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Gerald Chi
 
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There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
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===Acute Overdose===
 
====Signs and Symptoms====
 
* Description
 
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|drugBox=
 
{{drugbox2
| IUPAC_name = 7-chloro-2-methyl-3-(2-methylphenyl)- 4-oxo-1,2-dihydroquinazoline-6-sulfonamide
| IUPAC_name = 7-chloro-2-methyl-3-(2-methylphenyl)- 4-oxo-1,2-dihydroquinazoline-6-sulfonamide
| image = Metolazone structure_svg.png
| image = Metolazone structure_svg.png
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| excretion = primarily urine
| excretion = primarily urine
}}
}}
{{CMG}}


<!--Mechanism of Action-->
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*
<!--Structure-->
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*
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Pharmacodynamics-->


{{SI}}
|PD=


==[[Metolazone (patient information)|For patient information, click here]]==
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


==Overview==
<!--Pharmacokinetics-->
:''[[Metaxalone]], a muscle relaxant, is a medicine with a similar name.''
'''Metolazone''' is a [[thiazide diuretic]] marketed under the brand names '''Zaroxolyn''' and '''Mykrox'''. It is primarily used to treat [[congestive heart failure]] and [[hypertension|high blood pressure]]. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the [[kidney]], so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with [[loop diuretic]]s such as [[furosemide]] or [[bumetanide]], but these highly effective combinations can lead to [[dehydration]] and [[Electrolyte disturbance|electrolyte abnormalities]].


==History==
|PK=
Metolazone was developed in the 1970s. Its creator, Indian physician Dr. B. Vithal Shetty, has been active in helping the U.S. [[Food and Drug Administration]] review drug applications, and in the development of new medicines.<ref name="FDA">Katague, David B. "Chemistry Reviewer Still in Lab". ''News Along the Pike'' (newsletter of the [[Food and Drug Administration]]' s Center for Drug Evaluation and Research). Volume 2, Issue 10. [http://www.fda.gov/cder/pike/nov96.pdf PDF]. Accessed on January 25, 2006.</ref>
Metolazone quickly gained popularity due to its lower renal toxicity compared to other diuretics (especially thiazides) in patients with [[renal insufficiency]].


==Structure==
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
Metolazone is a [[quinazoline]], a derivative of the similar diuretic [[quinethazone]], as well as a [[sulfonamide]]. It is related to analogs of 1,2,4-benzothiadizine-1,1-dioxide ([[benzothiadiazine]]). These drugs are called ''benzothiadiazides'', or ''thiazides'' for short. Chemically, metolazone is not a substituted benzothiadiazine, and therefore is not technically a [[thiazide]]. However, since metolazone, as well other drugs like [[indapamide]], act on the same target as thiazides and behave in a similar pharmacologic fashion, they are considered "thiazide-like diuretics". Therefore, they are often included in the thiazide diuretics despite not being thiazides themselves.<ref name="G&G">*Jackson, Edwin K. "Diuretics". In ''[[Goodman & Gilman's The Pharmacological Basis of Therapeutics]]'', 11th ed., edited by Laurence L. Brunton et al. New York: McGraw-Hill, 2006.</ref>


==Mechanism of action==
<!--Nonclinical Toxicology-->
[[Image:Kidney nephron.png|thumb|left|250px|Schematic of a [[nephron]]. The [[distal convoluted tubule]] is labelled "2nd convoluted tubule" (the [[proximal convoluted tubule]] is the first) in this illustration.]]


The primary target of all thiazide diuretics, including metolazone, is the [[distal convoluted tubule]], part of the [[nephron]] in the [[kidney]], where they inhibit the [[sodium-chloride symporter]].
|nonClinToxic=


In the kidney, blood is filtered into the [[lumen]], or open space, of the nephron tubule. Whatever remains in the tubule will travel to the [[urinary bladder|bladder]] as [[urine]] and eventually be excreted. The cells lining the tubule modify the fluid inside, absorbing some material and excreting others. One side of the cell (the ''apical'' side) faces the lumen; the opposite side (the ''basolateral'' side) faces the interstitial space near blood vessels. The other sides are tightly joined to neighboring cells.
There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.


