metolazone Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Hosey CM, Chan R, 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

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
Fluid retention 233.40 15.80 171 16215 50875 46618801
Cardiac failure congestive 232.18 15.80 218 16168 91532 46578144
Fluid overload 211.71 15.80 127 16259 27058 46642618
Pulmonary arterial hypertension 188.70 15.80 116 16270 25812 46643864
Right ventricular failure 187.56 15.80 98 16288 15995 46653681
Dyspnoea 125.07 15.80 430 15956 515118 46154558
Pulmonary hypertension 123.92 15.80 102 16284 35891 46633785
Drug ineffective 112.59 15.80 49 16337 677789 45991887
Oedema 104.22 15.80 123 16263 66948 46602728
Oedema peripheral 94.88 15.80 187 16199 159519 46510157
Acute kidney injury 93.69 15.80 235 16151 235620 46434056
Renal failure 69.80 15.80 135 16251 113459 46556217
Rheumatoid arthritis 57.65 15.80 8 16378 240207 46429469
Hypokalaemia 55.75 15.80 106 16280 87918 46581758
Cardiac failure 54.03 15.80 99 16287 79849 46589827
Electrolyte imbalance 53.44 15.80 46 16340 17180 46652496
Off label use 53.16 15.80 34 16352 379807 46289869
Dyspnoea exertional 52.71 15.80 76 16310 50213 46619463
Gastrointestinal haemorrhage 51.26 15.80 95 16291 77278 46592398
Cardiac failure acute 48.42 15.80 32 16354 8046 46661630
Acute respiratory failure 46.14 15.80 54 16332 29084 46640592
BRASH syndrome 45.98 15.80 10 16376 96 46669580
Hypoxia 45.32 15.80 72 16314 51766 46617910
Pulmonary oedema 44.71 15.80 71 16315 51034 46618642
Gout 42.90 15.80 34 16352 11322 46658354
Death 41.43 15.80 229 16157 335319 46334357
Atrial fibrillation 40.75 15.80 103 16283 103487 46566189
Hyperkalaemia 39.69 15.80 67 16319 50642 46619034
Ascites 39.37 15.80 56 16330 36528 46633148
Chronic kidney disease 38.84 15.80 59 16327 40812 46628864
Hospitalisation 38.48 15.80 75 16311 63310 46606366
Cor pulmonale 38.36 15.80 17 16369 1926 46667750
Transfusion 38.36 15.80 34 16352 13197 46656479
Blood potassium decreased 37.67 15.80 56 16330 38007 46631669
Urine chloride decreased 36.67 15.80 8 16378 78 46669598
Calcium deficiency 36.03 15.80 13 16373 860 46668816
Weight increased 34.24 15.80 131 16255 164342 46505334
Respiratory failure 32.92 15.80 90 16296 94726 46574950
Torsade de pointes 32.80 15.80 30 16356 12124 46657552
Urine sodium decreased 31.16 15.80 8 16378 164 46669512
Blood urea increased 30.57 15.80 41 16345 25311 46644365
Metabolic alkalosis 30.40 15.80 16 16370 2644 46667032
Hypotension 30.17 15.80 161 16225 232428 46437248
Arthralgia 28.42 15.80 53 16333 364550 46305126
Blood creatinine increased 28.00 15.80 74 16312 76329 46593347
Oxygen consumption increased 25.63 15.80 16 16370 3647 46666029
Chest pain 25.60 15.80 126 16260 176198 46493478
Infusion related reaction 25.14 15.80 3 16383 101205 46568471
Cardiorenal syndrome 24.72 15.80 9 16377 611 46669065
Neutropenia 24.17 15.80 10 16376 143194 46526482
Generalised oedema 23.31 15.80 27 16359 14372 46655304
Renal impairment 23.26 15.80 68 16318 74304 46595372
Pain in jaw 22.78 15.80 45 16341 38327 46631349
Rash 22.67 15.80 58 16328 356454 46313222
Pericardial haemorrhage 22.61 15.80 11 16375 1540 46668136
Atrial flutter 21.66 15.80 21 16365 9127 46660549
Pericardial effusion 21.66 15.80 35 16351 25508 46644168
Cholecystitis 21.56 15.80 26 16360 14440 46655236
Dermatitis exfoliative 21.34 15.80 17 16369 5699 46663977
Dehydration 21.04 15.80 111 16275 159429 46510247
Paracentesis 21.04 15.80 9 16377 936 46668740
Localised oedema 20.93 15.80 16 16370 5053 46664623
Alopecia 20.73 15.80 16 16370 162398 46507278
Joint swelling 20.39 15.80 17 16369 166056 46503620
Device leakage 20.12 15.80 16 16370 5349 46664327
Brain natriuretic peptide increased 19.91 15.80 15 16371 4635 46665041
Multiple organ dysfunction syndrome 19.88 15.80 51 16335 51659 46618017
Pulmonary arterial pressure increased 19.48 15.80 13 16373 3319 46666357
Therapeutic product effect decreased 19.21 15.80 3 16383 82598 46587078
Packed red blood cell transfusion 19.17 15.80 11 16375 2152 46667524
Vascular parkinsonism 19.10 15.80 5 16381 111 46669565
Orthopnoea 18.84 15.80 16 16370 5864 46663812
Cardiac arrest 18.78 15.80 72 16314 90327 46579349
Pulmonary arterial wedge pressure increased 18.50 15.80 6 16380 287 46669389
Dialysis 18.13 15.80 20 16366 10096 46659580
Oxygen therapy 17.96 15.80 10 16376 1847 46667829
International normalised ratio increased 17.77 15.80 46 16340 46837 46622839
Respiratory disorder 17.41 15.80 33 16353 27267 46642409
Condition aggravated 17.38 15.80 146 16240 244906 46424770
Blood potassium increased 16.83 15.80 25 16361 16942 46652734
Oxygen saturation decreased 16.83 15.80 58 16328 69106 46600570
Hypertension 16.67 15.80 27 16359 196329 46473347
Chronic obstructive pulmonary disease 16.42 15.80 51 16335 57582 46612094
Azotaemia 16.37 15.80 13 16373 4338 46665338
Cellulitis 16.29 15.80 58 16328 70230 46599446

