Skip to Content

Indapamide

Pronunciation

Pronunciation

(in DAP a mide)

Index Terms

  • Lozol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 1.25 mg, 2.5 mg

Pharmacologic Category

  • Antihypertensive
  • Diuretic, Thiazide-Related

Pharmacology

Diuretic effect is localized at the proximal segment of the distal tubule of the nephron; it does not appear to have significant effect on glomerular filtration rate nor renal blood flow; like other diuretics, it enhances sodium, chloride, and water excretion by interfering with the transport of sodium ions across the renal tubular epithelium

Absorption

Complete

Distribution

Vd: 25 L (Grebow, 1982)

Metabolism

Extensively hepatic

Excretion

Urine (~70%; 7% as unchanged drug within 48 hours); feces (23%)

Time to Peak

2 hours

Half-Life Elimination

Biphasic: 14 and 25 hours

Protein Binding

Plasma: 71% to 79%

Use: Labeled Indications

Heart failure: Treatment of edema in heart failure

Hypertension: Management of mild-to-moderate hypertension

Guideline recommendations:

Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:

• Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

• Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Chronic kidney disease (CKD) and hypertension: Regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general non-black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD), including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.

Coronary artery disease (CAD) and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with coronary artery disease (CAD) recommends the use of a thiazide (or thiazide-like diuretic) as part of a regimen in patients with hypertension and chronic stable angina. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).

Use: Unlabeled

Calcium nephrolithiasis: Prevention of recurrent calcium renal stones

Contraindications

Hypersensitivity to indapamide or any component of the formulation or sulfonamide-derived drugs; anuria

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.

Canadian labeling: Additional contraindications (not in U.S. labeling): Severe renal failure (CrCl <30 mL/minute); hepatic encephalopathy; severe hepatic impairment; hypokalemia; concomitant use with antiarrhythmic agents causing torsade de pointes; pregnancy; breast-feeding; hereditary problems of galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency

Dosing: Adult

Edema: Oral: Initial: 2.5 mg daily; if inadequate response after 1 week, may increase dose to 5 mg daily. Note: There is little therapeutic benefit to increasing the dose >5 mg daily; there is, however, an increased risk of electrolyte disturbances

Hypertension: Oral: Initial: 1.25 mg daily; if inadequate response, may increase dose once every 4 weeks to 2.5 mg daily and then to 5 mg daily if needed. Consider adding another antihypertensive and decreasing the dose if response is not adequate. Usual dosage range (ASH/ISH [Weber, 2014]): 1.25 to 2.5 mg daily. Note: Canadian labeling recommends a maximum dose of 2.5 mg daily.

Calcium nephrolithiasis (off-label use): Oral: 2.5 mg once daily (AUA [Pearle, 2014])

Dosing: Geriatric

U.S. labeling: Refer to adult dosing.

Canadian labeling: 1.25 mg daily

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution. Canadian labeling contraindicates use in severe impairment (CrCl <30 mL/minute).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution. Canadian labeling contraindicates use in severe hepatic impairment or hepatic encephalopathy.

Administration

May be administered without regard to meals (Caruso, 1983); however, administration with food or milk may decrease GI adverse effects. Administer early in day to avoid nocturia.

Dietary Considerations

May be taken without regard to meals (Caruso, 1983); however, administration with food or milk may to decrease GI adverse effects.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

ACE Inhibitors: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of ACE Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Monitor therapy

Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Salts: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy

CarBAMazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Cyclophosphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced. Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Consider therapy modification

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

OXcarbazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Test Interactions

May interfere with parathyroid function tests and may decrease serum iodine (protein bound) without signs of thyroid disturbance

Adverse Reactions

≥5%:

Central nervous system: Agitation, anxiety, dizziness, fatigue, headache, irritability, lethargy, malaise, nervousness (dose dependent), pain, tension, tiredness

Endocrine & metabolic: Hypokalemia (<3.5 mEq/L: 20% to 72%, dose dependent)

Neuromuscular & skeletal: Back pain, muscle cramps/spasm, paresthesia, weakness

Respiratory: Rhinitis

Miscellaneous: Infection

≥1% to <5%:

Cardiovascular: Arrhythmia, chest pain, flushing, orthostatic hypotension, palpitation, peripheral edema, PVC, vasculitis

Central nervous system: Depression, drowsiness, insomnia, lightheadedness, vertigo

Dermatologic: Hives, pruritus, rash

Endocrine & metabolic: Hyperglycemia, hyperuricemia, hypochloremia, hyponatremia, libido decreased

Gastrointestinal: Abdominal pain, anorexia, constipation, cramping, diarrhea, dyspepsia, gastric irritation, nausea, vomiting, weight loss, xerostomia

Genitourinary: Nocturia, polyuria

Neuromuscular & skeletal: Hypertonia

Ocular: Blurred vision, conjunctivitis

Renal: BUN increased, creatinine increased, glycosuria

Respiratory: Cough, pharyngitis, rhinorrhea, sinusitis

Miscellaneous: Flu-like syndrome

<1% (Limited to important or life-threatening): Agranulocytosis, anaphylactic reaction, aplastic anemia, bullous eruptions, erythema multiforme, fever, hepatitis, hypercalcemia, jaundice (cholestatic jaundice), leukopenia, liver function test abnormality, pancreatitis, photosensitivity, pneumonitis, purpura, Stevens-Johnson syndrome, thrombocytopenia, torsade de pointes

Warnings/Precautions

Concerns related to adverse effects:

• Electrolyte disturbances: Severe hyponatremia with hypokalemia has been reported at recommended doses (particularly in elderly women); risk may be dose dependent, therefore, use lowest dose possible. Hypochloremic alkalosis, hypomagnesemia, or hypercalcemia can also occur; monitor electrolytes periodically during therapy.

• Photosensitivity: Photosensitization may occur.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated.

• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Canadian labeling contraindicates use in severe hepatic impairment or hepatic encephalopathy.

• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; thiazide diuretics have been shown to increase cholesterol concentrations; however, indapamide (a thiazide-like diuretic) has not been shown to adversely affected lipids.

• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy. Canadian labeling contraindicates use in hypokalemia.

• Renal impairment: Use with caution in severe renal disease. Canadian labeling contraindicates use in severe renal failure (CrCl <30 mL/minute).

• Systemic lupus erythematosus (SLE): Can cause SLE exacerbation or activation.

Dosage forms specific issues:

• Lactose: Formulation may contain lactose; Canadian labeling recommends avoiding use in patients with hereditary conditions of galactose intolerance, glucose-galactose malabsorption, or lactase deficiency.

Monitoring Parameters

Blood pressure (both standing and sitting/supine); serum electrolytes, hepatic function, renal function, uric acid; assess weight, I & O reports daily to determine fluid loss

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Diuretics cross the placenta and are found in cord blood. Maternal use may cause may cause fetal or neonatal jaundice, thrombocytopenia, or other adverse events observed in adults. Use of diuretics during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor. Canadian labeling contraindicates use in pregnant women.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue, headache, loss of strength and energy, back pain, or rhinorrhea. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), angina, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide