Identification

Name
Indapamide
Accession Number
DB00808  (APRD01031)
Type
Small Molecule
Groups
Approved
Description

A benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the mechanism is comparable. [PubChem]

Structure
Thumb
Synonyms
  • Indapamid
  • Indapamida
  • Indapamide
  • Indapamidum
  • Metindamide
External IDs
RHC 2555 / S 1520 / SE 1520 / USV 2555
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IndapamideTablet2.5 mgOralSanis Health IncNot applicableNot applicableCanada
IndapamideTablet2.5 mgOralSanis Health Inc2015-10-14Not applicableCanada
IndapamideTablet1.25 mgOralSanis Health Inc2015-10-14Not applicableCanada
Indapamide Hemihydrate 1.25mg - TabTablet1.25 mgOralProval Pharma Division Of Servier Canada Inc1997-08-142012-02-13Canada
Indapamide Hemihydrate Tab 2.5mgTablet2.5 mgOralProval Pharma Division Of Servier Canada Inc1995-12-312012-02-13Canada
Indapamide-2.5Tablet2.5 mgOralPro Doc Limitee1997-04-302008-07-04Canada
LozideTablet2.5 mgOralServier1982-12-31Not applicableCanada
LozideTablet1.25 mgOralServier1995-12-31Not applicableCanada
LozolTablet, film coated1.25 mg/1OralSanofi-Aventis U.S. LLC (formerly known as Aventis Pharmaceuticals Inc.)1983-07-062007-10-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-indapamide 1.25 Mg TabletsTablet1.25 mgOralApotex Corporation2002-11-08Not applicableCanada
Apo-indapamide 2.5mg TabletsTablet2.5 mgOralApotex Corporation1996-10-02Not applicableCanada
Dom-indapamide Tablets 1.25mgTablet1.25 mgOralDominion Pharmacal1999-09-15Not applicableCanada
Dom-indapamide Tablets 2.5mgTablet2.5 mgOralDominion Pharmacal1999-09-15Not applicableCanada
IndapamideTablet, film coated2.5 mg/1OralMylan Pharmaceuticals1996-03-28Not applicableUs
IndapamideTablet, film coated1.25 mg/1OralALPHAPHARM PTY LTD2010-01-012013-01-01Us
IndapamideTablet, film coated1.25 mg/1OralPhysicians Total Care, Inc.2005-03-022014-04-09Us
IndapamideTablet, film coated2.5 mg/1OralA-S Medication Solutions1996-03-28Not applicableUs
IndapamideTablet, film coated2.5 mg/1OralIVAX Pharmaceuticals, Inc.1995-07-272007-05-19Us
IndapamideTablet, film coated1.25 mg/1OralActavis Pharma Company2007-01-02Not applicableUs00228 2597 96 nlmimage10 573b2bb9
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Apo-perindopril-indapamideIndapamide (0.625 mg) + Perindopril erbumine (2 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
Apo-perindopril-indapamideIndapamide (2.5 mg) + Perindopril erbumine (8 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
Apo-perindopril-indapamideIndapamide (1.25 mg) + Perindopril erbumine (4 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
Arcosyl PlusIndapamide (1.25 mg) + Perindopril arginine (5.0 mg)TabletOralServierNot applicableNot applicableCanada
Arcosyl PlusIndapamide (2.5 mg) + Perindopril arginine (10.0 mg)TabletOralServierNot applicableNot applicableCanada
Arcosyl Plus LdIndapamide (0.625 mg) + Perindopril arginine (2.5 mg)TabletOralServierNot applicableNot applicableCanada
Coversyl PlusIndapamide (1.25 mg) + Perindopril erbumine (4 mg)TabletOralServier2002-12-19Not applicableCanada
Coversyl PlusIndapamide (1.25 mg) + Perindopril erbumine (8 mg)TabletOralServierNot applicableNot applicableCanada
Coversyl Plus HdIndapamide (2.5 mg) + Perindopril erbumine (8.0 mg)TabletOralServier2009-05-07Not applicableCanada
Coversyl Plus LdIndapamide (0.625 mg) + Perindopril erbumine (2 mg)TabletOralServier2003-05-16Not applicableCanada
International/Other Brands
Arifon (Servier) / Bajaten (Merck) / Fludex (Servier) / Indamol (Teofarma) / Ipamix (Visufarma) / Lozide (Servier) / Lozol (sanofi-aventis) / Natrilix (Servier) / Natrix (Kyoto Yakuhin) / Noranat (Sandoz) / Tandix (Azevedos) / Tertensif (Servier) / Veroxil (Baldacci)
Categories
UNII
F089I0511L
CAS number
26807-65-8
Weight
Average: 365.835
Monoisotopic: 365.06008979
Chemical Formula
C16H16ClN3O3S
InChI Key
NDDAHWYSQHTHNT-UHFFFAOYSA-N
InChI
InChI=1S/C16H16ClN3O3S/c1-10-8-11-4-2-3-5-14(11)20(10)19-16(21)12-6-7-13(17)15(9-12)24(18,22)23/h2-7,9-10H,8H2,1H3,(H,19,21)(H2,18,22,23)
IUPAC Name
4-chloro-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)-3-sulfamoylbenzamide
SMILES
CC1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O

