Vazamide SR

Indapamide (Vazamide SR) 1.5 mg Sustained-Release Tablet is a white to off white round biconvex film coated tablet.
Each sustained-release tablet contains indapamide 1.5 mg.

Pharmacology: Pharmacodynamics: Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to thiazide diuretics, which acts by inhibiting the reabsorption of sodium in the cortical dilution segment. It increases the urinary excretion of sodium and chlorides and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing urine output and having an antihypertensive action.
Pharmacokinetics: Absorption: Indapamide is rapidly and completely absorbed from the gastrointestinal tract. Meals slightly increase the rate of absorption, but do not have any influence on the quantity of drug absorbed. Peak plasma concentrations occur approximately 12 hours after a single dose. Repeated dosing limits variations in plasma concentrations between 2 doses. lntraindividual variability exists.
Distribution: Binding of Indapamide to plasma proteins is 79%. The elimination half-life is between 14 to 24 hours (mean 18 hours). The steady state is reached after 7 days. Repeated dosing does not induce accumulation.
Metabolism: Indapamide is extremely metabolized in the liver.
Elimination: About 70% of the dose has been reported to be excreted in the urine and about 22% is excreted in the feces in the form of inactive metabolites.

Indapamide is indicated in the management of mild to moderate hypertension and also for edema, including that associated with heart failure.

One tablet once daily, preferably in the morning. The tablets can be taken irrespective of meals and should be swallowed whole with water.
Do not crush or chew.
If in case patient forgets to take a dose of the medicine, take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose. Or as prescribed by the physician.

Signs of acute poisoning take the form above all of water/electrolyte disturbances (hyponatraemia, hypokalaemia) which are manifested as nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusion, polyuria or oliguria possibly to the point of anuria (due to hypovolaemia).
Initial measures involve the rapid elimination of the ingested substance(s) by gastric wash-out and for administration of activated charcoal, followed by restoration of water/electrolyte balance to normal in a specialized center.

Indapamide is contraindicated in: Individuals who are hypersensitive to Indapamide or other sulphonamide type medications.
Severe hepatic failure or hepatic encephalopathy.
Severe renal failure with creatinine clearance below 30 mL/min.

Patients with Hepatic Impairment: Use of thiazide diuretics may cause hepatic encephalopathy, particularly in case of electrolyte imbalance. Administration of the diuretic must be stopped immediately.
Photosensitivity: Cases have been reported with the use of thiazide and thiazide-related diuretics. Immediately stop the treatment and if use of diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or artificial UVA.
Patients with Rare Hereditary Problems: This formulation contains ingredients that is not recommended for patients with rare hereditary problem such as galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Water to Electrolyte Balance - Plasma Sodium: Plasma Sodium must be monitored regularly especially in the elderly and cirrhotic patients (asymptomatic fall in plasma sodium). All diuretics may cause hyponatremia. Dehydration and orthostatic hypolension may be caused by hyponatremia with hypovolemia. Slight incidence of Secondary Compensatory metabolic alkalosis due to concomitant loss of chloride ions were observed.
Water to Electrolyte Balance - Plasma Potassium: Potassium depletion with hypokalemia is the major risk of thiazide and related diuretics. Regular monitoring is advised especially in the elderly, malnourished, poly-medicated patients, cirrhotic patients with edema and ascites, and coronary artery disease and cardiac failure patients as Indapamide may increase cardiac toxicity of digitalis and risks of arrhythmias (Patients with long QT Interval is at risk whether the origin is congenital or latrogenic). Bradycardia caused by hypokalemia, may onset severe arrhythmia, particularly potentially fatal torsades de pointes. Frequent monitoring of plasma potassium is advised in all the situations mentioned previously.
Water to Electrolyte Balance - Plasma Calcium: Thiazide diuretics may decrease urinary calcium elimination and may cause a slight transitory rise in plasma calcium. Sudden hypercalcemia may be due to previously unrecognized hyperparathyroidism. Withdrawal from treatment is advised before Investigating parathyroid functions.
Blood Glucose: Frequent monitoring of blood glucose is advised in diabetic patients for presence of hypokalemia.
Uric Acid: Use of indapamide in hyperuricemic patients may increase tendency of gout attacks.
Renal Functions and Diuretics: Thiazide and related diuretics are fully effective only when renal function is normal or only minimally impaired (plasma creatinine levels <25 mg/L). Dosage adjustment may be required in the elderly. Hypovolemia due lo loss of water and sodium induced by a diuretic may cause a reduction in the glomerular filtration leading to an increase in blood urea and plasma creatinine. The transitory functional renal insufficiency may worsen in patients with preexisting renal insufficiency.
Athletes: Use of Indapamide may render a positive reaction in doping test.
Effects on the Ability to Drive or Operate Machinery: Indapamide does not affect vigilance but different reactions in relation with the decrease in blood pressure may occur in individual cases, especially at the start of the treatment or when another antihypertensive agent is added. As a result, the ability to drive vehicles or to operate machinery may be impaired.

