NATRILIX SR​ ​TABLETS

Indications

• Essential hypertension
• Management of fluid retention

Dosage

Adults: For adult patients, the usual dose is 2.5 mg once daily, which should be taken in the morning. In cases where a modified-release formulation is used, the dose may

Mechanism of action

Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter. This inhibition leads to reduced sodium reabsorption, causing sodium and water to remain in the nephron lumen for urinary excretion. Consequently, this results in decreased plasma volume, venous return, and cardiac output, ultimately lowering blood pressure. Additionally, indapamide may decrease responsiveness to pressor agents and reduce peripheral resistance, although these mechanisms require further investigation.

Pharmacodynamics

Indapamide is classified as a sulfonamide diuretic and is recognized for its efficacy in managing hypertension and preventing target organ damage. It induces water and electrolyte loss, with higher doses correlating with increased diuresis. Indapamide can cause significant electrolyte disturbances, such as hypokalemia, which may lead to QTc prolongation. It also influences plasma levels of renin and aldosterone while decreasing calcium excretion. Importantly, studies indicate that indapamide does not significantly alter glucose tolerance in hypertensive patients, although long-term metabolic effects remain to be fully elucidated.

Pharmacokinetics

Indapamide is absorbed orally and has a bioavailability that can be affected by food. It is extensively metabolized in the liver, with metabolites primarily excreted in urine. The drug has a half-life of approximately 14 to 18 hours, allowing for once-daily dosing. Renal function can influence the pharmacokinetics of indapamide, necessitating caution in patients with renal impairment due to the risk of hyperkalaemia.

Contra-indications

• Hypersensitivity to sulfonamides
• Severe renal impairment

Adverse effects

• Hypokalemia
• Dehydration
• Electrolyte disturbances
• Hypotension
• Dizziness
• Dry mouth
• Fatigue
• Restlessness
• Angina pectoris
• Arrhythmias
• Arthralgia
• Asthenia
• Chest pain
• Confusion
• Severe cutaneous adverse reactions
• Vision disorders
• Rhabdomyolysis
• QT interval prolongation

Interactions

• Potassium-sparing diuretics
• Thiazide diuretics
• Pressor agents
• Other antihypertensives

Precautions

• Caution in diabetes mellitus
• Caution in elderly patients
• Monitor electrolytes regularly
• Caution in patients with a history of acute porphyrias
• Caution in hepatic disorders

Pregnancy

No information available; use with caution and consult healthcare professional.

Breast-feeding

Avoid; no information regarding safety in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• 2.5 mg immediate-release tablet
• 1.5 mg modified-release tablet

Mechanism of action

Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter, leading to reduced sodium reabsorption. As a result, sodium and water are retained in the lumen of the nephron for urinary excretion. The effects that follow include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure. Interestingly, it is likely that thiazide-like diuretics such as indapamide have additional blood pressure lowering mechanisms that are unrelated to diuresis. This is exemplified by the observation that the antihypertensive effects of thiazides are sustained 4-6 weeks after initiation of therapy, despite recovering plasma and extracellular fluid volumes. Some studies have suggested that indapamide may decrease responsiveness to pressor agents while others have suggested it can decrease peripheral resistance. Although it is clear that diuresis contributes to the antihypertensive effects of indapamide, further studies are needed to investigate the medication’s ability to decrease peripheral vascular resistance and relax vascular smooth muscle.

Pharmacodynamics

Classified as a sulfonamide diuretic, indapamide is an effective antihypertensive agent and by extension, has shown efficacy in the prevention of target organ damage. Administration of indapamide produces water and electrolyte loss, with higher doses associated with increased diuresis. Severe and clinically significant electrolyte disturbances may occur with indapamide use - for example, hypokalemia resulting from renal potassium loss may lead to QTc prolongation. Further electrolyte imbalances may occur due to renal excretion of sodium, chloride, and magnesium. Other indapamide induced changes include increases in plasma renin and aldosterone, and reduced calcium excretion in the urine. In many studies investigating the effects of indapamide in both non-diabetic and diabetic hypertensive patients, glucose tolerance was not significantly altered. However, additional studies are necessary to assess the long term metabolic impacts of indapamide, since thiazide related impaired glucose tolerance can take several years to develop in non-diabetic patients.