidney injury	152.44	15.91	238	16588	320149	90291472
Pulmonary hypertension	144.49	15.91	93	16733	42430	90569191
Death	127.44	15.91	269	16557	456282	90155339
Oedema peripheral	108.09	15.91	181	16645	257734	90353887
Drug ineffective	105.15	15.91	64	16762	1384234	89227387
Acute respiratory failure	90.20	15.91	70	16756	42848	90568773
Renal failure	85.12	15.91	113	16713	130894	90480727
Gastrointestinal haemorrhage	83.32	15.91	93	16733	90155	90521466
Electrolyte imbalance	83.28	15.91	53	16773	23692	90587929
Hypokalaemia	81.99	15.91	111	16715	131005	90480616
Atrial fibrillation	81.86	15.91	112	16714	133499	90478122
Cardiac failure acute	78.01	15.91	40	16786	11889	90599732
Calcium deficiency	76.99	15.91	22	16804	1311	90610310
Hypotension	75.17	15.91	178	16648	325219	90286402
Dyspnoea exertional	74.59	15.91	79	16747	72209	90539412
Cardiac failure	70.43	15.91	94	16732	109402	90502219
Off label use	66.84	15.91	64	16762	1102188	89509433
Chronic kidney disease	66.81	15.91	63	16763	50128	90561493
Pulmonary oedema	66.10	15.91	69	16757	62011	90549610
Hypoxia	65.77	15.91	74	16752	72325	90539296
Infusion related reaction	64.79	15.91	3	16823	416777	90194844
Torsade de pointes	61.12	15.91	37	16789	15145	90596476
Respiratory failure	58.97	15.91	90	16736	118328	90493293
Blood potassium decreased	58.03	15.91	57	16769	47670	90563951
Ascites	56.16	15.91	56	16770	47684	90563937
Oedema	55.64	15.91	118	16708	200177	90411444
Gout	55.09	15.91	36	16790	16823	90594798
Maternal exposure during pregnancy	54.66	15.91	3	16823	360060	90251561
Hospitalisation	53.69	15.91	90	16736	128010	90483611
Dermatitis exfoliative	52.66	15.91	24	16802	5512	90606109
Systemic lupus erythematosus	52.02	15.91	4	16822	361892	90249729
Joint swelling	49.39	15.91	16	16810	503284	90108337
Synovitis	49.28	15.91	3	16823	329749	90281872
Transfusion	49.13	15.91	34	16792	17454	90594167
Hyperkalaemia	48.39	15.91	60	16766	64904	90546717
Glossodynia	47.86	15.91	3	16823	321776	90289845
Cholecystitis	47.57	15.91	33	16793	17007	90594614
Alopecia	46.39	15.91	17	16809	495054	90116567
Cardiac arrest	45.67	15.91	75	16751	104860	90506761
Metabolic alkalosis	45.54	15.91	19	16807	3530	90608091
Dehydration	45.51	15.91	107	16719	194340	90417281
Pain in jaw	45.21	15.91	50	16776	47935	90563686
Rheumatoid arthritis	44.59	15.91	7	16819	362607	90249014
Cor pulmonale	44.13	15.91	16	16810	2044	90609577
Blood creatinine increased	42.16	15.91	71	16755	101315	90510306
Urine chloride decreased	40.96	15.91	8	16818	87	90611534
Arthropathy	40.90	15.91	9	16817	366233	90245388
Therapeutic product effect decreased	40.07	15.91	3	16823	277568	90334053
Hepatic enzyme increased	40.01	15.91	9	16817	360727	90250894
Contraindicated product administered	39.76	15.91	6	16820	320133	90291488
Discomfort	39.51	15.91	3	16823	274332	90337289
Pericardial effusion	39.31	15.91	41	16785	36792	90574829
Rash	37.71	15.91	56	16770	796044	89815577
Drug intolerance	37.69	15.91	18	16808	447573	90164048
Blood urea increased	36.36	15.91	36	16790	30377	90581244
Urine sodium decreased	36.32	15.91	8	16818	162	90611459
Musculoskeletal stiffness	35.83	15.91	6	16820	296526	90315095
Renal impairment	35.09	15.91	67	16759	105354	90506267
Oxygen consumption increased	34.75	15.91	17	16809	4572	90607049
Arthralgia	32.89	15.91	59	16767	778463	89833158
Cellulitis	32.83	15.91	60	16766	91277	90520344
Multiple organ dysfunction syndrome	31.30	15.91	50	16776	68286	90543335
Pulmonary arterial pressure increased	31.14	15.91	15	16811	3901	90607720
Wound	30.82	15.91	9	16817	302971	90308650
Exposure during pregnancy	30.70	15.91	4	16822	238406	90373215
Chest pain	30.65	15.91	129	16697	319516	90292105
Atrial flutter	30.42	15.91	21	16805	10737	90600884
Hyperthyroidism	30.31	15.91	26	16800	18284	90593337
Paracentesis	30.10	15.91	10	16816	985	90610636
Chronic obstructive pulmonary disease	29.76	15.91	51	16775	73778	90537843
Cardiorenal syndrome	29.01	15.91	10	16816	1102	90610519
Psoriatic arthropathy	28.99	15.91	4	16822	228331	90383290
Haemoglobin decreased	28.43	15.91	80	16746	161876	90449745
Lower respiratory tract infection	28.30	15.91	6	16820	250653	90360968
Epistaxis	28.20	15.91	54	16772	85071	90526550
Fibromyalgia	27.69	15.91	3	16823	206266	90405355
Pericardial haemorrhage	27.33	15.91	11	16815	1865	90609756
BRASH syndrome	27.31	15.91	11	16815	1868	90609753
Localised oedema	27.28	15.91	16	16810	6178	90605443
Renal disorder	26.65	15.91	34	16792	37825	90573796
Hyponatraemia	26.48	15.91	69	16757	133469	90478152
Chronic left ventricular failure	25.82	15.91	8	16818	630	90610991
Syncope	25.74	15.91	68	16758	132595	90479026
Blood potassium increased	25.62	15.91	25	16801	20724	90590897
Blood cholesterol increased	25.59	15.91	4	16822	208008	90403613
Pleural effusion	25.49	15.91	61	16765	111930	90499691
Bone density decreased	25.45	15.91	23	16803	17322	90594299
International normalised ratio increased	25.01	15.91	37	16789	47279	90564342
Stomatitis	24.76	15.91	10	16816	274688	90336933
Haemodialysis	24.55	15.91	17	16809	8730	90602891
Urticaria	24.21	15.91	14	16812	312720	90298901
Toxic epidermal necrolysis	24.14	15.91	30	16796	32498	90579123
Oxygen saturation decreased	23.88	15.91	58	16768	107425	90504196
Generalised oedema	23.61	15.91	23	16803	19030	90592591
Orthopnoea	23.32	15.91	15	16811	6820	90604801
Dialysis	22.75	15.91	18	16808	11311	90600310
Vascular parkinsonism	21.81	15.91	5	16821	122	90611499
Hypertension	21.79	15.91	32	16794	457500	90154121
Injury	21.71	15.91	5	16821	197344	90414277
Electrocardiogram QT prolonged	21.62	15.91	44	16782	72412	90539209
Liver injury	21.62	15.91	3	16823	170564	90441057
Asthenia	21.54	15.91	171	16655	533580	90078041
Fall	21.48	15.91	158	16668	481652	90129969
Left ventricular failure	21.14	15.91	14	16812	6686	90604935
Anaemia	20.74	15.91	124	16702	352678	90258943
Inflammation	20.72	15.91	4	16822	178588	90433033
Blood aldosterone abnormal	20.52	15.91	4	16822	43	90611578
Abdominal distension	20.50	15.91	62	16764	130539	90481082
Restlessness	20.43	15.91	29	16797	35691	90575930
Impaired healing	20.34	15.91	9	16817	234190	90377431
Device leakage	20.34	15.91	16	16810	9975	90601646
Pulmonary arterial wedge pressure increased	20.28	15.91	6	16820	404	90611217
Respiratory disorder	20.10	15.91	40	16786	64776	90546845
Brain natriuretic peptide increased	20.05	15.91	13	16813	5992	90605629
Respiratory distress	19.93	15.91	30	16796	38916	90572705
Elephantiasis	19.48	15.91	3	16823	6	90611615
Intentional product use issue	19.37	15.91	8	16818	216884	90394737
Hypoaesthesia	19.22	15.91	18	16808	314192	90297429
Oxygen therapy	19.12	15.91	10	16816	3092	90608529
General physical health deterioration	18.76	15.91	23	16803	355092	90256529
Product dose omission issue	18.75	15.91	105	16721	291582	90320039
Nasal congestion	18.51	15.91	45	16781	83369	90528252
Mobility decreased	18.32	15.91	12	16814	250722	90360899
Product use issue	17.82	15.91	21	16805	329898	90281723
Diarrhoea	17.66	15.91	258	16568	938932	89672689
Neutropenia	17.49	15.91	10	16816	224894	90386727
C-reactive protein increased	17.35	15.91	6	16820	181383	90430238
Presyncope	16.99	15.91	25	16801	31780	90579841
Abdominal discomfort	16.87	15.91	40	16786	477288	90134333
Flushing	16.80	15.91	45	16781	88446	90523175
Sepsis	16.77	15.91	72	16754	179742	90431879
Cardiomegaly	16.59	15.91	19	16807	18906	90592715
Transplant evaluation	16.58	15.91	7	16819	1339	90610282
Catheter management	16.50	15.91	9	16817	3027	90608594
Weight increased	16.36	15.91	133	16693	417794	90193827
Hypersensitivity	16.15	15.91	38	16788	454639	90156982
Polyuria	16.10	15.91	14	16812	10026	90601595

