metolazone
Trade name: zaroxolyn
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
Earliest trial started Dec 1, 2002 (NCT00649051)
Timeline
1970s
- Nov 27, 1973
Earliest FDA Approval
- Nov 27, 1973
Lannett Company, Inc. — NDA Secondary Org
- Nov 27, 1973
I3 Pharms — Marketing Organization
- Nov 27, 1973
I3 Pharms — NDA Secondary Org
1980s
- Feb 24, 1981
G D Searle — NDA Secondary Org
- Oct 30, 1987
Chartwell Pharmaceuticals — Marketing Organization
- Oct 30, 1987
Chartwell Pharmaceuticals — NDA Secondary Org
2000s
- Jan 1, 2002
- Dec 19, 2003
Sandoz — Marketing Organization
- Dec 19, 2003
Novartis — Marketing Organization
- Dec 23, 2003
Mylan — Marketing Organization
- Dec 24, 2003
Teva — Marketing Organization
- Jan 6, 2004
Ani Pharmaceuticals — Marketing Organization
- Apr 29, 2004
Roxane Laboratories — Marketing Organization
- Apr 29, 2004
Boehringer Ingelheim — Marketing Organization
- Jul 21, 2004
Watson Pharmaceuticals — Marketing Organization
2020s
- Dec 2, 2020
Alembic — Marketing Organization
- Mar 30, 2021
Bayshore Pharms Llc — Marketing Organization
- Mar 30, 2021
Innogenix — Marketing Organization
- Mar 30, 2021
IPCA Laboratories Ltd. — Marketing Organization
- Mar 30, 2021
Unichem — Marketing Organization
- Aug 20, 2021
Rubicon Research — Marketing Organization
- Oct 24, 2022
Renata — Marketing Organization
- Oct 25, 2022
AACE PHARMS — Marketing Organization
- Oct 25, 2022
Nephron Pharmaceuticals Corporation — Marketing Organization
- Apr 17, 2024
Leading Pharma Llc — Marketing Organization
- Nov 6, 2024
Micro Labs Ltd India — Marketing Organization
Indications
Approved for
Studied for
- Body Fluids · Phase 4
- Cardiomyopathies · Phase 1
- Cardiovascular Diseases · Phase 4
- Critical Illness · Phase 2
- Diuretics · Phase 4
- Edema · Phase 4
- Healthy Volunteers · Phase 1
- Heart Failure, Systolic · Phase 4
- Kidney Failure, Chronic · Phase 2
- Pharmacology · Phase 4
- Renal Insufficiency, Chronic · Phase 2
- Sepsis · Phase 2
- Severe Acute Respiratory Syndrome · Phase 2
- Wounds and Injuries · Phase 2
Mechanism of action
SLC12A3 inhibitor
Approval history
- approvedNov 27, 1973
Chemistry & pharmacology
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
Sources
- WikipediaMetolazone ↗
- NCATSTZ7V40X7VX ↗
- ChEMBLCHEMBL878 ↗
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 ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07199088 | N/A | Oct 11, 2025 | University of Health Sciences Lahore |
| NCT06414759 | Phase 4 | Jul 1, 2024 | Cairo University, Misr International University, National Heart Institute, Egypt |
| NCT06326112 | Phase 2 | May 1, 2024 | Canadian Institutes of Health Research (CIHR), Unity Health Toronto |
| NCT06273397 | N/A | May 1, 2024 | Clinica Alemana de Santiago |
| NCT06166654 | Phase 4 | Apr 1, 2024 | University of Copenhagen |
| NCT05986773 | Phase 4 | Oct 10, 2023 | Ospedale Regionale di Lugano, Stadtspital Zürich |
| NCT05904808 | Phase 4 | Apr 19, 2023 | Technion University |
| NCT04860011 | Phase 3 | Apr 27, 2021 | University of Glasgow |
| NCT04542304 | Phase 2 | Oct 31, 2020 | Stanford University |
| NCT04438213 | Phase 2 | Jul 31, 2020 | Merck, Yale University |
| NCT04163588 | Phase 3 | Oct 1, 2019 | Policlinico Casilino, University of Roma La Sapienza, Vita-Salute University of Milano. Italy |
| NCT03746002 | Phase 4 | Jan 1, 2019 | University of Maryland |
| NCT03574857 | Phase 4 | Jun 30, 2018 | University of Virginia |
