Class: Thiazide-like Diuretics
VA Class: CV701
Chemical Name: 3-(Aminosulfonyl)-4-chloro-N-(2,3-dihydro-2-methyl-1H-indol-1-yl)benzamide
Molecular Formula: C16H16ClN3O3S
CAS Number: 26807-65-8
Medically reviewed by Drugs.com. Last updated on Jan 14, 2019.
An indoline diuretic and antihypertensive agent; pharmacologically similar to thiazide diuretics.83
Uses for Indapamide
Thiazide-type diuretics are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and calcium-channel blockers.502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 504 1200
Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201
A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)
Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.
Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).
SBP (mm Hg)
DBP (mm Hg)
Hypertension, Stage 1
Hypertension, Stage 2
The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229
The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BPs to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210
Previous hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with501 504 536 those recommended by the 2017 ACC/AHA hypertension guideline.1200
Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229
Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229
For decisions regarding when to initiate drug therapy (BP threshold), the current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.1200
ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200
For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200
Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years of age are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200
In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200
Black hypertensive patients generally tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).82 200 501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200
Thiazide-like diuretics may be preferred in hypertensive patients with osteoporosis. Secondary beneficial effect in hypertensive geriatric patients of reducing the risk of osteoporosis secondary to effect on calcium homeostasis and bone mineralization.
Edema in Heart Failure
Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.524 700 713
Diuretics produce rapid symptomatic benefits, relieving pulmonary and peripheral edema more rapidly (within hours or days) than cardiac glycosides, ACE inhibitors, or β-blockers (in weeks or months).70
Loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are diuretics of choice for most patients with heart failure.524
Edema in Pregnancy
Diuretics should not be used for routine therapy in pregnant women with mild edema who are otherwise healthy.a
Use of thiazide-like diuretics may be appropriate in the management of edema of pathologic origin during pregnancy when clearly needed; routine use of diuretics in otherwise healthy pregnant women is irrational.21 30
Dependent edema secondary to restriction of venous return by the expanded uterus should be managed by elevating the lower extremities and/or by wearing support hose; use of diuretics in these pregnant women is inappropriate.21 30
In rare cases when the hypervolemia associated with normal pregnancy results in edema that produces extreme discomfort, a short course of diuretic therapy may provide relief and may be considered when other methods (e.g., decreased sodium intake, increased recumbency) are ineffective.21 30 44
No substantial difference in clinical effects or toxicity of comparable thiazide or thiazide-like diuretics, except metolazone may be more effective in edema with renal impairment.a
Indapamide Dosage and Administration
Monitoring and BP Treatment Goals
Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200
Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.1200 (See Fluid and Electrolyte Imbalance under Cautions.)
If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker).1200 1216 Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.1200 1216 1220
Individualize dosage according to individual requirements and response.600
For the management of fluid retention (e.g., edema) associated with heart failure, experts state that diuretics should be administered at a dosage sufficient to achieve optimal volume status and relieve congestion without inducing an excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both.524
Manufacturer recommends initial dosage of 1.25 mg once daily in the morning; if response is inadequate, dosage may be increased at 4-week intervals to 2.5 mg daily and subsequently to 5 mg daily.83
Some experts state that usual dosage range is 1.25–2.5 mg once daily.1200
Dosages >5 mg daily do not appear to result in further improvement in BP and increase the risk of hypokalemia.83 (See Hypokalemia under Cautions.)
If concomitant therapy with other antihypertensive agents is required, the usual dose of the other agent may need to be reduced initially by up to 50%; subsequent dosage adjustments should be based on BP response.44 83 Dosage reduction of both drugs may be required.39
Edema in Heart Failure
Initially, 2.5 mg once daily in the morning.83
Dosages >5 mg daily do not appear to result in further improvement in heart failure or BP and are associated with increased risk of hypokalemia;24 29 39 83 clinical experience with such dosages is limited.24 29 39 83
No specific dosage recommendations.83 (See Hepatic Impairment under Cautions.)
No specific dosage recommendations.83 (See Geriatric Use under Cautions.)
Cautions for Indapamide
Severe hyponatremia (serum sodium concentration <120 mEq/L), accompanied by hypokalemia, occurs rarely.51 52 53 54 55 56 57 58 59 60 61 Do not administer sodium chloride unless the hyponatremia is life threatening or actual sodium depletion is documented.21 If sodium chloride is administered, initially only correct to a state of mild hyponatremia; avoid early overcorrection to normonatremia or hypernatremia (risk of central pontine myelinolysis).52 55 60 62
Possible dilutional hyponatremia; occurs most commonly in patients with edema.21 51 54 Usually asymptomatic and managed by fluid intake restriction (e.g., 500 mL/day)21 and withdrawal of the diuretic.51 54
Hypokalemia occurs commonly.9 21 24 28 47 Increased risk of hypokalemia, especially with brisk diuresis; large dosages (i.e., ≥5 mg daily);21 24 29 39 40 83 inadequate oral electrolyte intake; in presence of severe cirrhosis, hyperaldosteronism, or potassium-losing renal diseases; or during concomitant use of corticosteroids or ACTH.21 24 83
Generally, do not use with lithium salts.21 (See Specific Drugs under Interactions.)