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
Cardiac failure congestive	279.20	17.44	223	13023	85379	42522710
Acute kidney injury	172.27	17.44	362	12884	366975	42241114
Hypokalaemia	129.12	17.44	134	13112	71587	42536502
Fluid retention	126.11	17.44	93	13153	31526	42576563
Hypervolaemia	108.25	17.44	75	13171	23050	42585039
Pulmonary hypertension	104.64	17.44	74	13172	23495	42584594
Hypotension	92.56	17.44	229	13017	257402	42350687
Cardiac failure	89.35	17.44	136	13110	106720	42501369
Dyspnoea	79.76	17.44	309	12937	442312	42165777
Right ventricular failure	67.04	17.44	40	13206	9515	42598574
Oedema peripheral	65.49	17.44	136	13110	135940	42472149
Oedema	64.27	17.44	80	13166	51921	42556168
Pulmonary arterial hypertension	62.15	17.44	39	13207	10148	42597941
Blood creatinine increased	56.52	17.44	113	13133	109890	42498199
Off label use	53.00	17.44	73	13173	638262	41969827
Gastrointestinal haemorrhage	50.92	17.44	101	13145	97625	42510464
Drug ineffective	47.51	17.44	77	13169	630120	41977969
Blood potassium increased	47.25	17.44	42	13204	18494	42589595
Renal failure	46.49	17.44	123	13123	143603	42464486
Chronic kidney disease	43.53	17.44	63	13183	47178	42560911
Venous pressure jugular increased	43.18	17.44	14	13232	758	42607331
Dehydration	42.52	17.44	118	13128	141649	42466440
Polyuria	41.12	17.44	30	13216	9981	42598108
Hypovolaemia	39.61	17.44	31	13215	11454	42596635
Hyponatraemia	39.26	17.44	93	13153	101369	42506720
Syncope	38.34	17.44	91	13155	99315	42508774
Generalised oedema	37.60	17.44	34	13212	15302	42592787
Weight increased	34.47	17.44	92	13154	107891	42500198
Death	34.46	17.44	257	12989	470928	42137161
Blood urea increased	33.57	17.44	46	13200	32747	42575342
Necrotising oesophagitis	32.50	17.44	12	13234	959	42607130
Glomerular filtration rate decreased	31.99	17.44	32	13214	16319	42591770
Blood pressure systolic decreased	30.18	17.44	19	13227	4968	42603121
Product use in unapproved indication	29.95	17.44	10	13236	184446	42423643
Blood potassium decreased	27.83	17.44	33	13213	20351	42587738
Cellulitis	27.76	17.44	60	13186	61525	42546564
Transfusion	27.14	17.44	24	13222	10490	42597599
Dizziness	26.79	17.44	150	13096	249104	42358985
Orthopnoea	26.34	17.44	18	13228	5399	42602690
Cardiac failure acute	25.43	17.44	26	13220	13607	42594482
Atrial fibrillation	25.36	17.44	98	13148	139495	42468594
Azotaemia	24.84	17.44	18	13228	5926	42602163
Venous pressure jugular decreased	24.30	17.44	5	13241	41	42608048
Asthenia	23.85	17.44	159	13087	280634	42327455
Brain natriuretic peptide increased	22.75	17.44	18	13228	6752	42601337
Blood loss anaemia	22.72	17.44	21	13225	9715	42598374
Febrile neutropenia	22.57	17.44	15	13231	185688	42422401
Blood sodium decreased	22.51	17.44	28	13218	18134	42589955
Neutropenia	21.80	17.44	18	13228	199413	42408676
Peripheral swelling	21.22	17.44	69	13177	90201	42517888
Burkholderia test positive	21.18	17.44	9	13237	1041	42607048
Urine output decreased	20.76	17.44	21	13225	10852	42597237
Ventricular tachycardia	20.51	17.44	35	13211	30125	42577964
Chronic obstructive pulmonary disease	20.35	17.44	54	13192	63060	42545029
Acute respiratory failure	20.01	17.44	40	13206	38818	42569271
International normalised ratio increased	19.53	17.44	45	13201	48123	42559966
Pain in jaw	19.01	17.44	23	13223	14479	42593610