Pharmacology

Indication

For the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.

Associated Conditions
Pharmacodynamics

Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.

Mechanism of action

Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2.

TargetActionsOrganism
ASolute carrier family 12 member 3
inhibitor
Human
Absorption

Rapidly absorbed from gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

71-79%

Metabolism

Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.

Route of elimination

Indapamide is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.

Half life

14 hours (biphasic)

Clearance
Not Available
Toxicity

Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Indapamide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe serum concentration of Indapamide can be increased when it is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Indapamide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Indapamide.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Indapamide.
1alpha-Hydroxyvitamin D5The risk or severity of hypercalcemia can be increased when Indapamide is combined with 1alpha-Hydroxyvitamin D5.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Indapamide.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Indapamide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Indapamide.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Indapamide.
6-Deoxyerythronolide BThe metabolism of Indapamide can be decreased when combined with 6-Deoxyerythronolide B.
Food Interactions
  • Take without regard to meals. Magnesium, potassium and zinc needs increased.

References

Synthesis Reference

Chunyi Yeh, Yi-Lung Wang, Ya-Sheng Yang, Ya-Ching Chang Chein, "Oral sustained-release pharmaceutical composition of indapamide, production and use thereof." U.S. Patent US20060182803, issued August 17, 2006.

US20060182803
General References
  1. Dong DL, Wang QH, Yue P, Jiao JD, Gu RM, Yang BF: Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84. Epub 2006 Mar 2. [PubMed:16556441]
  2. Lukasz Komsta, Monika Waksmundzka-Hajnos, Joseph Sherma (2014). Thin Layer Chromatography in Drug Analysis. Taylor & Francis.
  3. Thiazide Diruetics in Hypertension- European Journal of Cardiology [Link]
  4. Significant Drug–Drug Interactions with Antineoplastics [Link]
External Links
Human Metabolome Database
HMDB0014946
KEGG Drug
D00345
PubChem Compound
3702
PubChem Substance
46508626
ChemSpider
3574
BindingDB
25901
ChEBI
5893
ChEMBL
CHEMBL406
Therapeutic Targets Database
DAP000498
PharmGKB
PA449975
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Indapamide
ATC Codes
C03BA11 — IndapamideG01AE10 — Combinations of sulfonamidesC09BX01 — Perindopril, amlodipine and indapamide
AHFS Codes
  • 40:28.24 — Thiazide-like Diuretics
FDA label
Download (322 KB)
MSDS
Download (72.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentCalcium Phosphate Kidney Stones1
3Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3RecruitingPreventionAcute Intracerebral Haemorrhage (ICH) / High Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)2
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Impaired Renal Function1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentArterial Hypertension2
Not AvailableCompletedDiagnosticArterial Hypertension1
Not AvailableNot Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Cadista pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Sanofi aventis us llc
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Alphapharm Party Ltd.
  • Amerisource Health Services Corp.
  • Arcola Laboratories
  • A-S Medication Solutions LLC
  • Caremark LLC
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Heartland Repack Services LLC
  • Inyx Usa Ltd.
  • Ivax Pharmaceuticals
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Par Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Servier Canada Inc.
  • UDL Laboratories
Dosage forms
FormRouteStrength
TabletOral
TabletOral1.25 mg/1
TabletOral2.5 mg/1
Tablet, film coatedOral1.25 mg/1
Tablet, film coatedOral2.5 mg/1
TabletOral2.5 mg
TabletOral1.25 mg
Prices
Unit descriptionCostUnit
Indapamide 2.5 mg tablet0.85USD tablet
Indapamide 1.25 mg tablet0.69USD tablet
Lozide 2.5 mg Tablet0.55USD tablet
Apo-Indapamide 2.5 mg Tablet0.31USD tablet
Mylan-Indapamide 2.5 mg Tablet0.31USD tablet
Novo-Indapamide 2.5 mg Tablet0.31USD tablet
Nu-Indapamide 2.5 mg Tablet0.31USD tablet
Pms-Indapamide 2.5 mg Tablet0.31USD tablet
Apo-Indapamide 1.25 mg Tablet0.2USD tablet
Mylan-Indapamide 1.25 mg Tablet0.2USD tablet
Pms-Indapamide 1.25 mg Tablet0.2USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)160-162U.S.Patent 3,565,911.
water solubility75 mg/LNot Available
logP2.2Not Available
pKa8.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0342 mg/mLALOGPS
logP2.52ALOGPS
logP2.64ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)8.85ChemAxon
pKa (Strongest Basic)0.097ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.5 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity103.31 m3·mol-1ChemAxon
Polarizability36.34 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8868
Caco-2 permeable-0.5529
P-glycoprotein substrateNon-substrate0.6859
P-glycoprotein inhibitor INon-inhibitor0.9158
P-glycoprotein inhibitor IINon-inhibitor0.9179
Renal organic cation transporterNon-inhibitor0.8575
CYP450 2C9 substrateNon-substrate0.5265
CYP450 2D6 substrateNon-substrate0.7924
CYP450 3A4 substrateNon-substrate0.519
CYP450 1A2 substrateInhibitor0.582
CYP450 2C9 inhibitorNon-inhibitor0.5775
CYP450 2D6 inhibitorNon-inhibitor0.8151
CYP450 2C19 inhibitorNon-inhibitor0.6572
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7471
Ames testNon AMES toxic0.6869
CarcinogenicityNon-carcinogens0.7674
BiodegradationNot ready biodegradable0.9862
Rat acute toxicity2.0823 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.986
hERG inhibition (predictor II)Non-inhibitor0.8804
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0009000000-ed04e0a5871badc8b166
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-1729000000-15aecb441ef4febfe526
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-2910000000-b72aeba8db62ebdf9c17
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004r-6900000000-f819fedd1ac654d46dd4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-9300000000-164a2972880c967d2195
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-9100000000-d18afa355f919614b652
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-01t9-9000000000-9d9e98925e9105738992
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03fr-9000000000-5e7568f4efd1730f47b9
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-9000000000-ecfffadaaa03b447eaf5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0904000000-530b78f6cae834e11768
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-235673a939e2e7d8c5e3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0159-0900000000-a843660d42ffb01666fe
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-cfee205b361c580e3631
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00lr-0900000000-a6d8ff4d769ea09e8073
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0901000000-a76c5fd366807c180552
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-574a71dcc7f0b3f74693
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1900000000-ab046a8849c404d9b308
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00l6-4900000000-93f1cc6465f329fd111e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-8900000000-0e98ece38603802699f7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-9600000000-c7e6e85faab95871c46d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-9300000000-d9a4af4e617331f29e98
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-9100000000-60cb951d344ed0385fc6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014u-9000000000-d07d645a1ccd383e7a1b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-1900000000-861314def0ccc019ac04
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-2900000000-10b16fdb4047a076cc32

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
4-halobenzoic acids and derivatives / Benzenesulfonyl compounds / Indoles and derivatives / Benzoyl derivatives / Chlorobenzenes / Organosulfonamides / Aryl chlorides / Aminosulfonyl compounds / Carboxylic acid hydrazides / Azacyclic compounds
show 6 more
Substituents
Benzenesulfonamide / Halobenzoic acid or derivatives / 4-halobenzoic acid or derivatives / Benzoic acid or derivatives / Benzenesulfonyl group / Indole or derivatives / Benzoyl / Chlorobenzene / Halobenzene / Aryl chloride
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, organochlorine compound, indoles (CHEBI:5893)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 Da
References
  1. Indapamide, International Union of Basic and Clinical Pharmacology Document [Link]
  2. Significant Drug–Drug Interactions with Antineoplastics [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sun H, Moore C, Dansette PM, Kumar S, Halpert JR, Yost GS: Dehydrogenation of the indoline-containing drug 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (indapamide) by CYP3A4: correlation with in silico predictions. Drug Metab Dispos. 2009 Mar;37(3):672-84. doi: 10.1124/dmd.108.022707. Epub 2008 Dec 12. [PubMed:19074530]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:31