As with other regions, tubule cells in the distal convoluted tubule possess the [[adenosine triphosphate|ATP]]-powered [[sodium]]-[[potassium]] [[antiporter]] ([[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup>-ATPase]]), which uses energy from ATP to transfer three sodium ions out from the basolateral surface (toward [[blood vessel]]s) while simultaneously transferring two potassium ions in. The distal convoluted tubule cells also possess a [[sodium-chloride symporter]] on the apical side, which passively allows one sodium ion and one chloride ion to diffuse together in from the lumen (where urine is forming) into the cell interior. As sodium is pumped out of the cell by the ATPase, its intracellular concentration falls, and additional sodium begins to diffuse in from the tubule lumen as replacement. The symporter requires chloride to be transported in as well. Water passively follows to maintain [[isotonic]]ity; excess chloride and potassium passively diffuse out the cell through basolateral channels into the interstitial space, and water accompanies them. The water and chloride, as well as the sodium pumped out by the ATPase, will be absorbed into the bloodstream.
<!--Clinical Studies-->


Metolazone and the other thiazide diuretics inhibit the function of the sodium-chloride symporter, preventing sodium and chloride, and therefore water too, from leaving the lumen to enter the tubule cell. As a result, water remains in the lumen and is excreted as urine, instead of being reabsorbed into the bloodstream. Since most of the sodium in the lumen has already been reabsorbed by the time the filtrate reaches the distal convoluted tubule, thiazide diuretics have limited effects on water balance and on electrolyte levels.<ref name="G&G" /> Nevertheless, they can be associated with [[hyponatremia|low sodium levels]], [[volume depletion]], and [[hypotension|low blood pressure]], among other adverse effects.
|clinicalStudies=


==Pharmacodynamics==
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
Metolazone is only available in [[tablet|oral]] preparations. Approximately 65% of the amount ingested becomes available in the bloodstream. Its [[half-life]] is approximately fourteen hours, similar to indapamide but considerably longer than [[hydrochlorothiazide]]. Metolazone is around ten times as potent as hydrochlorothiazide. The primary form of excretion is in the urine (around 80%); the remaining fifth is evenly split between [[bile|biliary]] excretion and metabolism into inactive forms.<ref name="G&G" />


==Use==
=====Condition1=====
One of the primary uses of metolazone is for treating [[edema]] (fluid retention) associated with [[congestive heart failure]] (CHF). In mild heart failure, metolazone or another diuretic may be used alone, or combined with other diuretics for moderate or severe heart failure. In addition to preventing fluid buildup, the use of metolazone may allow the patient to relax the amount of sodium restriction that is required. Although most thiazide diuretics lose their effectiveness in [[renal failure]], metolazone retains active even when the [[glomerular filtration rate]] (GFR) is below 30&ndash;40 mL/min (moderate renal failure). This gives it a considerable advantage over other thiazide diuretics, since renal and heart failure often coexist and contribute to fluid retention.<ref name="Harrison's">Braunwald, Eugene. "Heart Failure and Cor Pulmonale". In ''[[Harrison's Principles of Internal Medicine]]'', 15th ed., edited by Dennis L. Kasper et al. New York: McGraw-Hill, 2005.</ref>


Metolazone may also be used in renal (kidney) disease, such as [[chronic renal failure]] or the [[nephrotic syndrome]]. Chronic renal failure causes excess fluid retention that is often treated with [[diet (nutrition)|diet]] adjustments and diuretics<ref name="Harrison's" /> Metolazone may be combined with other diuretics (typically loop diuretics) to treat diuretic resistance in CHF, chronic renal failure, and nephrotic syndrome.<ref name="CDT">Rosenberg J, Gustafsson F, Galatius S, & Hildebrandt PR. "Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature." ''Cardiovascular Drugs and Therapy''. 2005 Aug;19(4):301-6. PMID 16189620.</ref> Metolazone and a loop diuretic will synergistically enhance diuresis over the use of either agent alone. Using this combination, diuretic effects will occur at two different segments of the nephron; namely, the loop diuretic will act at the [[loop of Henle]], and metolazone will act at the distal convoluted tubule. Metolazone is frequently prescribed in addition to the loop diuretic. Metolazone may be used for edema caused by liver [[cirrhosis]] as well.
* Description


The other major use of metolazone is in treating [[hypertension]] (high blood pressure). Thiazide diuretics, though usually not metolazone, are very often used alone as first-line treatment for mild hypertension. They are also used in combination with other drugs for difficult-to-treat or more severe hypertension. "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" (JNC 7) recommends thiazide diuretics as the initial medication for treatment of hypertension. [[Hydrochlorothiazide]] is by far the most commonly used, as it is both better-studied and cheaper (about four times) than metolazone, although as mentioned above metolazone is used in patients with moderate renal failure.<ref name="G&G" />
<!--How Supplied-->