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
Cardiac failure congestive	533.97	15.11	376	26800	150624	110411499
Hypervolaemia	367.33	15.11	198	26978	49262	110512861
Fluid retention	349.76	15.11	242	26934	94065	110468058
Acute kidney injury	318.26	15.11	563	26613	634867	109927256
Pulmonary arterial hypertension	292.14	15.11	148	27028	32420	110529703
Right ventricular failure	253.57	15.11	125	27051	25829	110536294
Pulmonary hypertension	221.93	15.11	149	27027	55071	110507052
Dyspnoea	216.33	15.11	678	26498	1106194	109455929
Hypokalaemia	186.64	15.11	227	26949	182221	110379902
Death	151.81	15.11	445	26731	698424	109863699
Hypotension	151.52	15.11	371	26805	523478	110038645
Cardiac failure	142.97	15.11	202	26974	187424	110374699
Oedema peripheral	142.17	15.11	274	26902	328386	110233737
Off label use	124.45	15.11	112	27064	1500073	109062050
Renal failure	120.92	15.11	207	26969	226367	110335756
Gastrointestinal haemorrhage	119.91	15.11	174	27002	165344	110396779
Drug ineffective	110.74	15.11	127	27049	1520413	109041710
Chronic kidney disease	100.01	15.11	108	27068	76183	110485940
Atrial fibrillation	99.87	15.11	192	26984	229450	110332673
Acute respiratory failure	99.46	15.11	107	27069	75153	110486970
Oedema	99.33	15.11	182	26994	209794	110352329
Cardiac failure acute	99.17	15.11	66	27110	24012	110538111
Blood creatinine increased	98.74	15.11	168	27008	182721	110379402
Dehydration	84.92	15.11	202	26974	279309	110282814
Dyspnoea exertional	76.19	15.11	110	27066	103950	110458173
Infusion related reaction	74.16	15.11	5	27171	381157	110180966
Blood urea increased	74.13	15.11	79	27097	54878	110507245
Transfusion	73.02	15.11	56	27120	25416	110536707
Blood potassium increased	71.87	15.11	62	27114	33187	110528936
Pulmonary oedema	70.21	15.11	104	27072	100555	110461568
Blood potassium decreased	69.85	15.11	76	27100	54038	110508085
Calcium deficiency	69.20	15.11	21	27155	1161	110560962
Hypoxia	65.98	15.11	116	27060	129399	110432724
Syncope	63.24	15.11	148	27028	202388	110359735
Hyponatraemia	58.34	15.11	150	27026	217503	110344620
Hyperkalaemia	58.32	15.11	113	27063	135683	110426440
Rheumatoid arthritis	58.07	15.11	4	27172	299609	110262514
Generalised oedema	57.90	15.11	53	27123	30651	110531472
Hypovolaemia	54.26	15.11	44	27132	21630	110540493
Polyuria	53.05	15.11	40	27136	17698	110544425
Orthopnoea	52.23	15.11	33	27143	10988	110551135
Metabolic alkalosis	51.82	15.11	26	27150	5569	110556554
Respiratory failure	51.24	15.11	142	27034	215190	110346933
Pain in jaw	51.14	15.11	63	27113	51114	110511009
Maternal exposure during pregnancy	50.58	15.11	3	27173	254880	110307243
Joint swelling	50.21	15.11	23	27153	442822	110119301
Treatment failure	50.14	15.11	5	27171	277229	110284894
Electrolyte imbalance	49.53	15.11	53	27123	36975	110525148
Glomerular filtration rate decreased	48.87	15.11	47	27129	28909	110533214
Cellulitis	48.28	15.11	100	27076	125916	110436207
Systemic lupus erythematosus	47.57	15.11	4	27172	254334	110307789
Arthropathy	47.55	15.11	7	27169	287515	110274608
International normalised ratio increased	47.17	15.11	80	27096	86692	110475431
Chronic left ventricular failure	46.99	15.11	16	27160	1280	110560843
Alopecia	46.16	15.11	16	27160	364737	110197386
Hospitalisation	45.41	15.11	105	27071	142388	110419735
Gout	44.84	15.11	50	27126	36516	110525607
Cardiorenal syndrome	44.43	15.11	17	27159	1901	110560222
Product use in unapproved indication	43.77	15.11	28	27148	447349	110114774
Necrotising oesophagitis	43.70	15.11	16	27160	1584	110560539
BRASH syndrome	42.62	15.11	20	27156	3703	110558420
Torsade de pointes	42.59	15.11	39	27137	22561	110539562
Azotaemia	42.38	15.11	28	27148	10057	110552066
Brain natriuretic peptide increased	42.04	15.11	29	27147	11180	110550943
Neutropenia	41.62	15.11	20	27156	374600	110187523
Musculoskeletal stiffness	41.53	15.11	9	27167	279813	110282310
Pericardial effusion	41.16	15.11	60	27116	57157	110504966
Chronic obstructive pulmonary disease	41.08	15.11	86	27090	109072	110453051
Glossodynia	40.15	15.11	4	27172	222000	110340123
Urine sodium decreased	39.90	15.11	10	27166	269	110561854
Ascites	39.55	15.11	77	27099	92731	110469392
Venous pressure jugular increased	38.71	15.11	14	27162	1338	110560785
Cor pulmonale	38.10	15.11	16	27160	2278	110559845
Urine chloride decreased	37.62	15.11	8	27168	101	110562022
Weight increased	36.44	15.11	201	26975	419443	110142680
Arthralgia	36.11	15.11	87	27089	779545	109782578
Renal impairment	35.09	15.11	114	27062	188331	110373792
Dermatitis exfoliative	34.85	15.11	26	27150	11321	110550802
Left ventricular failure	34.76	15.11	26	27150	11363	110550760
Pericarditis	34.72	15.11	6	27170	219108	110343015
Asthenia	34.56	15.11	288	26888	688711	109873412
Helicobacter infection	33.62	15.11	3	27173	181874	110380249
Atrial flutter	32.93	15.11	35	27141	24227	110537896
Psoriatic arthropathy	32.04	15.11	5	27171	196756	110365367
Oxygen consumption increased	32.00	15.11	19	27157	5666	110556457
Blood cholesterol increased	31.72	15.11	4	27172	184781	110377342
Haemoglobin decreased	31.62	15.11	133	27043	248594	110313529
Chest pain	31.16	15.11	178	26998	376197	110185926
Intentional product use issue	31.14	15.11	11	27165	247895	110314228
Rash	31.05	15.11	101	27075	820863	109741260
Paracentesis	30.97	15.11	12	27164	1388	110560735
Cardiac arrest	30.51	15.11	112	27064	196641	110365482
Blood sodium decreased	30.24	15.11	42	27134	38277	110523846
Blood loss anaemia	29.93	15.11	29	27147	17996	110544127
Contraindicated product administered	29.54	15.11	12	27164	248255	110313868
Cholecystitis	29.37	15.11	34	27142	25848	110536275
Inflammation	29.11	15.11	6	27170	193232	110368891
Oxygen therapy	29.06	15.11	16	27160	4137	110557986
Fall	29.05	15.11	250	26926	603232	109958891
Hepatic enzyme increased	28.83	15.11	22	27154	320870	110241253
Renal disorder	28.73	15.11	47	27129	49432	110512691
Drug hypersensitivity	28.64	15.11	42	27134	454048	110108075
Fibromyalgia	28.62	15.11	4	27172	170905	110391218
Pulmonary arterial pressure increased	28.50	15.11	17	27159	5110	110557013
Febrile neutropenia	28.10	15.11	22	27154	316745	110245378
Epistaxis	28.10	15.11	83	27093	130289	110431834
Discomfort	27.88	15.11	9	27167	214698	110347425
Impaired healing	27.85	15.11	7	27169	196710	110365413
Exposure during pregnancy	27.85	15.11	4	27172	167420	110394703
Drug abuse	27.80	15.11	5	27171	177406	110384717
Urine output decreased	27.55	15.11	29	27147	19847	110542276
C-reactive protein increased	26.81	15.11	10	27166	217909	110344214
Haemodialysis	26.63	15.11	27	27149	17692	110544431
Pleural effusion	26.58	15.11	100	27076	177609	110384514
Stomatitis	26.29	15.11	17	27159	270225	110291898
