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
Uses for Indapamide
The JNC 7 classifies indapamide as a thiazide-like drug with regard to management of hypertension; the drug’s efficacy in hypertensive patients is similar to that of the thiazide diuretics.1 14 18 21 24 48 66 84
Thiazide-like drugs have well-established benefits, can be useful in achieving goal BP alone or combined with other antihypertensive drugs, enhance the antihypertensive efficacy of multidrug regimens, and are more affordable than other agents.84 a b
JNC 7 recommends that thiazide-like drugs be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).b
Most hypertension outcome studies have involved thiazide-like drugs, which generally have been unsurpassed in preventing cardiovascular complications of hypertension and are relatively inexpensive and well tolerated.b
The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage.b The higher the baseline BP, the more likely the development of MI, heart failure, stroke, and renal disease.b
Effective antihypertensive therapy reduces the risk of stroke by about 34–40%, MI by about 20–25%, and heart failure by more than 50%.b
Antihypertensive drug therapy is recommended for all patients with SBP/DBP ≥140/90 mm Hg who fail to respond to life-style/behavioral modifications.b
Initial antihypertensive therapy with drugs generally is recommended for anyone with diabetes mellitus, chronic renal impairment, or heart failure having SBP ≥130 mm Hg or DBP ≥80 mm Hg.b
Black hypertensive patients generally tend to respond better to monotherapy with diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.b
Diuretics largely eliminate the diminished response in blacks to ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.b
Thiazide-like drugs are preferred in hypertensive patients with osteoporosis.b Secondary beneficial effect in hypertensive geriatric patients of reducing the risk of osteoporosis secondary to effect on calcium homeostasis and bone mineralization.b
Although hypertension during pregnancy responds well to thiazide-like drugs, and the drugs had been used widely in the past for preeclampsia and eclampsia,a d such use no longer is recommended and other antihypertensives (e.g., methyldopa, hydralazine, labetolol) currently are preferred.b
Edema in CHF
Used in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-adrenergic blocking agent, with or without a cardiac glycoside.70
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 CHF.70
Edema in Pregnancy
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
BP Monitoring and Treatment Goals
Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.a
Avoid large or abrupt reductions in BP.a
Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients [stage 2 hypertension, comorbid conditions]) if BP control is inadequate at a given dosage; it may take months to control hypertension adequately while avoiding adverse effects of therapy.a
The goal is to achieve and maintain a lifelong SBP <140 mm Hg and a DBP <90 mm Hg if tolerated.a
The goal in hypertensive patients with diabetes mellitus or renal impairment is to achieve and maintain a SBP <130 mm Hg and a DBP <80 mm Hg.a
Initially, 1.25 mg once daily in the morning.83
If response is inadequate, dosage may be increased at 4-week intervals to 2.5 mg daily and subsequently to 5 mg daily.83
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 CHF
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 such dosages have been employed only in a limited number of clinical studies.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.1 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
Risk of electrolyte disturbances (e.g., hyponatremia, hypokalemia, hypochloremic alkalosis, hypomagnesemia).21 (See Hyponatremia and also Hypokalemia under Cautions.)
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),1 21 24 39 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
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 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.1 4 10 12 17 25 28 29 39 47 Usually asymptomatic and rarely leads to clinical gout.1 19 21 24 28 29 39
Generally avoid or use with caution in hypertensive patients with a history of gout or elevated uric acid concentrations.b
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
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 containers at 20–25°C; avoid excessive heat.83
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
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.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Indapamide 1.25MG Tablets (MYLAN): 90/$15.99 or 180/$19.97
Indapamide 2.5MG Tablets (MYLAN): 30/$13.99 or 90/$19.97
AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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- Other brands: Lozol