Indapamide

Indapamide is an antihypertensive agent belonging to Thiazide Diuretics.

Indapamide is a thiazide diuretic used for the treatment of high blood pressure, as well as edema caused by heart diseases.

The bioavailability of Indapamide is about 93% after an oral dose and is unaffected by food or antacids. The Tmax occurs approximately 2.3 hours after oral administration. Approximately 76-79% of Indapamide is protein bound. In the blood, indapamide is extensively and preferentially bound to erythrocytes. Indapamide undergoes extensive metabolism in the liver, the majority of indapamide excreted is metabolized, with only 7% remaining unchanged. An estimated 60-70% of indapamide is eliminated in the urine, while 16-23% is eliminated in the feces.

Indapamide shows common side effects Increased urination, Dry mouth, Hypotension, Itching or rash, dizziness, headache, Irregular heartbeat, etc.

Indapamide is available in the form of Oral Tablets.

Indapamide is available in India, Europe, Austria, Slovenia, China, and Italy.

Indapamide belonging to the Thiazide Diuretics acts as an antihypertensive agent.

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.

The onset of action of Indapamide occurs within 1-3 hours of its administration.

The Duration of Action for Indapamide in the body is approximately 8-12 hours.

The Tmax was found within 2 hours and Cmax 140 ng/mL following the administration of Indapamide.

Indapamide comes as an Oral Tablet taken by mouth. It is usually taken once a day in the morning. Don't take this drug too close to bedtime, otherwise, it will result in frequent urination. It is best to take this medication at least 4 hours before bedtime.

Indapamide is a thiazide diuretic used for the treatment of high blood pressure, as well as edema caused by heart diseases. It should be used with caution in patients with severe kidney diseases due to the increased risk of severe side effects.

Indapamide is an antihypertensive agent belonging to Thiazide Diuretics.

Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule. The effects of Indapamide include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure. It works by increasing the frequency of urination. This helps the body get rid of extra salt and water. This can lessen symptoms such as shortness of breath or swelling in the ankles or feet.

Indapamide is approved for use in the following clinical indications

• Edema

Indapamide is also indicated for the treatment of salt and fluid retention associated with congestive heart failure.

• Hypertension

Indapamide is indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs.

• Edema

The adult starting indapamide dose for edema of congestive heart failure is 2.5 mg as a single daily dose taken in the morning. If the response to 2.5 mg is not satisfactory after one week, the daily dose may be increased to 5.0 mg taken once daily. If the antihypertensive response to indapamide is insufficient, Indapamide may be combined with other antihypertensive drugs, with careful monitoring of blood pressure.

It is recommended that the usual dose of other agents be reduced by 50% during initial combination therapy. As the blood pressure response becomes evident, further dosage adjustments may be necessary. In general, doses of 5.0 mg and larger have not appeared to provide additional effects on blood pressure or heart failure but are associated with a greater degree of hypokalemia. There is a minimal clinical trial experience in patients with doses greater than 5.0 mg once a day.

• Hypertension

The adult starting indapamide dose for hypertension is 1.25 mg as a single daily dose taken in the morning. If the response to 1.25 mg is not satisfactory after 4 weeks, the daily dose may be increased to 2.5 mg taken once daily. If the response to 2.5 mg is not satisfactory after 4 weeks, the daily dose may be increased to 5.0 mg taken once daily but adding another antihypertensive should be considered.

Indapamide is available in various strengths as 1.25mg and 2.5mg.

Indapamide is available in the form of Oral Tablets.

Avoid consumption of a high-salt or high-sodium diet while taking Indapamide.

Indapamide is contraindicated in patients with

• Anuria
• Hypersensitivity to Indapamide or to other sulfonamide-derived drugs.

• Hypokalemia

The risk of hypokalemia secondary to diuresis and natriuresis is increased when larger doses are used when the diuresis is brisk when severe cirrhosis is present and during concomitant use of corticosteroids or ACTH. Interference with adequate oral intake of electrolytes will also contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis, such as increased ventricular irritability.

• Hyponatremia

Dilutional hyponatremia may occur in edematous patients; the appropriate treatment is a restriction of water rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. However, in actual salt depletion, appropriate replacement is the treatment of choice. Any chloride deficit that may occur during treatment is generally mild and usually does not require specific treatment except in extraordinary circumstances such as liver or renal disease.

• Hypomagnesemia

Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

• Hyperuricemia and Gout

Serum concentrations of uric acid increased by an average of 0.69 mg/100 mL in patients treated with indapamide 1.25 mg, and by an average of 1.0 mg/100 mL in patients treated with indapamide 2.5 mg and 5.0 mg, and frank gout may be precipitated in certain patients receiving indapamide. Serum concentrations of uric acid should, therefore, be monitored periodically during treatment.

• Glucose Tolerance

Latent diabetes may manifest and insulin requirements in diabetic patients may be altered during thiazide administration. A mean increase in the glucose of 6.47 mg/dL was observed in patients treated with indapamide 1.25 mg, which was not considered clinically significant in these trials. Serum concentrations of glucose should be monitored routinely during treatment with Indapamide.