| NCT02606253 | Phase 4 | Feb 1, 2016 | Vanderbilt University |
| NCT02646540 | Phase 1 | Jan 1, 2016 | Emory University |
| NCT02620384 | Phase 2 | Jul 1, 2015 | Aultman Health Foundation |
| NCT05633758 | Phase 2 | Mar 31, 2014 | Scripps |
| NCT02047422 | N/A | Jan 1, 2014 | Yonsei University |
| NCT01817803 | N/A | Mar 1, 2013 | Yonsei University |
| NCT01617798 | N/A | Jun 1, 2012 | Oregon Health and Science University |
Organizations
Research & Development (33)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Mylan | For profit | 3 | 3 | 1 | 2002 |
| Kendle International Inc. | For profit | 2 | 0 | 1 | 2003 |
| Yonsei University | Academic/Hospital | 2 | 2 | 1 | 2013 |
| Aultman Health Foundation | Academic/Hospital | 1 | 1 | 1 | 2015 |
| Cairo University | Academic/Hospital | 1 | 1 | 1 | 2024 |
| Canadian Institutes of Health Research (CIHR) | Academic/Hospital | 1 | 0 | 1 | 2024 |
| Clinica Alemana de Santiago | Academic/Hospital | 1 | 1 | 1 | 2024 |
| Emory University | Academic/Hospital | 1 | 1 | 1 | 2016 |
| Merck | For profit | 1 | 0 | 1 | 2020 |
| Misr International University | Academic/Hospital | 1 | 0 | 1 | 2024 |
| National Heart Institute, Egypt | Government | 1 | 0 | 1 | 2024 |
| Oregon Health and Science University | Academic/Hospital | 1 | 1 | 1 | 2012 |
| Ospedale Regionale di Lugano | Academic/Hospital | 1 | 0 | 1 | 2023 |
| Policlinico Casilino | Academic/Hospital | 1 | 1 | 1 | 2019 |
| PRACS | For profit | 1 | 0 | 1 | 2002 |
| Scripps | Academic/Hospital | 1 | 1 | 1 | 2014 |
| Stadtspital Zürich | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Stanford University | Academic/Hospital | 1 | 1 | 1 | 2020 |
| Technion University | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Unity Health Toronto | Academic/Hospital | 1 | 1 | 1 | 2024 |
Marketing (29)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| AACE PHARMS | For profit | MKTG | Oct 25, 2022 |
| Alembic | For profit | MKTG | Dec 2, 2020 |
| Alembic | For profit | SYN | Dec 2, 2020 |
| Ani Pharmaceuticals | For profit | SYN | Dec 24, 2003 |
| Ani Pharmaceuticals | For profit | MKTG | Jan 6, 2004 |
| Bayshore Pharms Llc | For profit | MKTG | Mar 30, 2021 |
| Boehringer Ingelheim | For profit | MKTG | Apr 29, 2004 |
| Chartwell Pharmaceuticals | For profit | MKTG | Oct 30, 1987 |
| Chartwell Pharmaceuticals | For profit | NDA2 | Oct 30, 1987 |
| Fisons | For profit | NDA | — |
| G D Searle | For profit | NDA2 | Feb 24, 1981 |
| I3 Pharms | For profit | MKTG | Nov 27, 1973 |
| I3 Pharms | For profit | NDA2 | Nov 27, 1973 |
| IPCA Laboratories Ltd. | For profit | MKTG | Mar 30, 2021 |
| Innogenix | For profit | MKTG | Mar 30, 2021 |
| Lannett Company, Inc. | For profit | NDA2 | Nov 27, 1973 |
| Leading Pharma Llc | For profit | MKTG | Apr 17, 2024 |
| Micro Labs Ltd India | For profit | MKTG | Nov 6, 2024 |
| Mylan | For profit | MKTG | Dec 23, 2003 |
| Nephron Pharmaceuticals Corporation | For profit | MKTG | Oct 25, 2022 |
| Novartis | For profit | MKTG | Dec 19, 2003 |
| Renata | For profit | MKTG | Oct 24, 2022 |
| Roxane Laboratories | For profit | MKTG | Apr 29, 2004 |
| Rubicon Research | For profit | MKTG | Aug 20, 2021 |
| Rubicon Research | For profit | SYN | Aug 20, 2021 |
| Sandoz | For profit | MKTG | Dec 19, 2003 |
| Teva | For profit | MKTG | Dec 24, 2003 |
| Unichem | For profit | MKTG | Mar 30, 2021 |
| Watson Pharmaceuticals | For profit | MKTG | Jul 21, 2004 |