Pregnancy: As a general rule, the administration of diuretics should be avoided in pregnant women and should never be used to treat physiological edema of pregnancy. Diuretics can cause fetoplacenlal ischemia, with a risk of impaired fetal growth.
Lactation: Thiazide Diuretics have been associated, during breastfeeding, with decrease or even suppression of milk lactation. There is lack of studies on the possible excretion of indapamide or its metabolites in human milk and hypersensitivity to sulfonamide-derived medicines and hypokalemia might occur, a risk to the infant cannot be excluded.

In general, most adverse effects are mild and transient with the most frequently reported being giddiness, diarrhea, headache, anorexia, gastric irritation, nausea, vomiting, abdominal pain usually occurring within the first month of treatment. Electrolyte imbalances including hypochloraemic alkalosis, hyponatraemia, hypokalaemia and hyperuricaemia. Signs of electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain and cramps, seizures, oliguria, hypotension, and gastrointestinal disturbances. Hypersensitivity reactions which include skin rashes, pulmonary edema, pneumonitis, cholestatic jaundice, pancreatitis and blood dyscrasias including thrombocytopenia and less frequently granulocytopenia, leucopenia, aplastic anemia and haemolytic anaemia have been reported. Serum potassium should be monitored in patients with a history of gout, who should continue to receive appropriate treatment. Other adverse effects include vertigo, fatigue, dizziness, muscle weakness, paraesthesia, syncope, visual impairment, hypotension, arrhythmia, torsade de pointes (potentially fatal), constipation, angioedema, urticaria and renal failure. The table as follows shows some undesirable effects which have been observed with indapamide during treatment. (See table.)

Click on icon to see table/diagram/image

Lithium: Concomitant use of diuretics with lithium is not recommended. Careful monitoring of plasma lithium and dose adjustment is required if use of diuretics is necessary.
Torsade de pointes-inducing drugs: Class Ia Antiarrhythmics (quinidine, hydroquinidine, and disopyramide), Class III Antiarrhythmics (amiodarone, sotalol, dofetilide, and ibutilide).
Antipsychotics: Phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, and trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, and tiapride), and butyrophenones (droperidol and haloperidol). These agents increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor). Plasma electrolytes and ECG monitoring is advised if this combination is used.
NSAIDs (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (≥3 g/day): Concomitant use may decrease the antihypertensive effect of Indapamide. Risk of acute renal failure in dehydrated patients caused by decrease glomerular filtration may occur. Hydrate the patient and monitor renal function.
A.C.E. Inhibitors: Risk of sudden hypotension and/or acute renal failure when treatment with an A.C.E. is initiated in the presence of pre-existing sodium depletion (particularly in patients with renal artery stenosis). Stop diuretic 3 days before starting treatment with A.C.E. inhibitor, and restart a hypokalemic diuretic if necessary; or gradual increment in dosing of A.C.E. inhibitors. In CHF patients, dose adjustment is required if concomitant use with hypokalemic diuretic. Monitor renal function (plasma creatinine) during the first weeks of treatment.
Potassium-depleting Drugs: Use of agents such as Amphotericin B (IV), gluco- and mineralo-corticoids (systemic route), stimulant laxatives, and tetracosactide may increase risk of hypokalemia (additive effect). Monitor plasma potassium and correct, if required. Use non-stimulant laxatives.
Baclofen: Concomitant use may increase the antihypertensive effect of Indapamide. Hydrate the patient and monitor renal function.
Digitalis Preparations: Adjust treatment and/or monitor plasma potassium and ECG as hypokalemia may increase risk to exposure of the toxic effects of digitalis, if used with diuretics.
Allopurinol: Concomitant treatment with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.
Potassium-sparing Diuretics (Amiloride, Spironolactone, and Triamterene): Occurrence of hypokalemia/hyperkalemia particularly in patients with renal failure or diabetes is increased. Plasma potassium and ECG should be monitored.
Metformin: Increased risk of metformin-induced lactic acidosis due to the possibility of functional renal failure associated with diuretics (loop diuretics). Concomitant use of Indapamide with metformin should be avoided if plasma creatinine exceeds 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.
lmipramine-like Antidepressants (Neuroleptics): Concomitant use with these agents may cause an additive effect of the antihypertensive effects of Indapamide increasing risk of orthostatic hypotension.
Calcium (Salts): Decreased urinary elimination of calcium may increase risk of hypercalcemia.
Ciclosporin and Tacrolimus: Risk of increased plasma creatinine without any change in circulating cyclosporin levels, even in the absence of water/sodium depletion.
Corticosteroids and Tetracosactide (Systemic route): Concomitant use may lead to decreased antihypertensive effect of Indapamide due to water/sodium retention caused by corticosteroids.

Store at temperatures not exceeding 30°C.

Diuretics

C03BA11 - indapamide ; Belongs to the class of low-ceiling sulfonamide diuretics.

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