Lower respiratory tract infection	25.47	15.11	14	27162	243092	110319031
Hypertension	25.13	15.11	55	27121	510029	110052094
Paraesthesia	24.78	15.11	19	27157	276502	110285621
Oxygen saturation decreased	24.03	15.11	89	27087	156893	110405230
Urticaria	23.72	15.11	26	27150	318831	110243292
Localised oedema	23.67	15.11	19	27157	9204	110552919
Dizziness	23.27	15.11	268	26908	697925	109864198
Pericardial haemorrhage	23.18	15.11	15	27161	5202	110556921
Cardiomegaly	23.09	15.11	32	27144	29098	110533025
Mobility decreased	23.00	15.11	15	27161	237407	110324716
Myoclonus	22.86	15.11	34	27142	32964	110529159
General physical health deterioration	22.51	15.11	44	27132	425251	110136872
Drug intolerance	22.45	15.11	41	27135	406471	110155652
Liver injury	21.98	15.11	5	27171	150408	110411715
Venous pressure jugular decreased	21.86	15.11	5	27171	90	110562033
Anaemia	21.46	15.11	217	26959	546869	110015254
Wound	21.14	15.11	16	27160	234421	110327702
Respiratory distress	21.11	15.11	50	27126	68824	110493299
Dialysis	20.98	15.11	25	27151	19594	110542529
Vascular parkinsonism	20.53	15.11	5	27171	119	110562004
Gastrointestinal arteriovenous malformation	20.39	15.11	8	27168	957	110561166
Blood pressure decreased	19.97	15.11	68	27108	115023	110447100
Bone density decreased	19.77	15.11	22	27154	16020	110546103
Catheter management	19.77	15.11	12	27164	3723	110558400
Pulmonary arterial wedge pressure increased	19.66	15.11	7	27169	639	110561484
Ventricular tachycardia	19.51	15.11	40	27136	49969	110512154
Blood aldosterone abnormal	19.40	15.11	4	27172	43	110562080
Blood pressure systolic decreased	19.33	15.11	20	27156	13421	110548702
Multiple organ dysfunction syndrome	19.17	15.11	81	27095	151629	110410494
Hypoaesthesia	18.90	15.11	30	27146	314193	110247930
N-terminal prohormone brain natriuretic peptide increased	18.74	15.11	14	27162	6107	110556016
Abdominal distension	18.03	15.11	88	27088	175015	110387108
Hypovolaemic shock	17.98	15.11	20	27156	14563	110547560
Dizziness postural	17.95	15.11	20	27156	14589	110547534
Elephantiasis	17.78	15.11	3	27173	9	110562114
Bursitis	17.67	15.11	5	27171	129913	110432210
Shock	17.62	15.11	40	27136	53548	110508575
Peripheral swelling	17.17	15.11	163	27013	403871	110158252
Tricuspid valve incompetence	17.11	15.11	25	27151	23848	110538275
Malignant neoplasm progression	16.95	15.11	11	27165	174556	110387567
Mental status changes	16.91	15.11	49	27127	76073	110486050
Dyspnoea at rest	16.90	15.11	15	27161	8331	110553792
Prothrombin time prolonged	16.84	15.11	21	27155	17240	110544883
Night sweats	16.72	15.11	6	27170	133977	110428146
Presyncope	16.65	15.11	37	27139	48850	110513273
Condition aggravated	16.59	15.11	263	26913	734573	109827550
Nasal congestion	16.12	15.11	57	27119	98225	110463898
Congestive hepatopathy	16.12	15.11	12	27164	5208	110556915
Unevaluable event	16.03	15.11	41	27135	59186	110502937
Melaena	15.99	15.11	45	27131	68712	110493411
Hyperthyroidism	15.92	15.11	27	27149	29234	110532889
Respiratory disorder	15.90	15.11	46	27130	71336	110490787
Hypersensitivity	15.73	15.11	49	27127	403949	110158174
White blood cell count decreased	15.67	15.11	20	27156	229370	110332753
Gastrointestinal disorder	15.61	15.11	22	27154	241930	110320193
Waist circumference increased	15.60	15.11	8	27168	1793	110560330
Liver disorder	15.17	15.11	8	27168	142235	110419888

