Indicontin

Approved Indications

• Hypertension (Primary / Essential):
• Used alone or in combination with other antihypertensive agents to lower blood pressure, thereby reducing the risk of stroke, myocardial infarction, and cardiovascular mortality.
• Edema associated with heart failure:
• Management of mild to moderate fluid retention in patients with congestive heart failure (CHF).

Important Clinically Accepted Off-Label Uses

• Nephrogenic diabetes insipidus (adjunct): Used when thiazide or thiazide-like diuretics are indicated to reduce polyuria.
• Renal calcium stone prophylaxis: In certain hypercalciuric patients to reduce urinary calcium excretion.
• Meniere’s disease / idiopathic endolymphatic hydrops: For symptomatic relief of vertigo and fluid retention.

Route: Oral only.

Adults

• Hypertension:
• Immediate-release: 1.25–2.5 mg once daily in the morning.
• Sustained-release (SR): 1.5 mg once daily in the morning.
• May be combined with other antihypertensive agents if needed.
• Edema (CHF):
• Immediate-release: 2.5 mg once daily in the morning. Dose adjustments made according to response.

Pediatric Use

• Safety and efficacy not established; not routinely recommended.

Elderly

• Same dosing as adults, but start at the lower end of the range; monitor electrolytes closely.

Renal Impairment

• Contraindicated in severe renal impairment (CrCl < 30 mL/min).
• In mild to moderate impairment, use with caution and monitor renal function and electrolytes.

Hepatic Impairment

• Contraindicated in severe hepatic impairment, especially with hepatic encephalopathy risk.
• Mild impairment: Use with caution.

Administration Notes

• Take in the morning to avoid nocturia.
• May be taken with or without food.
• Consistent daily timing optimizes BP control.

Indapamide is a thiazide-like diuretic that inhibits sodium and chloride reabsorption in the cortical diluting segment of the distal convoluted tubule by blocking the Na⁺/Cl⁻ symporter. This promotes excretion of sodium, chloride, and water, with secondary loss of potassium and magnesium, and reduced urinary calcium excretion. In addition to its diuretic effect, indapamide has direct vasodilatory action on vascular smooth muscle by reducing calcium influx, which lowers peripheral vascular resistance, contributing to its antihypertensive effect even at doses below the diuretic threshold.

• Absorption: Rapid and nearly complete oral absorption; bioavailability ~93%.
• Onset: Antihypertensive effect within 24 hours; diuretic effect within 1–2 hours.
• Peak plasma concentration: ~1–2 hours (IR), ~12 hours (SR).
• Protein binding: ~71–79%.
• Distribution: Widely distributed; crosses the placenta and small amounts into breast milk.
• Metabolism: Extensively metabolized in the liver via non-CYP oxidative pathways.
• Half-life: 14–25 hours (IR); 16–25 hours (SR).
• Elimination: Primarily renal (urine) as metabolites; some fecal excretion.
• Steady state: Achieved within 7 days.

• Pregnancy:
• FDA Category: Not formally assigned; generally avoided unless benefit outweighs risk.
• Thiazide-like diuretics can reduce plasma volume, placental perfusion, and may cause fetal electrolyte imbalance, jaundice, or thrombocytopenia.
• Lactation:
• Excreted in small amounts in human milk. May cause electrolyte disturbances in the infant; breastfeeding not recommended during therapy.
• Recommendation: Avoid during pregnancy and lactation unless absolutely necessary.

• Primary class: Thiazide-like diuretic.
• Subclass: Non-thiazide sulfonamide diuretic with additional vasodilatory properties.

• Hypersensitivity to indapamide, sulfonamide-derived drugs, or any excipients.
• Severe renal impairment (CrCl < 30 mL/min).
• Severe hepatic impairment or hepatic encephalopathy.
• Hypokalemia.
• Refractory hyponatremia.
• Anuria.

• Electrolyte disturbances: Risk of hypokalemia, hyponatremia, hypomagnesemia, and hypercalcemia; monitor regularly.
• Volume depletion: May cause symptomatic hypotension, especially in elderly or volume-depleted patients.
• Hepatic encephalopathy: Risk increased in severe liver disease.
• Hyperuricemia: Can precipitate gout attacks.
• Hyperglycemia: May impair glucose tolerance in diabetics.
• Renal function deterioration: Monitor closely, especially in elderly or CKD patients.
• Photosensitivity reactions: Rare; avoid excessive sun exposure.
• Arrhythmia risk: Potentiated in hypokalemia, especially with digitalis therapy.

Common (≥1%)

• Metabolic: Hypokalemia, hyponatremia, hyperuricemia.
• Cardiovascular: Hypotension, orthostatic dizziness.
• Gastrointestinal: Nausea, constipation, abdominal pain.
• Neurological: Headache, fatigue.

Uncommon/Rare

• Hypomagnesemia, hypercalcemia.
• Rash, pruritus, photosensitivity.
• Muscle cramps, weakness.
• Arrhythmias due to electrolyte imbalance.
• Pancreatitis (rare).
• Blood dyscrasias (very rare).

Timing: Electrolyte changes often occur within first 2 weeks; metabolic side effects are dose-dependent.

• Lithium: Reduced clearance → risk of lithium toxicity.
• Digitalis glycosides: Hypokalemia increases arrhythmia risk.
• Potassium-lowering drugs (e.g., corticosteroids, amphotericin B): Additive hypokalemia.
• Antihypertensives: Additive BP lowering; may require dose adjustment.
• NSAIDs: May reduce diuretic and antihypertensive effect; risk of renal impairment.
• QT-prolonging drugs: Hypokalemia increases torsades de pointes risk.
• Alcohol: Enhanced orthostatic hypotension.

• Latest hypertension guidelines (e.g., 2023 ESH, 2024 AHA/ACC):
• Indapamide recommended as an effective first-line option for hypertension, particularly in elderly and isolated systolic hypertension.
• Lower doses preferred to minimize metabolic side effects.
• No recent FDA/EMA safety restrictions; ongoing monitoring advised for electrolyte changes.

• Store below 30°C in a dry place.
• Protect from light and moisture.
• Keep in original packaging until administration.
• Keep out of reach of children.
• Do not use after expiry date.