NATRILIX SR Indapamide 1.5mg Sustained Release Tablet 30's

Treatment of essential hypertension.

 

Hypersensitivity to the active substance, to other sulfonamides or to any of the excipients. Severe renal failure. Hepatic encephalopathy or severe impairment of liver function. Hypokalemia.

 

Overdosage

May be taken with or without food: Preferably taken in the morning. Swallow whole w/ water, do not chew/crush.

Hypersensitivity to the active substance, to other sulfonamides or to any of the excipients. Severe renal failure. Hepatic encephalopathy or severe impairment of liver function. Hypokalemia.

Special warnings: When liver function is impaired, thiazide-related diuretics may cause hepatic encephalopathy, particularly in case of electrolyte imbalance. Administration of the diuretic must be stopped immediately if this occurs.
Photosensitivity: Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics. If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a readministration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA. Excipients: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Special precautions for use: Water and electrolyte balance: Plasma sodium: This must be measured before starting treatment, then at regular intervals subsequently. The fall in plasma sodium may be asymptomatic initially and regular monitoring is therefore essential, and should be even more frequent in the elderly and cirrhotic patients. Any diuretic treatment may cause hyponatremia, sometimes with very serious consequences. Hyponatremia with hypovolemia may be responsible of dehydration and orthostatic hypotension. Concomitant loss of chloride ions may lead to secondary compensatory metabolic alkalosis: the incidence and degree of this effect are slight.
Plasma potassium: Potassium depletion with hypokalemia is the major risk of thiazide and related diuretics. The risk of onset of hypokalemia (<3.4 mmol/l) must be prevented in certain high risk populations, i.e. the elderly, malnourished and/or polymedicated, cirrhotic patients with edema and ascites, coronary artery disease and cardiac failure patients. In this situation, hypokalemia increases the cardiac toxicity of digitalis preparations and the risks of arrhythmias.
Individuals with a long QT interval are also at risk, whether the origin is congenital or iatrogenic. Hypokalemia, as well as bradycardia, is then a predisposing factor to the onset of severe arrhythmias, in particular, potentially fatal torsades de pointes.
More frequent monitoring of plasma potassium is required in all the situations indicated above. The first measurement of plasma potassium should be obtained during the first week following the start of treatment.
Detection of hypokalemia requires its correction.
Plasma calcium: Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transitory rise in plasma calcium. Frank hypercalcemia may be due to previously unrecognized hyperparathyroidism. Treatment should be withdrawn before the investigation of parathyroid function.
Blood glucose: Monitoring of blood glucose is important in diabetics, in particular in the presence of hypokalemia.
Uric acid: Tendency to gout attacks may be increased in hyperuricemic patients.
Renal function and diuretics: Thiazide and related diuretics are fully effective only when renal function is normal or only minimally impaired (plasma creatinine below levels of the order of 25 mg/l, i.e. 220 μmol/l in an adult). In the elderly, this plasma creatinine must be adjusted in relation to age, weight and gender. Hypovolemia, secondary to the loss of water and sodium induced by the diuretic at the start of treatment causes a reduction in glomerular filtration. This may lead to an increase in blood urea and plasma creatinine. This transitory functional renal insufficiency is of no consequence in individuals with normal renal function but may worsen preexisting renal insufficiency.
Athletes: The attention of athletes is drawn to the fact that this medicinal product contains a drug substance, which may give a positive reaction in doping tests.
Drivers and machine operators: 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.

 

Use In Pregnancy & Lactation

Summary of safety profile: The most commonly reported adverse reactions are hypersensitivity reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions and maculopapular rashes. During clinical trials, hypokalemia (plasma potassium <3.4 mmol/l) was seen in 10% of patients and <3.2 mmol/l in 4 % of patients after 4 to 6 weeks treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.23 mmol/l. The majority of adverse reactions concerning clinical or laboratory parameters are dose-dependent. Tabulated summary of adverse reactions: The following undesirable effects have been observed with indapamide during treatment ranked under the following frequency: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (≥1/100,000 to <1/10,000), not known (cannot be estimated from the available data). See table.

 

Combinations that are not recommended: Lithium: Increased plasma lithium with signs of overdosage, as with a salt-free diet (decreased urinary lithium excretion). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dose adjustment are required.
Combinations requiring precautions for use: Torsades de pointes-inducing drugs: Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide), class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics eg, phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride) butyrophenones (droperidol, haloperidol), others eg, bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV. Increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor). Monitor for hypokalemia and correct, if required, before introducing this combination. Clinical, plasma electrolytes and ECG monitoring. Use substances which do not have the disadvantage of causing torsades de pointes in the presence of hypokalemia.
NSAIDs (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (≥3 g/day): Possible reduction in the antihypertensive effect of indapamide. Risk of acute renal failure in dehydrated patients (decreased glomerular filtration). Hydrate the patient; monitor renal function at the start of treatment.
Angiotensin converting enzyme (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).
In hypertension, when prior diuretic treatment may have caused sodium depletion, it is necessary: Either to stop the diuretic 3 days before starting treatment with the A.C.E. inhibitor, and restart a hypokalemic diuretic if necessary; or give low initial doses of the A.C.E. inhibitor and increase the dose gradually.
In congestive heart failure, start with a very low dose of A.C.E. inhibitor, possibly after a reduction in the dose of the concomitant hypokalemic diuretic. In all cases, monitor renal function (plasma creatinine) during the first weeks of treatment with an A.C.E. inhibitor.
Other compounds causing hypokalemia: Amphotericin B (IV), gluco- and mineralo-corticoids (systemic route), tetracosactide, stimulant laxatives: Increased risk of hypokalemia (additive effect). Monitoring of plasma potassium and correction if required. Must be particularly borne in mind in case of concomitant digitalis treatment. Use non-stimulant laxatives.
Baclofen: Increased antihypertensive effect. Hydrate the patient; monitor renal function at the start of treatment.
Digitalis preparations: Hypokalemia predisposing to the toxic effects of digitalis. Monitoring of plasma potassium and ECG and, if necessary, adjust the treatment.
Combinations requiring special care: Allopurinol: Concomitant treatment with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.
Combinations to be taken into consideration: Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Whilst rational combinations are useful in some patients, hypokalemia or hyperkalemia (particularly in patients with renal failure or diabetes) may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.
Metformin: Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics. Do not use metformin when plasma creatinine exceeds 15 mg/L (135 μmol/L) in men and 12 mg/l (110 μmol/L) in women.
Iodinated contrast media: In the presence of dehydration caused by diuretics, increased risk of acute renal failure, in particular when large doses of iodinated contrast media are used. Rehydration before administration of the iodinated compound.
Imipramine-like antidepressants, neuroleptics: Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).
Calcium (salts): Risk of hypercalcemia resulting from decreased urinary elimination of calcium.
Ciclosporin, tacrolimus: Risk of increased plasma creatinine without any change in circulating cyclosporin levels, even in the absence of water/sodium depletion. Corticosteroids, tetracosactide (systemic route): Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Storage

Action

Diuretics