==Toxicity==
|howSupplied=
Since thiazide diuretics affect the transport of [[electrolyte]]s and water in the kidney, they can be responsible for abnormalities of water balance and electrolyte levels. Removal of too much fluid can cause [[volume depletion]] and [[hypotension]]. Various electrolyte abnormalities may result, including [[hyponatremia]] (low sodium), [[hypokalemia]] (low potassium), [[hypochloremia]] (low chloride), [[hypomagnesemia]] (low [[magnesium]]), [[hypercalcemia]] (high [[calcium]]), and [[hyperuricemia]] (high [[uric acid]]). These may result in [[dizziness]], [[headache]], or heart [[arrhythmia]]s (palpitations).<ref name="G&G" /> Serious, though rare, side effects include [[aplastic anemia]], [[pancreatitis]], [[agranulocytosis]], and [[angioedema]]. Metolazone, like other thiazide diuretics, may unmask latent [[diabetes mellitus]] or exacerbate [[gout]], especially by interacting with medicines used to treat gout. In addition, thiazide diuretics, including metalozone, are [[sulfonamide]]s; those with hypersensitivity to sulfonamides ("sulfa allergy") should not use them.<ref name="G&G" />


==References==
*  
{{reflist|2}}
:*http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4170. Accessed on January 25, 2006.
:*http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD01109.txt. Accessed on January 25, 2006.
:*http://www.ijp-online.com/article.asp?issn=0253-7613;year=1974;volume=6;issue=1;spage=40;epage=53;aulast=Vithal;type=0. Accessed on January 25, 2006.
:*http://www.centaurpharma.com/pdf/news/metolaz-scrip.pdf [PDF]. Accessed on January 25, 2006.


<!--Patient Counseling Information-->


{{Antihypertensives and diuretics}}
|fdaPatientInfo=
 
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
 
<!--Precautions with Alcohol-->
 
|alcohol=
 
 
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
 
<!--Brand Names-->
 
|brandNames=
 
* ®<ref>{{Cite web | title =  | url =  }}</ref>
 
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|lookAlike=
 
* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>
 
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<!--Category-->


[[Category:Thiazides]]
[[Category:Cardiovascular Drugs]]
[[Category:Drugs]]
[[Category:Drug]]
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Revision as of 20:22, 5 July 2014

Metolazone
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

Disclaimer

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Black Box Warning

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Metolazone is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition1
  • Dosing Information
  • Dosage
Condition2
  • Dosing Information
  • Dosage
Condition3
  • Dosing Information
  • Dosage
Condition4
  • Dosing Information
  • Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Metolazone in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Metolazone in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Metolazone in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Metolazone in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Metolazone in pediatric patients.

Contraindications

  • Condition1

Warnings

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Metolazone in the drug label.

Central Nervous System
Cardiovascular
Respiratory
Gastrointestinal
Hypersensitivity
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Metolazone in the drug label.

Central Nervous System
Cardiovascular
Respiratory
Gastrointestinal
Hypersensitivity
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Metolazone in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Metolazone during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Metolazone with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Metolazone with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Metolazone with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Metolazone with respect to specific gender populations.

Race

There is no FDA guidance on the use of Metolazone with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Metolazone in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Metolazone in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Metolazone in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Metolazone in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Metolazone in the drug label.

Condition1
  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Metolazone in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Metolazone in the drug label.

Pharmacology

Template:Px
Metolazone
Systematic (IUPAC) name
7-chloro-2-methyl-3-(2-methylphenyl)- 4-oxo-1,2-dihydroquinazoline-6-sulfonamide
Identifiers
CAS number 17560-51-9
ATC code C03BA08
PubChem 4170
DrugBank APRD01109
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 365.835 g/mol
Pharmacokinetic data
Bioavailability ~65%
Metabolism minimal
Half life 14 hours
Excretion primarily urine
Therapeutic considerations
Pregnancy cat.

B

Legal status

Prescription only

Routes Oral

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Metolazone in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Metolazone in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Metolazone in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Metolazone in the drug label.

Condition1
  • Description

How Supplied

Storage

There is limited information regarding Metolazone Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Metolazone |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Metolazone |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Metolazone in the drug label.

Precautions with Alcohol

  • Alcohol-Metolazone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)


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