metolazone

Trade name: zaroxolyn

Small moleculeapproved

Approved

Nov 27, 1973

Metolazone is a thiazide-like diuretic marketed under the brand names Mykrox and Zaroxolyn. Zaroxolyn is indicated for the treatment of salt and water retention including: • Edema accompanying congestive heart failure; • Edema accompanying renal diseases including the nephrotic syndrome and states of diminished renal function. Zaroxolyn is also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. 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. — NCATS

Clinical trial activity

25 trials · 33 clinical orgs · 24 marketing orgs

Phase 1
4
Phase 2
7
Phase 3
2
Phase 4
9

Earliest trial started Dec 1, 2002 (NCT00649051)

Timeline

1970s

  1. Nov 27, 1973

    Earliest FDA Approval

  2. Nov 27, 1973

    Lannett Company, Inc. — NDA Secondary Org

  3. Nov 27, 1973

    I3 Pharms — Marketing Organization

  4. Nov 27, 1973

    I3 Pharms — NDA Secondary Org

1980s

  1. Feb 24, 1981

    G D Searle — NDA Secondary Org

  2. Oct 30, 1987

    Chartwell Pharmaceuticals — Marketing Organization

  3. Oct 30, 1987

    Chartwell Pharmaceuticals — NDA Secondary Org

2000s

  1. Jan 1, 2002

    Mylan — Earliest Phase 1 Sponsor(trial)

  2. Dec 19, 2003

    Sandoz — Marketing Organization

  3. Dec 19, 2003

    Novartis — Marketing Organization

  4. Dec 23, 2003

    Mylan — Marketing Organization

  5. Dec 24, 2003

    Teva — Marketing Organization

  6. Jan 6, 2004

    Ani Pharmaceuticals — Marketing Organization

  7. Apr 29, 2004

    Roxane Laboratories — Marketing Organization

  8. Apr 29, 2004

    Boehringer Ingelheim — Marketing Organization

  9. Jul 21, 2004

    Watson Pharmaceuticals — Marketing Organization

2010s

  1. Jan 1, 2014

    Earliest Phase 2 Sponsor(trial)

  2. Jan 1, 2019

    Earliest Phase 3 Sponsor(trial)

2020s

  1. Dec 2, 2020

    Alembic — Marketing Organization

  2. Mar 30, 2021

    Bayshore Pharms Llc — Marketing Organization

  3. Mar 30, 2021

    Innogenix — Marketing Organization

  4. Mar 30, 2021

    IPCA Laboratories Ltd. — Marketing Organization

  5. Mar 30, 2021

    Unichem — Marketing Organization

  6. Aug 20, 2021

    Rubicon Research — Marketing Organization

  7. Oct 24, 2022

    Renata — Marketing Organization

  8. Oct 25, 2022

    AACE PHARMS — Marketing Organization

  9. Oct 25, 2022

    Nephron Pharmaceuticals Corporation — Marketing Organization

  10. Apr 17, 2024

    Leading Pharma Llc — Marketing Organization

  11. Nov 6, 2024

    Micro Labs Ltd India — Marketing Organization

Indications

Mechanism of action

Approval history

  • approvedNov 27, 1973

Chemistry & pharmacology

Loading structure…

SMILES

CC1NC2=C(C=C(C(Cl)=C2)S(N)(=O)=O)C(=O)N1C3=CC=CC=C3C
Mol. weight
365.835 g/mol
Lipinski Ro5
Pass
Rule of 3
No
Chirality
Racemic Mixture
Inorganic
No
Polymer
No
Delivery
Oral
Availability
Prescription Only

Oral

Yes

Parenteral

No

Topical

No

Black box warning

Sources

Also known as

  • 2-methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone
  • 2-methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone
  • 7-chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide
  • 7-chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide
  • 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide
  • 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide
  • diulo
  • diulo
  • metenix
  • metenix
  • metolazon
  • metolazon
  • metolazona
  • metolazona
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • metolazone
  • métolazone
  • métolazone
  • metolazonum
  • metolazonum
  • metozalone
  • mykrox
  • mykrox
  • sr72022
  • sr72022
  • sr72022
  • sr72022
  • sr72022
  • sr72022
  • sr-720-22
  • sr-720-22
  • xuret
  • xuret
  • zaroloxyn
  • zaroxolyn
  • zaroxolyn
  • zaroxolyn
  • zaroxolyn

