Indapamide

Last updated
Indapamide
Indapamide.svg
Clinical data
Trade names Lozol, Natrilix
AHFS/Drugs.com Monograph
MedlinePlus a684062
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 binding 71–79%
Metabolism Liver
Elimination half-life 14–18 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.043.633 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H16ClN3O3S
Molar mass 365.83 g·mol−1
3D model (JSmol)
  • O=S(=O)(N)c1c(Cl)ccc(c1)C(=O)NN3c2ccccc2CC3C
  • 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) Yes check.svgY
  • Key:NDDAHWYSQHTHNT-UHFFFAOYSA-N Yes check.svgY
   (verify)

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]

Contents

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. [5] [9] [10] 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). [5] [10] [11] HYVET study showed that indapamide (sustained release), with or without perindopril as antihypertensive treatment in persons 80 years of age or older with sustained systolic blood pressure of 160 mmHg or higher, demonstrated significant reduction in all-cause mortality when treated to a target of 150/80 mmHg, but there was found to be no significant reduction in risk of death from cardiac causes. [5] Two systematic reviews identified that indapamide with or without perindopril significantly reduced all cause mortality in young-elderly patients with a history of stroke, cardiovascular disease and type 2 diabetes mellitus, when greater reductions in mean office blood pressure are achieved, significant cardiovascular benefit was only observed when trials including the >75 years old cohort was included. [5] [12] [13]

Contraindications

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

There is insufficient safety data to recommend indapamide use in pregnancy or breastfeeding.[ citation needed ]

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

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Thiazide</span> Class of chemical compounds

Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.

<span class="mw-page-title-main">Ramipril</span> ACE inhibitor medication

Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 years old to reduce the risk of having a heart attack, stroke or cardiovascular death in patients shown to be at high risk, such as some diabetics and patients with vascular disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Reserpine</span> Drug used to treat high blood pressure

Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available In 2012.

<span class="mw-page-title-main">Doxazosin</span> Group of stereoisomers

Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia and hypertension. For high blood pressure, it is a less preferred option. It is taken by mouth.

<span class="mw-page-title-main">Moxonidine</span> Antihypertensive medication

Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens and Moxon.

<span class="mw-page-title-main">Metolazone</span> Chemical compound

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and 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 diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

<span class="mw-page-title-main">Perindopril</span> High blood pressure medication

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.

<span class="mw-page-title-main">Perindopril/indapamide</span> Combination medication

Perindopril/indapamide is a combination medication which contains perindopril and indapamide both of which are used for the treatment of essential hypertension.

In medicine, systolic hypertension is defined as an elevated systolic blood pressure (SBP). If the systolic blood pressure is elevated (>140) with a normal (<90) diastolic blood pressure (DBP), it is called isolated systolic hypertension. Eighty percent of people with systolic hypertension are over the age of 65 years old. Isolated systolic hypertension is a specific type of widened pulse pressure.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

Hypertension is managed using lifestyle modification and antihypertensive medications. Hypertension is usually treated to achieve a blood pressure of below 140/90 mmHg to 160/100 mmHg. According to one 2003 review, reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21% and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.

An ACE inhibitor and thiazide combination is a drug combination used to treat hypertension. They are given by mouth. ACE inhibitors reduce the activity of angiotensin-converting enzyme (ACE) which produces angiotensin II, a hormone that constricts blood vessels. Thiazides are a class of diuretics that inhibit the thiazide receptor, thereby increasing urine production and reducing excess water and salt in the body. Several organizations recommend combination therapy for hypertension in cases of failure of a single drug to achieve target blood pressure, or even as a first line treatment for some patients.

<span class="mw-page-title-main">Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial</span>

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, also known as ALLHAT, was a randomized, double-blind, active-controlled study comparing at the same time, four different classes of antihypertensive drugs with the rate of coronary heart disease (CHD) events in ‘high-risk’ people with hypertension. Participants were initially randomised to chlorthalidone (diuretic) versus doxazosin, lisinopril (ACE-inhibitor), and amlodipine.

Refractory hypertension(RfHTN) is hypertension, a high blood pressure, that remains uncontrolled on maximal or near-maximal therapy, that includes the use of ≥5 antihypertensive agents of different classes. Agents used include a long-acting thiazide-like diuretic (such as chlorthalidone) and spironolactone. Refractory hypertension is typically associated with increased sympathetic nervous system activity. The phenotype of refractory hypertension was first proposed in a retrospective analysis of patients referred to the University of Alabama at Birmingham Hypertension Clinic whose blood pressure could not be controlled on any antihypertensive regimen.

References

  1. "Active substance(s): indapamide" (PDF). List of nationally authorised medicinal products. Human Medicines Evaluation Division, European Medicines Agency. 22 July 2021.[ permanent dead link ]
  2. Indapamide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  3. 1 2 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): 1033–1040. 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): 405–412. February 1992. doi:10.1136/bmj.304.6824.405. PMC   1995577 . PMID   1445513.
  5. 1 2 3 4 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". The New England Journal of Medicine. 358 (18): 1887–1898. doi: 10.1056/NEJMoa0801369 . PMID   18378519.
  6. Suchard MA, Schuemie MJ, Krumholz HM, You SC, Chen R, Pratt N, et al. (November 2019). "Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis". Lancet. 394 (10211): 1816–1826. doi:10.1016/s0140-6736(19)32317-7. 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. 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): 1032–1040. doi: 10.1038/hr.2009.139 . PMID   19798097.
  10. 1 2 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): 1033–1041. doi:10.1016/s0140-6736(01)06178-5. PMID   11589932. S2CID   10053225.
  11. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al. (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". Lancet. 370 (9590): 829–840. doi:10.1016/s0140-6736(07)61303-8. PMID   17765963. S2CID   21153924.
  12. 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): 1033–1040. doi: 10.1161/HYPERTENSIONAHA.114.05122 . PMID   25733241.
  13. Chalmers J, Mourad JJ, 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.