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C03BA08	CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, EXCL. THIAZIDES Sulfonamides, plain
ATC	C03EA12	CARDIOVASCULAR SYSTEM DIURETICS DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION Low-ceiling diuretics and potassium-sparing agents
FDA PE	N0000175359	Increased Diuresis
FDA EPC	N0000175420	Thiazide-like Diuretic
MeSH PA	D000959	Antihypertensive Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D004232	Diuretics
MeSH PA	D045283	Natriuretic Agents
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D049993	Sodium Chloride Symporter Inhibitors
CHEBI has role	CHEBI:35498	diuretic
CHEBI has role	CHEBI:35554	cardiovascular drug
CHEBI has role	CHEBI:35674	antihypertensive agent
CHEBI has role	CHEBI:50184	ion transport inhibitor

Related Drugs by ATC class:

C03BA Sulfonamides, plain 10 drugs

chlortalidone clofenamide clopamide clorexolone fenquizone indapamide mefruside meticrane quinethazone xipamide

C03EA Low-ceiling diuretics and potassium-sparing agents 9 drugs

altizide bendroflumethiazide butizide chlortalidone cyclopenthiazide epitizide hydrochlorothiazide mebutizide trichlormethiazide

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

Disease	Relation	SNOMED_ID	DOID
Hypertensive disorder	indication	38341003	DOID:10763
Renal Disease with Edema	indication
Peripheral Edema due to Chronic Heart Failure	indication
Pulmonary Edema due to Chronic Heart Failure	indication
Anuria	contraindication	2472002	DOID:2983
Hypercholesterolemia	contraindication	13644009
Hepatic encephalopathy	contraindication	13920009	DOID:13413
Orthostatic hypotension	contraindication	28651003
Hypokalemia	contraindication	43339004
Pregnancy-induced hypertension	contraindication	48194001
Systemic lupus erythematosus	contraindication	55464009	DOID:9074
Sympathectomy	contraindication	57071006
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Hypercalcemia	contraindication	66931009	DOID:12678
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Oliguria	contraindication	83128009
Hyponatremia	contraindication	89627008
Gout	contraindication	90560007	DOID:13189
Hypomagnesemia	contraindication	190855004
Persistent vomiting	contraindication	196746003
Acute pancreatitis	contraindication	197456007	DOID:2913
Severe diarrhea	contraindication	409587002
Azotemia	contraindication	445009001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.66	acidic
pKa2	1.3	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			CHEMBL	CHEMBL
Solute carrier family 12 member 1	Transporter	Q13621	S12A1_HUMAN		Kd	8.45	WOMBAT-PK
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN		Ki	5.70	CHEMBL
Carbonic anhydrase 7	Enzyme	P43166	CAH7_HUMAN		Ki	8.68	CHEMBL