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 276.91 16.02 253 12596 84154 29855475
Acute kidney injury 152.83 16.02 351 12498 273491 29666138
Hypokalaemia 125.73 16.02 130 12719 50062 29889567
Fluid retention 112.43 16.02 90 12759 24908 29914721
Pulmonary hypertension 90.87 16.02 71 12778 18965 29920664
Cardiac failure 85.82 16.02 139 12710 83279 29856350
Hypotension 84.01 16.02 231 12618 200334 29739295
Fluid overload 67.78 16.02 60 12789 19032 29920597
Oedema 63.49 16.02 85 12764 42908 29896721
Oedema peripheral 58.93 16.02 136 12713 105696 29833933
Chronic kidney disease 54.63 16.02 74 12775 37764 29901865
Pulmonary arterial hypertension 53.95 16.02 39 12810 9262 29930367
Dyspnoea 53.28 16.02 282 12567 333013 29606616
Blood creatinine increased 50.38 16.02 117 12732 91258 29848371
Renal failure 50.35 16.02 145 12704 128821 29810808
Right ventricular failure 45.03 16.02 33 12816 8003 29931626
Blood urea increased 38.80 16.02 57 12792 31324 29908305
Weight increased 38.10 16.02 93 12756 74820 29864809
Drug ineffective 36.67 16.02 56 12793 340331 29599298
Polyuria 36.47 16.02 28 12821 7278 29932351
Hyponatraemia 34.78 16.02 84 12765 67118 29872511
Febrile neutropenia 34.67 16.02 3 12846 106690 29832939
Dehydration 34.60 16.02 124 12725 123415 29816214
Hypovolaemia 34.49 16.02 29 12820 8576 29931053
Necrotising oesophagitis 34.31 16.02 11 12838 413 29939216
Generalised oedema 31.90 16.02 32 12817 11853 29927776
Syncope 28.87 16.02 91 12758 84812 29854817
Gastrointestinal haemorrhage 27.97 16.02 89 12760 83357 29856272
Asthenia 27.84 16.02 176 12673 221114 29718515
Blood potassium decreased 27.78 16.02 35 12814 16627 29923002
Off label use 25.85 16.02 42 12807 249248 29690381
Transfusion 25.58 16.02 23 12826 7438 29932191
Cellulitis 24.75 16.02 59 12790 46725 29892904
Blood chloride decreased 24.44 16.02 17 12832 3796 29935833
Blood sodium decreased 24.38 16.02 32 12817 15824 29923805
Orthopnoea 23.99 16.02 18 12831 4522 29935107
Brain natriuretic peptide increased 23.58 16.02 17 12832 4018 29935611
Chronic obstructive pulmonary disease 21.06 16.02 55 12794 46071 29893558
Atrial fibrillation 21.05 16.02 97 12752 108027 29831602
Pulmonary oedema 19.63 16.02 52 12797 43923 29895706
Ventricular tachycardia 19.54 16.02 36 12813 23826 29915803
Neutropenia 19.40 16.02 16 12833 128524 29811105
Condition aggravated 18.77 16.02 112 12737 137754 29801875
Pain in jaw 17.87 16.02 24 12825 12132 29927497
Product use in unapproved indication 17.42 16.02 5 12844 73688 29865941
Renal injury 17.00 16.02 23 12826 11706 29927923
International normalised ratio increased 16.97 16.02 52 12797 47687 29891942
Azotaemia 16.45 16.02 15 12834 4937 29934692
Interstitial lung disease 16.39 16.02 3 12846 60194 29879435
Acute respiratory failure 16.34 16.02 35 12814 25815 29913814