• Calcium Excretion

Calcium excretion is decreased by diuretics pharmacologically related to indapamide. After six to eight weeks of indapamide 1.25 mg treatment and in long-term studies of hypertensive patients with higher doses of indapamide, however, serum concentrations of calcium increased only slightly with indapamide. Prolonged treatment with drugs pharmacologically related to indapamide may in rare instances be associated with hypercalcemia and hypophosphatemia secondary to physiologic changes in the parathyroid gland; however, the common complications of hyperparathyroidism, such as renal lithiasis, bone resorption, and peptic ulcer, have not been seen. Treatment should be discontinued before tests for parathyroid function are performed. Like thiazides, indapamide may decrease serum PBI (Protein-bound Iodine) levels without signs of thyroid disturbance.

• Interaction With Systemic Lupus Erythematosus

Thiazides have exacerbated or activated systemic lupus erythematosus and this possibility should be considered with indapamide as well.

Consumption of alcohol is not recommended while taking Indapamide medicine. The combination may increase the risk of dizziness, fainting, and very low blood pressure.

It is not known whether this drug is excreted in human milk. Because most drugs are excreted in human milk, if the use of this drug is deemed essential, the patient should stop nursing.

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes the mother and fetus to unnecessary hazards. Diuretics do not prevent the development of toxemia in pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Avoid consumption of a high-salt or high-sodium diet while taking Indapamide.

• Common Adverse effects

Dizziness, weakness, tiredness, back pain, muscle cramps, feeling anxious or agitated, headache, runny nose.

• Rare Adverse effects

Drowsiness, lack of energy, feeling tired, leg cramps, muscle weakness or limp feeling, severe weakness, loss of coordination, feeling unsteady, fast or irregular heartbeats, fluttering in your chest, feeling restless, numbness or tingling, vomiting, constipation.

• Other Antihypertensives

Indapamide may add to or potentiate the action of other antihypertensive drugs. In limited controlled trials that compared the effect of Indapamide combined with other antihypertensive drugs with the effect of the other drugs administered alone, there was no notable change in the nature or frequency of adverse reactions associated with the combined therapy.

• Norepinephrine

Indapamide, like thiazides, may decrease arterial responsiveness to norepinephrine, but this diminution is not sufficient to preclude the effectiveness of the pressor agent for therapeutic use.

• Lithium

In general, diuretics should not be given concomitantly with lithium because they decrease its renal clearance and add a high risk of lithium toxicity. Read prescribing information for lithium preparations before use of such concomitant therapy.

• Post-Sympathectomy Patient

The antihypertensive effect of the drug may be enhanced in the post-sympathectomized patient.

The common side of Indapamide includes the following

Common

• Increased urination
• Dry mouth
• Hypotension
• Itching or rash
• Dizziness
• Headache
• Irregular heartbeat

Rare

• Abdominal pain
• Joint pain, stiffness, and swelling
• Muscle cramps
• Loss of appetite
• Nausea and vomiting

• Pregnancy

Teratogenic Effects: Pregnancy Category B

Reproduction studies have been performed in rats, mice, and rabbits at doses up to 6,250 times the therapeutic human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Indapamide. Postnatal development in rats and mice was unaffected by the pretreatment of parent animals during gestation. There are, however, no adequate and well-controlled studies on pregnant women. Moreover, diuretics are known to cross the placental barrier and appear in cord blood. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. There may be hazards associated with this use such as fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult.

• Nursing Mothers

It is not known whether this drug is excreted in human milk. Because most drugs are excreted in human milk, if the use of this drug is deemed essential, the patient should stop nursing.

• Pediatric Use

The safety and effectiveness of Indapamide in pediatric patients have not been established.

• Geriatric Use

Clinical studies of Indapamide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Symptoms of overdosage include nausea, vomiting, weakness, gastrointestinal disorders, and disturbances of electrolyte balance. In severe instances, hypotension and depressed respiration may be observed. If this occurs, support for respiration and cardiac circulation should be instituted. There is no specific antidote. An evacuation of the stomach is recommended by emesis and gastric lavage after which the electrolyte and fluid balance should be evaluated carefully.

Pharmacodynamic

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 nondiabetic patients.

Pharmacokinetics

• Absorption

The bioavailability of Indapamide is about 93% after an oral dose and is unaffected by food or antacids. Indapamide is highly lipid-soluble due to its indoline moiety - a characteristic that likely explains why indapamide’s renal clearance makes up less than 10% of its total systemic clearance. The Tmax occurs approximately 2.3 hours after oral administration. The Cmax and AUC_0-24 values are 263 ng/mL and 2.95 ug/hr/mL, respectively.

• Distribution

Approximately 76-79% of Indapamide is protein bound. Indapamide binds primarily to alpha 1-acid glycoprotein and less significantly to serum albumin and lipoproteins. In the blood, indapamide is extensively and preferentially bound to erythrocytes.

• Metabolism and Excretion

Indapamide of extensive metabolism in the liver, the majority of Indapamide excreted is metabolized, with only 7% remaining unchanged. In humans, as many as 19 distinct indapamide metabolites may be produced, although not all have been identified. An estimated 60-70% of Indapamide is eliminated in the urine, while 16-23% is eliminated in the feces.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018538s028lbl.pdf
• https://go.drugbank.com/drugs/DB00808
• https://www.drugs.com/mtm/indapamide.html
• https://www.practo.com/medicine-info/indapamide-706-api