Introduction
Indapamide is a thiazide-like diuretic and antihypertensive agent used primarily for the management of hypertension and edema associated with congestive heart failure. Unlike traditional thiazides, indapamide possesses both diuretic and direct vasodilatory properties, making it a versatile agent in cardiovascular management. It is classified as a sulfonamide derivative and is available in both standard and sustained-release formulations.
Mechanism of Action
Indapamide exerts its therapeutic effects through dual mechanisms: 1. Diuretic action: Inhibits sodium reabsorption in the cortical diluting segment of the distal convoluted tubule by competing for the chloride binding site on the Na+/Cl- cotransporter 2. Vasodilatory action: Reduces total peripheral resistance through calcium channel blockade in vascular smooth muscle cells and stimulation of prostaglandin synthesis
The drug demonstrates a dose-dependent response, with lower doses (1.25-2.5 mg daily) primarily producing vasodilation and higher doses (>2.5 mg) exhibiting more significant diuretic effects.
Indications
FDA-approved indications:- Hypertension (monotherapy or combination therapy)
- Edema associated with congestive heart failure
- Prevention of recurrent nephrolithiasis in hypercalciuric patients
- Adjuvant therapy in nephrogenic diabetes insipidus
Dosage and Administration
Hypertension:- Immediate-release: 1.25-5 mg once daily
- Sustained-release: 1.5 mg once daily
- 2.5-5 mg once daily (immediate-release formulation)
- Renal impairment: Use with caution; contraindicated in severe renal impairment (eGFR <30 mL/min)
- Hepatic impairment: Use with caution; contraindicated in severe hepatic impairment
- Elderly: Start with lower doses (1.25 mg daily)
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Well absorbed from GI tract (90% bioavailability); food does not significantly affect absorption Distribution: Volume of distribution: 25-60 L; Protein binding: 75-79% Metabolism: Hepatic metabolism via cytochrome P450 and glucuronidation Elimination: Half-life: 14-18 hours; Renal excretion (60-70%) and fecal excretion (20-23%) Onset of action: 1-2 hours; Peak effect: 2-3 hours; Duration: 24+ hoursContraindications
- Hypersensitivity to indapamide or sulfonamide-derived drugs
- Anuria
- Severe renal impairment (eGFR <30 mL/min)
- Severe hepatic impairment or hepatic encephalopathy
- Pre-existing significant hypokalemia or hyponatremia
- Addison's disease
Warnings and Precautions
Black Box Warning: None Important precautions:- Electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia)
- Metabolic alkalosis
- Hyperuricemia and gout exacerbation
- Impaired glucose tolerance
- Photosensitivity reactions
- Systemic lupus erythematosus exacerbation
- Orthostatic hypotension
- Renal function deterioration
Drug Interactions
Major interactions:- Lithium: Reduced renal clearance, increased lithium toxicity risk
- NSAIDs: Reduced antihypertensive effect and increased renal toxicity
- Digoxin: Hypokalemia may potentiate digoxin toxicity
- Other antihypertensives: Additive hypotensive effects
- Corticosteroids: Enhanced potassium wasting
- Cholestyramine: Reduced indapamide absorption
- QT-prolonging agents: Increased risk of torsades de pointes
Adverse Effects
Common (≥1%):- Headache (6-9%)
- Dizziness (5-8%)
- Fatigue (3-5%)
- Muscle cramps/spasms (2-4%)
- Nausea (2-3%)
- Orthostatic hypotension (2-3%)
- Severe electrolyte disturbances
- Acute interstitial nephritis
- Pancreatitis
- Hepatic dysfunction
- Blood dyscrasias (thrombocytopenia, leukopenia, agranulocytosis)
- Stevens-Johnson syndrome
- Allergic reactions including anaphylaxis
Monitoring Parameters
Baseline:- Complete blood count
- Comprehensive metabolic panel (including electrolytes, renal function)
- Uric acid level
- Blood pressure measurement
- ECG (if cardiac history present)
- Blood pressure at each visit
- Serum electrolytes (potassium, sodium) within 1-2 weeks of initiation and periodically thereafter
- Renal function every 3-6 months
- Serum glucose (especially in diabetic patients)
- Body weight for edema monitoring
- Clinical signs of fluid/electrolyte imbalance
Patient Education
- Take in morning to avoid nocturnal diuresis
- Report signs of electrolyte imbalance: muscle weakness, cramps, fatigue, dizziness
- Monitor weight regularly if prescribed for edema
- Maintain adequate fluid intake unless contraindicated
- Avoid excessive alcohol consumption
- Use sun protection due to photosensitivity risk
- Rise slowly from sitting/lying position to prevent dizziness
- Do not discontinue abruptly without medical supervision
- Inform all healthcare providers about indapamide use
- Report any unusual bleeding or bruising
References
1. FDA Prescribing Information: Indapamide Tablets 2. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003;289:2560-72 3. Ernst ME, et al. Diuretics: A review and update. J Cardiovasc Pharmacol Ther 2020;25(6):514-525 4. Sica DA, et al. Diuretic-related side effects: development and treatment. J Clin Hypertens 2019;21(1):92-97 5. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int 2021;99(3S):S1-S87 6. Williams B, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39(33):3021-3104 7. UpToDate: Indapamide drug information 8. Micromedex® Healthcare Series: Indapamide monograph