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 D049990 Membrane Transport Modulators
MeSH PA D045283 Natriuretic Agents
MeSH PA D049993 Sodium Chloride Symporter Inhibitors
CHEBI has role CHEBI:35498 diuretics
CHEBI has role CHEBI:35674 antihypertensive
CHEBI has role CHEBI:50184 ion-transport inhibitors

Drug Use (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

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 7 Enzyme Ki 8.68 CHEMBL

External reference:

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

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 0527-2215 TABLET 2.50 mg ORAL NDA AUTHORIZED GENERIC 24 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 0527-2216 TABLET 5 mg ORAL NDA AUTHORIZED GENERIC 24 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 0527-2217 TABLET 10 mg ORAL NDA AUTHORIZED GENERIC 24 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 0904-6915 TABLET 5 mg ORAL NDA authorized generic 24 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 0904-6916 TABLET 2.50 mg ORAL NDA authorized generic 24 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 43353-999 TABLET 2.50 mg ORAL NDA AUTHORIZED GENERIC 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 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
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 54868-5056 TABLET 5 mg ORAL ANDA 23 sections
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 54868-5104 TABLET 2.50 mg ORAL ANDA 23 sections
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 54868-5119 TABLET 10 mg ORAL ANDA 23 sections
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 60687-536 TABLET 2.50 mg ORAL NDA authorized generic 25 sections
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 60687-547 TABLET 5 mg ORAL NDA authorized generic 25 sections
METOLAZONE Human Prescription Drug Label 1 62332-532 TABLET 2.50 mg ORAL ANDA 22 sections
METOLAZONE Human Prescription Drug Label 1 62332-533 TABLET 5 mg ORAL ANDA 22 sections
METOLAZONE Human Prescription Drug Label 1 62332-534 TABLET 10 mg ORAL ANDA 22 sections
Metolazone HUMAN PRESCRIPTION DRUG LABEL 1 63629-7875 TABLET 5 mg ORAL ANDA 23 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 65580-643 TABLET 2.50 mg ORAL NDA AUTHORIZED GENERIC 24 sections
metolazone HUMAN PRESCRIPTION DRUG LABEL 1 65580-644 TABLET 5 mg ORAL NDA AUTHORIZED GENERIC 24 sections