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT07199088N/AOct 11, 2025University of Health Sciences Lahore
NCT06414759Phase 4Jul 1, 2024Cairo University, Misr International University, National Heart Institute, Egypt
NCT06326112Phase 2May 1, 2024Canadian Institutes of Health Research (CIHR), Unity Health Toronto
NCT06273397N/AMay 1, 2024Clinica Alemana de Santiago
NCT06166654Phase 4Apr 1, 2024University of Copenhagen
NCT05986773Phase 4Oct 10, 2023Ospedale Regionale di Lugano, Stadtspital Zürich
NCT05904808Phase 4Apr 19, 2023Technion University
NCT04860011Phase 3Apr 27, 2021University of Glasgow
NCT04542304Phase 2Oct 31, 2020Stanford University
NCT04438213Phase 2Jul 31, 2020Merck, Yale University
NCT04163588Phase 3Oct 1, 2019Policlinico Casilino, University of Roma La Sapienza, Vita-Salute University of Milano. Italy
NCT03746002Phase 4Jan 1, 2019University of Maryland
NCT03574857Phase 4Jun 30, 2018University of Virginia
NCT02606253Phase 4Feb 1, 2016Vanderbilt University
NCT02646540Phase 1Jan 1, 2016Emory University
NCT02620384Phase 2Jul 1, 2015Aultman Health Foundation
NCT05633758Phase 2Mar 31, 2014Scripps
NCT02047422N/AJan 1, 2014Yonsei University
NCT01817803N/AMar 1, 2013Yonsei University
NCT01617798N/AJun 1, 2012Oregon Health and Science University
Showing 20 of 25 trials
Page 1 / 2

Organizations

Research & Development (33)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
MylanFor profit3312002
Kendle International Inc.For profit2012003
Yonsei UniversityAcademic/Hospital2212013
Aultman Health FoundationAcademic/Hospital1112015
Cairo UniversityAcademic/Hospital1112024
Canadian Institutes of Health Research (CIHR)Academic/Hospital1012024
Clinica Alemana de SantiagoAcademic/Hospital1112024
Emory UniversityAcademic/Hospital1112016
MerckFor profit1012020
Misr International UniversityAcademic/Hospital1012024
National Heart Institute, EgyptGovernment1012024
Oregon Health and Science UniversityAcademic/Hospital1112012
Ospedale Regionale di LuganoAcademic/Hospital1012023
Policlinico CasilinoAcademic/Hospital1112019
PRACSFor profit1012002
ScrippsAcademic/Hospital1112014
Stadtspital ZürichAcademic/Hospital1112023
Stanford UniversityAcademic/Hospital1112020
Technion UniversityAcademic/Hospital1112023
Unity Health TorontoAcademic/Hospital1112024
33 organizations
Page 1 / 2

Marketing (29)

OrganizationOrg typeRelationshipDate
AACE PHARMSFor profitMKTGOct 25, 2022
AlembicFor profitMKTGDec 2, 2020
AlembicFor profitSYNDec 2, 2020
Ani PharmaceuticalsFor profitSYNDec 24, 2003
Ani PharmaceuticalsFor profitMKTGJan 6, 2004
Bayshore Pharms LlcFor profitMKTGMar 30, 2021
Boehringer IngelheimFor profitMKTGApr 29, 2004
Chartwell PharmaceuticalsFor profitMKTGOct 30, 1987
Chartwell PharmaceuticalsFor profitNDA2Oct 30, 1987
FisonsFor profitNDA
G D SearleFor profitNDA2Feb 24, 1981
I3 PharmsFor profitMKTGNov 27, 1973
I3 PharmsFor profitNDA2Nov 27, 1973
IPCA Laboratories Ltd.For profitMKTGMar 30, 2021
InnogenixFor profitMKTGMar 30, 2021
Lannett Company, Inc.For profitNDA2Nov 27, 1973
Leading Pharma LlcFor profitMKTGApr 17, 2024
Micro Labs Ltd IndiaFor profitMKTGNov 6, 2024
MylanFor profitMKTGDec 23, 2003
Nephron Pharmaceuticals CorporationFor profitMKTGOct 25, 2022
NovartisFor profitMKTGDec 19, 2003
RenataFor profitMKTGOct 24, 2022
Roxane LaboratoriesFor profitMKTGApr 29, 2004
Rubicon ResearchFor profitMKTGAug 20, 2021
Rubicon ResearchFor profitSYNAug 20, 2021
SandozFor profitMKTGDec 19, 2003
TevaFor profitMKTGDec 24, 2003
UnichemFor profitMKTGMar 30, 2021
Watson PharmaceuticalsFor profitMKTGJul 21, 2004