Rash (e.g., erythematous, maculopapular, morbilliform), urticaria, pruritus, and vasculitis reported.21 63 In some cases, rash was accompanied by fever and/or dysuria.63 Rash generally resolves within 2 weeks after drug discontinuance, usually without specific therapy.63 64 May be treated with antihistamines.63
Fluid and Electrolyte Imbalance
Periodic determinations of serum electrolyte concentrations (particularly potassium, sodium, chloride, and bicarbonate) should be performed and are especially important in patients at increased risk from hypokalemia (e.g., geriatric patients, those with cardiac arrhythmias, receiving concomitant cardiac glycosides, and/or with a history of ventricular arrhythmias),21 24 39 1200 and those with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of other electrolyte imbalance (e.g., heart failure, renal disease, cirrhosis, restricted sodium intake, advanced age).21 83 1200
Observe carefully for manifestations of fluid and electrolyte depletion (e.g., dryness of mouth, thirst, weakness, fatigue, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, GI disturbance).21 83 1200 Measures to maintain normal serum concentrations should be instituted if necessary.21 83
Risk of hyperuricemia, especially in patients with a history of gout, family predisposition to gout, or chronic renal failure.4 10 12 17 25 28 29 39 47 Usually asymptomatic and rarely leads to clinical gout.19 21 24 28 29 39
Risk of increased blood glucose, hyperglycemia, glycosuria, and impaired glucose tolerance;15 21 24 28 precipitation of diabetes mellitus rarely reported in patients with a history of impaired glucose tolerance (latent diabetes).21
Monitor blood glucose concentrations periodically, especially in patients with known or suspected (e.g., marginally impaired glucose tolerance) diabetes mellitus.21
May decrease calcium urinary excretion; slight intermittent serum calcium increases reported;83 clinically important changes in serum total or ionic calcium concentrations have not been reported.20 21 24
Antihypertensive effect may be enhanced after sympathectomy.21
Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540
Safety and efficacy not established.83
Increased risk of hypochloremic alkalosis associated with hypokalemia.21
Increased risk of hypochloremic alkalosis associated with hypokalemia.21
Evaluate renal function (e.g., BUN, Scr) periodically.21
Common Adverse Effects
Hypokalemia,9 21 24 28 47 headache,3 21 24 28 dizziness,3 21 24 28 29 fatigue,3 21 24 weakness,21 29 lethargy,21 tiredness,21 malaise,21 muscle cramps or spasm,3 21 24 29 numbness of the extremities,21 nervousness,21 24 tension, anxiety, irritability, agitation.21 83
Interactions for Indapamide
If concomitant therapy with other antihypertensive agents is required, dose of the other agent may need to be reduced initially by up to 50%; subsequent dosage adjustments should be based on BP response;44 83 dosage reduction of both drugs may be required39
Monitor for possible postural hypotension21
Possible electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) may predispose to digitalis toxicity; possibly fatal cardiac arrhythmias21
Monitor electrolytes; correct hypokalemia21
Diuretics, potassium-sparing (e.g., amiloride, triamterene)
Concomitant therapy not fully evaluated40
Safety and efficacy of concurrent use for the prevention of hypokalemia have not been fully determined40
Monitor blood glucose concentrations periodically, especially in patients with known or suspected (e.g., marginally impaired glucose tolerance) diabetes mellitus21
Concomitant use generally contraindicated21
Potassium-depleting drugs (e.g., corticosteroids, corticotropin, amphotericin B)
Additive hypokalemic effects21
Monitor electrolytes; correct hypokalemia83
Vasopressors (e.g., norepinephrine, phenylephrine)
Unlikely to be clinically important21
Plasma Protein Binding
Not removed from circulation by hemodialysis.4
Tight, light-resistant containers at 20–25°C; avoid excessive heat.600
Precise mechanism of hypotensive action has not been determined, but postulated that diuretics lower BP mainly by reducing plasma and extracellular fluid volume41 44 and by decreasing peripheral vascular resistance possibly secondary to sodium depletion43 and/or vascular autoregulatory feedback mechanisms;41 however, part of the hypotensive effect of indapamide may be caused by direct arteriolar dilation.5 6 21 24 25 27 39
Advice to Patients
Importance of informing patients of the signs and symptoms of electrolyte imbalance and instructing them to contact their clinician if dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, oliguria, hypotension, tachycardia, GI disturbance, or muscle pains or cramps occur.21
Importance of informing patients with diabetes mellitus that blood glucose and urine glucose concentrations may increase.83
Advise hypertensive patients of importance of continuing lifestyle/behavioral modifications that include weight reduction (for those who are overweight or obese), dietary changes to include foods that are rich in potassium and calcium and moderately restricted in sodium (adoption of the Dietary Approaches to Stop Hypertension [DASH] eating plan), increased physical activity, smoking cessation, and moderation of alcohol intake.1200
Advise that lifestyle/behavioral modifications reduce BP, enhance antihypertensive drug efficacy, and decrease cardiovascular risk and remain an indispensable part of the management of hypertension.1200
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.83
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.83
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS DI Essentials™. © Copyright 2019, Selected Revisions January 14, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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