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

Stem definitionDrug idCAS RN
1783 17560-51-9

Description:

MoleculeDescription

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:

DoseUnitRoute
5 mg O

ADMET properties:

PropertyValueReference
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):

PropertyDescriptionValueUnitConfidenceSimilarity
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:

DateAgencyCompanyOrphan
Nov. 27, 1973 FDA UCB INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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
chlortalidoneclofenamideclopamideclorexolonefenquizoneindapamidemefrusidemeticranequinethazonexipamide
C03EA Low-ceiling diuretics and potassium-sparing agents 9 drugs
altizidebendroflumethiazidebutizidechlortalidonecyclopenthiazideepitizidehydrochlorothiazidemebutizidetrichlormethiazide

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

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Solute carrier family 12 member 3 Transporter INHIBITOR CHEMBL CHEMBL
Solute carrier family 12 member 1 Transporter Kd 8.45 WOMBAT-PK
Carbonic anhydrase 2 Enzyme Ki 5.70 CHEMBL
Carbonic anhydrase 7 Enzyme Ki 8.68 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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