Is oindapamide (thiazide-like diuretic) similar to traditional thiazide diuretics in terms of pharmacological properties and effects?

Is Indapamide a Thiazide-Like Diuretic?

Yes, indapamide is classified as a thiazide-like (or non-thiazide sulfonamide) diuretic, not a traditional thiazide diuretic, despite sharing similar clinical effects and applications in hypertension management.

Chemical and Pharmacological Classification

Indapamide differs fundamentally from traditional thiazides in its molecular structure:

• Indapamide lacks the thiazide ring system and contains only one sulfonamide group, whereas traditional thiazides possess the characteristic benzothiadiazine ring structure 1
• The European Society of Cardiology explicitly states that "indapamide is a non-thiazide sulfonamide" 2
• Its molecular structure includes both a polar sulfamoyl chlorobenzamide moiety and a lipid-soluble methylindoline moiety, making it chemically distinct from hydrochlorothiazide and other traditional thiazides 1

Clinical Equivalence Despite Chemical Differences

Despite the chemical distinction, indapamide functions similarly to thiazide diuretics in clinical practice:

• Major guidelines group indapamide with chlorthalidone as "thiazide-like" diuretics that are preferred over traditional thiazides like hydrochlorothiazide 2
• The American College of Cardiology/American Heart Association identifies chlorthalidone and indapamide as preferred diuretics due to their longer duration of action compared to traditional thiazide diuretics 3
• Both chlorthalidone and indapamide have substantially more cardiovascular disease risk reduction data than hydrochlorothiazide, supporting their preferential use 3, 4

Mechanism of Action and Unique Properties

Indapamide exhibits pharmacological properties that extend beyond simple diuresis:

• While it exerts antihypertensive effects primarily through natriuretic diuretic action, indapamide also demonstrates direct vascular effects and has been categorized as having calcium channel blocking properties 1, 5
• It provides vasorelaxant activities that may contribute to its long-term antihypertensive efficacy beyond volume depletion 5
• The drug has a long terminal half-life in whole blood of approximately 14 hours, permitting once-daily administration 6

Guideline Recommendations and Clinical Use

International guidelines consistently recommend thiazide-like diuretics over traditional thiazides:

• European cardiovascular prevention guidelines state that thiazide and thiazide-like diuretics (chlorthalidone and indapamide) can adequately lower blood pressure and significantly reduce cardiovascular morbidity and mortality 2
• British guidelines recommend offering "a thiazide-like diuretic, such as chlorthalidone or indapamide, in preference to a conventional thiazide diuretic" when initiating or changing diuretic therapy 2
• Studies demonstrate that chlorthalidone and indapamide reduce cardiovascular morbidity and mortality, whereas there is no study indicating that hydrochlorothiazide has beneficial effects on cardiovascular outcomes such as myocardial infarction or stroke 7

Dosing in Heart Failure and Hypertension

Standard dosing reflects indapamide's classification as distinct from traditional thiazides:

• In heart failure management, the ESC lists indapamide separately from thiazides with an initial dose of 2.5 mg and usual daily dose of 2.5-5 mg 2
• For hypertension, guidelines recommend indapamide 1.5 mg modified-release once daily or 2.5 mg once daily 2
• The FDA label indicates that daily doses between 1.25 mg and 10 mg produce dose-related antihypertensive effects, with 2.5 mg and 5 mg being the most commonly used doses 6

Metabolic and Safety Profile

Indapamide demonstrates a favorable metabolic profile compared to traditional thiazides:

• Indapamide has no adverse impact on glucose and lipid metabolism, distinguishing it from hydrochlorothiazide which has dyslipidemic and diabetogenic effects 5, 2
• In elderly hypertensive patients, indapamide failed to alter significantly serum ionic composition, whereas hydrochlorothiazide was associated with both hyponatremia and hypokalemia 8
• At therapeutic doses, indapamide causes less hypokalemia and hyperuricemia compared to equivalent doses of hydrochlorothiazide 8

Common Pitfalls to Avoid

• Do not assume indapamide and hydrochlorothiazide are interchangeable simply because both are used for hypertension—they have different chemical structures, durations of action, and cardiovascular outcome data 9, 7
• Do not discontinue thiazide-like diuretics when eGFR decreases to <30 mL/min/1.73 m² without considering that they may still provide benefit, particularly when used synergistically with loop diuretics 2
• Do not overlook the cardiovascular outcome benefits that distinguish thiazide-like diuretics (indapamide, chlorthalidone) from traditional thiazides—this is the primary reason for guideline preference 9, 7