Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C16H15ClN3O3S.Na |
| Molecular Weight | 387.816 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CC1NC2=CC(Cl)=C(C=C2C(=O)N1C3=C(C)C=CC=C3)S([NH-])(=O)=O
InChI
InChIKey=IWCGZZSHDMZBQR-UHFFFAOYSA-M
InChI=1S/C16H16ClN3O3S.Na/c1-9-5-3-4-6-14(9)20-10(2)19-13-8-12(17)15(24(18,22)23)7-11(13)16(20)21;/h3-8,10H,1-2H3,(H3,18,19,21,22,23);/q;+1/p-1
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | ZAROXOLYN Approved UseMetolazone tablets USP are 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. Metolazone tablets USP are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. Mykrox® tablets, a more rapidly available form of metolazone, are intended for the treatment of new patients with mild to moderate hypertension. A dose titration is necessary if Mykrox® tablets are to be substituted for Zaroxolyn® tablets and other formulations of metolazone that share its slow and incomplete bioavailability, in the treatment of hypertension. Usage In Pregnancy The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequence of pregnancy. Metolazone tablets USP are indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (see PRECAUTIONS). Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may be appropriate. Launch Date1973 |
|||
| Primary | ZAROXOLYN Approved UseMetolazone tablets USP are 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. Metolazone tablets USP are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. Mykrox® tablets, a more rapidly available form of metolazone, are intended for the treatment of new patients with mild to moderate hypertension. A dose titration is necessary if Mykrox® tablets are to be substituted for Zaroxolyn® tablets and other formulations of metolazone that share its slow and incomplete bioavailability, in the treatment of hypertension. Usage In Pregnancy The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequence of pregnancy. Metolazone tablets USP are indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (see PRECAUTIONS). Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may be appropriate. Launch Date1973 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
8.225 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29145890 |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
METOLAZONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3.63 ng/mL DRUG LABEL http://products.sanofi.ca/en/zaroxolyn.pdf |
2.5 mg 1 times / day unknown, oral dose: 2.5 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
METOLAZONE unknown | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
50.51 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29145890 |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
METOLAZONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
99.74 ng × h/mL DRUG LABEL http://products.sanofi.ca/en/zaroxolyn.pdf |
2.5 mg 1 times / day unknown, oral dose: 2.5 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
METOLAZONE unknown | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.47 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29145890 |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
METOLAZONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.5% DRUG LABEL http://products.sanofi.ca/en/zaroxolyn.pdf |
2.5 mg 1 times / day unknown, oral dose: 2.5 mg route of administration: Oral experiment type: UNKNOWN co-administered: |
METOLAZONE unknown | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
150 mg single, oral Highest studied dose Dose: 150 mg Route: oral Route: single Dose: 150 mg Sources: Page: p.197 |
unhealthy, 18, 19 n = 2 Health Status: unhealthy Condition: Chronic renal failure Age Group: 18, 19 Sex: M+F Population Size: 2 Sources: Page: p.197 |
|
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Edema Sources: |
Disc. AE: Hyponatremia, Hypokalemia... AEs leading to discontinuation/dose reduction: Hyponatremia (severe) Sources: Hypokalemia (severe) |
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Edema Sources: Page: p.3 |
Disc. AE: Azotemia, Hyperuricemia... AEs leading to discontinuation/dose reduction: Azotemia Sources: Page: p.3Hyperuricemia |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypokalemia | severe Disc. AE |
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Edema Sources: |
| Hyponatremia | severe Disc. AE |
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Edema Sources: |
| Azotemia | Disc. AE | 20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Edema Sources: Page: p.3 |
| Hyperuricemia | Disc. AE | 20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Edema Sources: Page: p.3 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Severe electrolyte disturbances associated with metolazone and furosemide. | 1978 Apr |
|
| Excessive potassium depletion with metolazone and furosemide. | 1983 Jul-Aug |
|
| Use of a bioassay in healthy men to evaluate diuretic-spironolactone combinations. | 1983 May |
|
| Case report: metolazone-associated hypercalcemia and acute pancreatitis. | 1991 Oct |
|
| Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. | 2002 |
|
| Risk factors for the development and progression of dyslipidemia after heart transplantation. | 2002 Apr 27 |
|
| Diuretic resistance predicts mortality in patients with advanced heart failure. | 2002 Jul |
|
| Functional expression of mutations in the human NaCl cotransporter: evidence for impaired routing mechanisms in Gitelman's syndrome. | 2002 Jun |
|
| Metolazone and its role in edema management. | 2003 Mar-Apr |
|
| FI-chemiluminometric study of thiazides by on-line photochemical reaction. | 2004 Nov 19 |
|
| [The place of diuretics in the treatment of chronic heart failure. Part I]. | 2005 |
|
| Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. | 2005 Aug |
|
| Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation. | 2005 Aug |
|
| How much responsibility should heart failure nurses take? | 2005 Mar 16 |
|
| Determination of metolazone in human blood by liquid chromatography with electrospray ionization tandem mass spectrometry. | 2007 Jan 1 |
|
| The evaluation of the diuretic action of parenteral formulations of metolazone. | 2007 Jan-Feb |
|
| Premenstrual syndrome. | 2007 May 1 |
|
| Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited--old leads for new applications? | 2008 Jul 21 |
|
| Role of SLC12A10.2, a Na-Cl cotransporter-like protein, in a Cl uptake mechanism in zebrafish (Danio rerio). | 2009 May |
|
| Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
|
| Characterizing environmental and phenotypic associations using information theory and electronic health records. | 2009 Sep 17 |
|
| Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010 Dec |
|
| Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
Patents
Sample Use Guides
Usual Adult Dose for Hypertension
Initial dose: 2.5 mg orally once a day (Zaroxolyn) or
0.5 mg orally once a day (Mykrox).
Usual Adult Dose for Edema
Initial dose: 5 mg orally once a day (Zaroxolyn) or
0.5 mg orally once a day (Mykrox).
Route of Administration:
Oral
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50869-23-3
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91667967
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Q3AVC19UXB
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ACTIVE MOIETY
SUBSTANCE RECORD
