Natrilix^® SR

Indapamide 1.5mg

Presentation and composition
Box of 30 sustained-release coated tablets dosed at 1.5 mg of Indapamide.

Pharmacology
Indapamide is a diuretic acting at the cortical dilution segment. The antihypertensive action is related to an improvement in arterial compliance and a reduction in arteriolar and total peripheral resistance. Indapamide also reduces left ventricular hypertrophy.

Pharmacokinetics
Natrilix SR is supplied in a sustained release dosage based on a matrix system in which the active ingredient is dispersed in a support which allows sustained release of indapamide.

Absorption
The fraction of indapamide released is rapidly and totally absorbed via the gastrointestinal digestive tract.

Eating slightly increases the rapidity of absorption but has no influence on the amount of the drug absorbed.

Peak serum level following a single dose occurs about 12 hours after ingestion, repeated administration reduces the variation in serum levels between 2 doses.

Intra-individual variability exists.

Distribution
Binding of indapamide to plasma proteins is 79 %. The plasma elimination half-life is 14 to 24 hours (mean 18 hours).

Steady state is achieved after 7 days.

Repeated administration does not lead to accumulation.

Metabolism
Elimination is essentially urinary (70 % of the dose) and faecal (22 %) in the form of inactive metabolites.

Population at risk
Pharmacokinetic parameters are unchanged in renal failure patients.

Indication
Treatment of essential hypertension.

Adverse Effects
The majority of adverse effects are dose dependent. Thiazide and related diuretics including Indapamide may cause:

• Variations in certain blood parameters, in particular potassium depletion, hyponatraemia with hypovolaemia responsible for dehydration
and orthostatic hypotension, increase in plasma uric acid and glucose.

• According to clinical parameters:
  - in the presence of hepatic insufficiency, possible onset of hepatic encephalopathy may occur;
  - hypersensitive reactions essentially dermatological;
  - maculopapular rashes, purpura, possible worsening of pre-existent acute disseminated lupus erythematosus;
  - nausea, constipation, dry mouth, vertigo, tired ness, paresthesiae, headache, occurring rare ly and responding in most instances to a dose reduction;
  - very rarely, pancreatitis.

Warning
Administration of the diuretic must be stopped immediately when liver function is impaired.

Precautions
This drug should be used cautiously in the following situations: disturbed water/electrolyte balance (plasma sodium, plasma potassium), diabetes, gout, kidney problems.

Athletes
The attention of athletes is drawn to the fact that this drug contains an active ingredient that may induce a positive reaction during antidoping control tests.

Contraindications
• Hypersensitivity to sulphonamides.
• Severe renal failure.
• Hepatic encephalopathy or severe liver failure.
• Hypokalemia.

Pregnancy
As a general rule, the administration of thiazide and related diuretics should be avoided in pregnant women and should never be used to treat physiological oedema of pregnancy. Diuretics can cause faetoplacental ischemia, with a risk of foetal hypotrophy.

Breast-Feeding
Breast-feeding is inadvisable (passage into breast milk).

Drug Interactions and Other Interactions

Inadvisable combinations:
Lithium, non-antiarrhythmic drugs causing wave burst arrhythmias.

Combinations requiring precautions:
NSAID (systemic), high dose salicylate, other hypokalemic compounds, baclofen, digitalis preparations.

Combinations which must be taken into account Hyperkalemic diuretics, angiotensin converting enzyme inhibitors, antiarrhythmic agents causing wave burst arrhythmias, metformin, iodinated contrast media, imipramine antidepressants (tricyclics), neuroleptics, calcium salts, cyclosporin, corticosteroids, tetracosaclide (systemic).

Drivers and use of machinery
Individual reactions in relation to the decrease in blood pressure may occur in certain patients. Consequently, the ability to drive vehicles or to use machinery may be decreased.

Recommended Dosage
Oral route.
One tablet per 24 hours, preferably in the morning. Higher doses do not improve the antihypertensive action of Indapamide, rather they increase the saludiuretic effect.

Overdosage
Indapamide has not shown any toxicity at doses of up to 40 mg, i.e. 27 times the therapeutic dose. Above all, signs of acute poisoning take the form of water and electrolyte disturbances (hyponatraemia and hypokalemia). Clinically, they include possible nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusional states, polyuria or oliguria up to the extent of anuria (due to hypovolaemia).

Initial measures taken involve the rapid elimination of the product(s) ingested by means of gastric lavage and/or the administration of activated charcoal, followed by restoration of the fluid and electrolyte balance to normal in a specialised centre.

Storage
Do not exceed the expiry date clearly indicated on the outer packaging.
Store at room temperature, 15-25°C. Protect from humidity.