External reference:

ID	Source
D00431	KEGG_DRUG
4018161	VANDF
C0025854	UMLSCUI
CHEBI:64354	CHEBI
CHEMBL878	ChEMBL_ID
DB00524	DRUGBANK_ID
D008788	MESH_DESCRIPTOR_UI
4170	PUBCHEM_CID
4838	IUPHAR_LIGAND_ID
2627	INN_ID
TZ7V40X7VX	UNII
203794	RXNORM
1440	MMSL
47402	MMSL
5101	MMSL
d00299	MMSL
002310	NDDF
22198003	SNOMEDCT_US
387123003	SNOMEDCT_US
TZ7V40X7VX	INXIGHT DRUGS

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0185-0055	TABLET	5 mg	ORAL	ANDA	23 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0185-5050	TABLET	2.50 mg	ORAL	ANDA	23 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0185-5600	TABLET	10 mg	ORAL	ANDA	23 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6172	TABLET	2.50 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6173	TABLET	5 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6174	TABLET	10 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7328	TABLET	2.50 mg	ORAL	ANDA	12 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7329	TABLET	5 mg	ORAL	ANDA	12 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7520	TABLET	2.50 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7521	TABLET	5 mg	ORAL	ANDA	22 sections
METOLAZONE	HUMAN PRESCRIPTION DRUG LABEL	1	10135-765	TABLET	2.50 mg	ORAL	ANDA	22 sections
METOLAZONE	HUMAN PRESCRIPTION DRUG LABEL	1	10135-766	TABLET	5 mg	ORAL	ANDA	22 sections
METOLAZONE	HUMAN PRESCRIPTION DRUG LABEL	1	10135-767	TABLET	10 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	42571-416	TABLET	2.50 mg	ORAL	ANDA	21 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	42571-417	TABLET	5 mg	ORAL	ANDA	21 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	42571-418	TABLET	10 mg	ORAL	ANDA	21 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	43353-890	TABLET	2.50 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	43353-931	TABLET	5 mg	ORAL	ANDA	24 sections
METOLAZONE	Human Prescription Drug Label	1	46708-532	TABLET	2.50 mg	ORAL	ANDA	22 sections
METOLAZONE	Human Prescription Drug Label	1	46708-533	TABLET	5 mg	ORAL	ANDA	22 sections
METOLAZONE	Human Prescription Drug Label	1	46708-534	TABLET	10 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	48433-068	TABLET	2.50 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	48433-069	TABLET	5 mg	ORAL	ANDA	24 sections
Metolazone	Human Prescription Drug Label	1	50090-6802	TABLET	2.50 mg	ORAL	ANDA	12 sections
METOLAZONE	HUMAN PRESCRIPTION DRUG LABEL	1	50090-6972	TABLET	2.50 mg	ORAL	ANDA	23 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	50742-349	TABLET	2.50 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	50742-350	TABLET	5 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	50742-351	TABLET	10 mg	ORAL	ANDA	22 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	51079-023	TABLET	2.50 mg	ORAL	ANDA	24 sections
Metolazone	HUMAN PRESCRIPTION DRUG LABEL	1	51079-024	TABLET	5 mg	ORAL	ANDA	24 sections

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metolazone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Description:

Drug dosage:

ADMET properties:

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Approvals:

FDA Adverse Event Reporting System (Female)

FDA Adverse Event Reporting System (Male)

FDA Adverse Event Reporting System (Geriatric)

FDA Adverse Event Reporting System (Pediatric)

Pharmacologic Action:

Related Drugs by ATC class:

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

🐶 Veterinary Drug Use

🐶 Veterinary products

Acid dissociation constants calculated using MoKa v3.0.0

Orange Book patent data (new drug applications)

Orange Book exclusivity data (new drug applications)

Bioactivity Summary:

External reference:

Pharmaceutical products: