Indapamide

Indapamide is a thiazide-like diuretic[2] drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril (an ACE inhibitor antihypertensive) are available. The thiazide-like diuretics (indapamide and chlorthalidone) reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events.[3] Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke.[3][4][5] Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.[3][6]

Indapamide
Clinical data
Trade namesLozol, Natrilix
AHFS/Drugs.comMonograph
MedlinePlusa684062
Pregnancy
category
  • AU: C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • EU: Rx-only [1]
Pharmacokinetic data
Protein binding71–79%
MetabolismLiver
Elimination half-life14–18 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.633
Chemical and physical data
FormulaC16H16ClN3O3S
Molar mass365.83 g·mol−1
3D model (JSmol)
SMILES
  • O=S(=O)(N)c1c(Cl)ccc(c1)C(=O)NN3c2ccccc2CC3C
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) Y
  • Key:NDDAHWYSQHTHNT-UHFFFAOYSA-N Y
  (verify)

It was patented in 1968 and approved for medical use in 1977.[7] It is on the World Health Organization's List of Essential Medicines.[8]

Medical uses

Its indications include hypertension and edema due to congestive heart failure. Indapamide has been shown to reduce stroke rates in people with high blood pressure.[9][10][11] Studies have shown that the blood pressure lowering effects of indapamide in combination with perindopril reduce the rate of stroke in high risk patients (those with a history of high blood pressure, stroke or type two diabetes).[9][11][12] The HYVET study was one of the first landmark trials to demonstrate a significant reduction in all cause mortality in octogenarians, with or without the addition of perindopril.[9] Two systematic reviews also identified reductions in all cause mortality with thiazide-like diuretics, including indapamide, in octogenarians, as well as in young-elderly patients.[9][13][14]

Contraindications

Indapamide is contraindicated in known hypersensitivity to sulfonamides, severe kidney failure, hepatic encephalopathy or severe liver failure, and a low blood potassium level.

There is insufficient safety data to recommend indapamide use in pregnancy or breastfeeding.

Adverse effects

Commonly reported adverse events are low potassium levels, fatigue, orthostatic hypotension (an exaggerated decrease in blood pressure upon standing, often associated with syncope), and allergic manifestations.

Monitoring the serum levels of potassium and uric acid is recommended, especially in subjects with a predisposition to low levels of potassium in the blood and gout.

Interactions

Caution is advised in the combination of indapamide with lithium and drugs causing prolonged QT interval (on EKG) or wave-burst arrhythmia (i.e.: astemizole, bepridil, IV erythromycin, halofantrine, pentamidine, sultopride, terfenadine, and vincamine).

Overdose

Symptoms of over dosage would be those associated with a diuretic effect (i.e. electrolyte disturbances), low blood pressure, and muscular weakness. Treatment should be symptomatic, directed at correcting electrolyte abnormalities.

See also

References
  1. https://www.ema.europa.eu/documents/psusa/indapamide-list-nationally-authorised-medicinal-products-psusa-00001731-202011_en.pdf
  2. Indapamide at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. Olde Engberink RH, Frenkel WJ, van den Bogaard B, Brewster LM, Vogt L, van den Born BJ (May 2015). "Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis". Hypertension. 65 (5): 1033–40. doi:10.1161/HYPERTENSIONAHA.114.05122. PMID 25733241.
  4. "Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party". BMJ. 304 (6824): 405–12. February 1992. doi:10.1136/bmj.304.6824.405. PMC 1995577. PMID 1445513.
  5. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. (May 2008). "Treatment of hypertension in patients 80 years of age or older" (PDF). The New England Journal of Medicine. 358 (18): 1887–98. doi:10.1056/NEJMoa0801369. PMID 18378519.
  6. Suchard, Marc A; Schuemie, Martijn J; Krumholz, Harlan M; You, Seng Chan; Chen, RuiJun; Pratt, Nicole; Reich, Christian G; Duke, Jon; Madigan, David; Hripcsak, George; Ryan, Patrick B (November 2019). "Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis". The Lancet. 394 (10211): 1816–1826. doi:10.1016/s0140-6736(19)32317-7. ISSN 0140-6736. PMC 6924620. PMID 31668726.
  7. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 457. ISBN 9783527607495.
  8. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  9. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. (May 2008). "Treatment of hypertension in patients 80 years of age or older" (PDF). The New England Journal of Medicine. 358 (18): 1887–98. doi:10.1056/NEJMoa0801369. PMID 18378519.
  10. Liu L, Wang Z, Gong L, Zhang Y, Thijs L, Staessen JA, Wang J (November 2009). "Blood pressure reduction for the secondary prevention of stroke: a Chinese trial and a systematic review of the literature". Hypertension Research. 32 (11): 1032–40. doi:10.1038/hr.2009.139. PMID 19798097.
  11. PROGRESS Collaborative Group (September 2001). "Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack". Lancet. 358 (9287): 1033–41. doi:10.1016/s0140-6736(01)06178-5. PMID 11589932. S2CID 10053225.
  12. Patel, Anushka (September 2007). "Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial". The Lancet. 370 (9590): 829–840. doi:10.1016/s0140-6736(07)61303-8. ISSN 0140-6736. PMID 17765963. S2CID 21153924.
  13. Olde Engberink Rik H.G.; Frenkel Wijnanda J.; van den Bogaard Bas; Brewster Lizzy M.; Vogt Liffert; van den Born Bert-Jan H. (2015-05-01). "Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and Mortality". Hypertension. 65 (5): 1033–1040. doi:10.1161/HYPERTENSIONAHA.114.05122. PMID 25733241.
  14. Chalmers, J.; Mourad, J. J.; De Champvallins, M.; Mancia, G. (July 2019). "Benefit of Indapamide-Based Treatment on Mortality". Journal of Hypertension. 37: e57. doi:10.1097/01.hjh.0000570928.33807.a8. ISSN 0263-6352.
  • "Indapamide". Drug Information Portal. U.S. National Library of Medicine.
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