Chemical: Drug
chlorthalidone

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


1. FDA Label for chlorthalidone

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Cardiovascular Diseases
    • Indications & usage section, Warnings section
    • source: PHONT
  • Death
    • Precautions section
    • source: PHONT
  • Heart Failure
    • Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Hypertension
    • Indications & usage section, Warnings section, Precautions section
    • source: PHONT
  • Myocardial Infarction
    • Warnings section, Precautions section
    • source: PHONT

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for chlorthalidone

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs11122576 NC_000001.10:g.230846679T>C, NC_000001.11:g.230710933T>C, NG_008836.1:g.8658A>G, NM_000029.3:c.-3-80A>G, rs58482950, rs59792559
T > C
SNP
No VIP available CA No Variant Annotations available
rs12143842 NC_000001.10:g.162033890C>T, NC_000001.11:g.162064100C>T, rs59411707
C > T
SNP
rs1799752 NC_000017.10:g.61565890_61565891insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.10:g.61565890_61565891insG, NC_000017.11:g.63488529_63488530insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.11:g.63488529_63488530insG, NG_011648.1:g.16457_16458insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NG_011648.1:g.16457_16458insG, NM_000789.3:c.2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_000789.3:c.2306-119_2306-118insG, NM_001178057.1:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_001178057.1:c.584-119_584-118insG, NM_152830.2:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_152830.2:c.584-119_584-118insG, XM_005257110.1:c.1757-119_1757-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_005257110.1:c.1757-119_1757-118insG, XM_006721737.2:c.644-119_644-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_006721737.2:c.644-119_644-118insG
- > ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
- > G
indel
No VIP available CA VA
rs200148 NC_000006.11:g.143345696G>A, NC_000006.12:g.143024559G>A, NR_038987.1:n.595-2606C>T, rs61230468, rs629392
G > A
SNP
No VIP available CA VA
rs3025058 NC_000011.9:g.102715948_102715949insA, NG_012100.1:g.3394_3395insT, NM_002422.4:c.-1672_-1671insT, NW_003871077.1:g.13452_13453insA, rs144886253, rs61423715, rs66847152, rs66847153, rs72520913, rs72562167
- > A
indel
No VIP available CA VA
rs4291 NC_000017.10:g.61554194T>A, NC_000017.11:g.63476833T>A, NG_011648.1:g.4761T>A, NM_000789.3:c.-262T>A, XM_005257110.1:c.-717T>A
T > A
SNP
No VIP available CA VA
rs5065 NC_000001.10:g.11906068A>G, NC_000001.11:g.11846011A>G, NG_012926.1:g.6773T>C, NM_006172.3:c.454T>C, NP_006163.1:p.Ter152Arg, NR_037806.1:n.1479+245A>G, rs1130764, rs17413194, rs17856153, rs198363, rs3189984, rs57081035
A > G
SNP
*152R
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Chlorothalidone
  • Chlorphthalidolone
  • Chlorphthalidone
  • Chlortalidone
  • Chlorthalidon
  • Clodronic Acid
Trade Names
  • Higroton
  • Hydro-Long
  • Hygroton
  • Igroton
  • Isoren
  • Natriuran
  • Oradil
  • Phthalamodine
  • Phthalamudine
  • Renon
  • Saluretin
  • Tenoretic
  • Thalitone
  • Zambesil
Brand Mixture Names
  • Tenoretic (chlorthalidone + atenolol)

PharmGKB Accession Id

PA448970

Type(s):

Drug

Description

A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic.

Source: Drug Bank

Indication

For management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Chlorthalidone inhibits sodium ion transport across the renal tubular epithelium in the cortical diluting segment of the ascending limb of the loop of Henle. By increasing the delivery of sodium to the distal renal tubule, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism.

Source: Drug Bank

Pharmacology

Chlorthalidone, a monosulfonamyl diuretic, differs form other thiazide diuretics in that a double ring system is incorporated into its structure. Chlorthalidone is used alone or with atenolol in the management of hypertension and edema.

Source: Drug Bank

Food Interaction

Take with food (increases availability).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Liver

Source: Drug Bank

Protein Binding

High (75% 58% to albumin)

Source: Drug Bank

Absorption

Absorbed relatively rapidly after oral administration.

Source: Drug Bank

Half-Life

40 hours

Source: Drug Bank

Toxicity

Symptoms of overdose include nausea, weakness, dizziness and disturbances of electrolyte balance.

Source: Drug Bank

Route of Elimination

The major portion of the drug is excreted unchanged by the kidneys.

Source: Drug Bank

Chemical Properties

Chemical Formula

C14H11ClN2O4S

Source: Drug Bank

Isomeric SMILES

c1ccc2c(c1)C(=O)NC2(c3ccc(c(c3)S(=O)(=O)N)Cl)O

Source: OpenEye

Canonical SMILES

NS(=O)(=O)C1=C(Cl)C=CC(=C1)C1(O)NC(=O)C2=CC=CC=C12

Source: Drug Bank

Average Molecular Weight

338.766

Source: Drug Bank

Monoisotopic Molecular Weight

338.012805247

Source: Drug Bank

SMILES

NS(=O)(=O)C1=C(Cl)C=CC(=C1)C1(O)NC(=O)C2=CC=CC=C12

Source: Drug Bank

InChI String

InChI=1S/C14H11ClN2O4S/c15-11-6-5-8(7-12(11)22(16,20)21)14(19)10-4-2-1-3-9(10)13(18)17-14/h1-7,19H,(H,17,18)(H2,16,20,21)

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
ACE
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ADD1
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
AGT
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
MMP3
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
NPPA
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SCNN1A

Drug Targets

Gene Description
SLC12A1 (source: Drug Bank)

Drug Interactions

Interaction Description
chlorthalidone - amantadine The diuretic increases the adverse effects of amantadine (source: Drug Bank)
chlorthalidone - deslanoside Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone - diazoxide Significant hyperglycemic effect (source: Drug Bank)
chlorthalidone - diazoxide Significant hyperglycemic effect (source: Drug Bank)
chlorthalidone - digitoxin Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone - digitoxin Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone - digoxin Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone - digoxin Possible electrolyte variations and arrhythmias (source: Drug Bank)
chlorthalidone - dofetilide Increased risk of cardiotoxicity and arrythmias (source: Drug Bank)
chlorthalidone - dofetilide Increased risk of cardiotoxicity and arrythmias (source: Drug Bank)
chlorthalidone - lithium The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
chlorthalidone - lithium The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
digoxin - chlorthalidone Possible electrolyte variations and arrhythmias (source: Drug Bank)
digoxin - chlorthalidone Possible electrolyte variations and arrhythmias (source: Drug Bank)
lithium - chlorthalidone The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
lithium - chlorthalidone The thiazide diuretic increases serum levels of lithium (source: Drug Bank)
tenoxicam - chlorthalidone Tenoxicam may antagonize the blood pressure lowering effect of Chlorthalidone. Monitor for changes in the therapeutic effect of Chlorthalidone if Tenoxicam is initiated, discontinued or dose changed. (source: Drug Bank)
trandolapril - chlorthalidone The thiazide diuretic, Chlorthalidone, may increase the hypotensive effect of Trandolapril. Chlorthalidone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy. (source: Drug Bank)
treprostinil - chlorthalidone Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to chlorthalidone: 8

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic effects of 'candidate gene complexes' on stroke in the GenHAT study. Pharmacogenetics and genomics. 2014. Sørensen Izel F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Alteration in fasting glucose after prolonged treatment with a thiazide diuretic. Diabetes research and clinical practice. 2014. Karnes Jason H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The effects of angiotensinogen gene polymorphisms on cardiovascular disease outcomes during antihypertensive treatment in the GenHAT study. Frontiers in pharmacology. 2014. Do Anh N, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study. Stroke; a journal of cerebral circulation. 2011. Sherva Richard, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic association of hypertension candidate genes with fasting glucose in the GenHAT Study. Journal of hypertension. 2010. Irvin Marguerite R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension. JAMA : the journal of the American Medical Association. 2008. Lynch Amy I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study. The pharmacogenomics journal. 2007. Davis B R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005. Arnett Donna K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0179-0015-01
DrugBank:
DB00310
ChEBI:
3654
KEGG Drug:
D00272
PubChem Compound:
2732
PubChem Substance:
149435
46505541
Drugs Product Database (DPD):
360279
BindingDB:
25900
ChemSpider:
2631
Therapeutic Targets Database:
DAP000521
FDA Drug Label at DailyMed:
49ef8384-946d-43cb-b9be-f174e789d7dc

Clinical Trials

These are trials that mention chlorthalidone and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.