Hypertension, essential arterial disease

Orally.

One tablet per 24 hours, preferably in the morning. It must be swallowed, whole with a glass of water, it must not be chewed or chewed. Higher doses do not improve the antihypertensive action of indapamide but increase its salidiuretic effect.

Renal Insufficiency (see sections Contraindications and Warnings and Precautions)

In patients with severe renal insufficiency (creatinine clearance
Film-coated tablet, biconvex, round and white, engraved, "1.5" on one side without inscription on the other side

Class: Pharmacotherapeutic: Sulfonamides, alone. Code: ATC: C03 BA11

Indapamide is an indole-derived sulfamide derivative, related to pharmacologically active thiazide diuretics, which acts by inhibiting sodium reabsorption at the cortical dilution segment. It increases the urinary excretion of sodium and chlorides and, to a lesser degree, the excretion of potassium and magnesium, thus increasing diuresis and exerting an antihypertensive action.

Phase II and III studies showed an antihypertensive effect in monotherapy that lasted 24 hours. It appears in doses, where its diuretic properties appear only feebly.

Its antihypertensive activity is related to an improvement of the arterial compliance and a decrease of the resistances, total and arterial peripherals.
Indapamide reduces left ventricular hypertrophy

There is a plateau of the antihypertensive effect of thiazide diuretics and related to a certain dose, while undesirable effects continue to increase: in case of ineffective treatment, do not seek to; Increase the doses.

In addition, it has been demonstrated in the short, medium and long term in hypertension that indapamide
· Respects lipid metabolism, triglycerides, LDL-cholesterol and HDL-cholesterol

· Respects carbohydrate metabolism even in diabetic hypertensive patients

Indapamide has a minor or moderate influence on the ability to drive and use machines

Indapamide does not alter vigilance but individual reactions in relation to a lowering of blood pressure may occur in some patients, especially at the beginning of treatment or in combination with another antihypertensive drug.

Therefore, the ability to drive or use machinery may be impaired.


· Severe renal impairment

· Hepatic encephalopathy or severe hepatic insufficiency

· Hypokalemia.

Warnings

In the case of hepatic impairment, thiazide-related diuretics may induce hepatic encephalopathy, particularly in the case of electrolyte imbalance. In this case, the administration of the diuretic must be immediately interrupted.
Photosensitivity

Cases of photosensitivity reactions have been reported with thiazide and related diuretics (see section 4.4 Undesirable effects). If a photosensitivity reaction occurs during treatment, it is recommended to discontinue the treatment. If a new administration of the diuretic proves necessary, it is recommended to protect the parts of the body exposed to sunlight or UVA light.

Excipients

In patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases), treatment with Indapamide is not recommended.
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Special precautions for use

Balance, hydro-electrolytic

· Natrémie

It must be checked before starting treatment and then at regular intervals. Any treatment, diuretic can cause hyponatremia with sometimes very serious consequences. Since the decline in serum sodium may initially be asymptomatic, regular monitoring is essential and should be even more prevalent in elderly and cirrhotic patients (see sections Effects, Undesirable and Overdose)
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· Kalémie

Potassium depletion with hypokalaemia is the major risk of thiazide and related diuretics. The risk of occurrence of hypokalemia (
In all cases, more frequent checks of serum potassium are necessary. The first potassium test should be carried out during the first week following the initiation of treatment.
The finding of hypokalaemia requires its correction

· Calcémie

Thiazide and related diuretics may decrease the urinary excretion of calcium and result in a slight and transient increase in serum calcium. A frank hypercalcemia may be related to an unrecognized hyperparathyroidism

Discontinue treatment before exploring parathyroid function

· Blood glucose

It is important for diabetics to control blood glucose, especially in the presence of hypokalemia.

· Uric acid

The trend in gout access can be increased in patients with hyperuricemia

Renal function and diuretics

Thiazide and related diuretics are only fully effective when renal function is normal or poorly altered (serum creatinine less than 25 mg / l or 220 μmol / l in adults). In the elderly, serum creatinine should be readjusted according to age, weight and sex.

Hypovolemia, secondary to the hydrosodic loss induced by the diuretic at the start of treatment, results in a reduction in glomerular filtration. This may result in increased blood urea and serum creatinine. This transient functional renal failure is of no consequence in the subject, with normal renal function but may aggravate a pre-existing renal insufficiency

· Sportsmen

The attention of athletes is drawn to the fact that this medicinal product contains an active ingredient which can induce a positive reaction from the tests carried out during the anti-doping tests. >
Associations, deprecated

+; Lithium

Increased lithyemia with signs of overdose, such as during a diet, deodorized (decreased urinary excretion of lithium). However, if the use of diuretics is necessary, strict monitoring of lithium and dosage adjustment is necessary.

Associations subject to precautions for use

+ Drugs which can induce torsades of tip

· Anti-arrhythmic class Ia (quinidine, hydroquinidine, disopyramide)

· Anti-arrhythmic class III (amiodarone, sotalol, dofetilide, ibutilide)

· Some antipsychotics: Phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine)
· Benzamides (amisulpride, sulpiride, sultopride, tiapride)

· Butyrophenones (droperidol haloperidol)

· Other: bepridil, cisapride, diphenemil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV.
Increased risk of ventricular arrhythmia, in particular torsades de pointe (hypokalaemia is a risk factor).

Hypokalemia should be monitored and corrected if necessary before introducing an association. The clinic, electrolytes, plasma and ECG should be monitored.

Use substances which do not present a risk of torsades of peak in case of hypokalaemia

+ NSAIDs, including inhibitors, selective COX-2, acetylsalicylic acid, high dose (≥3 g / day) >
Possible decrease in effect, antihypertensive agent of indapamide.

Risk of renal insufficiency, acute in dehydrated patients (decrease, glomerular filtration). Moisturize the patient, monitor renal function at the beginning of treatment.

+; Angiotensin converting enzyme (ACE) inhibitors

Risk of sudden hypotension, acute renal failure and / or acute renal insufficiency upon initiation of IEC treatment in case of pre-existing sodium depletion (especially in patients with stenosis, artery Kidney disease).
In high blood pressure, when the previous diuretic treatment may have caused sodium depletion, it is necessary

· Either stop the diuretic 3 days before the start of treatment with IEC and reintroduce a hypokalemic diuretic if necessary

· Or administering low initial doses of IEC and increasing them gradually

In congestive heart failure, start with a very low dose of IEC, possibly after, reducing the dose of the diuretic, hypokalaemic associated.


+ Other hypokalaemic agents: amphotericin B (IV), gluco- and mineralo-corticoids (pathway, systemic), tetracosactide, stimulant laxatives
Increased risk of hypokalemia (additive effect).

Monitoring of serum potassium and, if necessary, correction, to be taken into account in case of digital therapy. Use non-stimulating laxatives.

+; Baclofen

Increased effect, antihypertensive.

Moisturize the patient, monitor renal function at the beginning of treatment.

+ Digital Preparations

Hypokalemia favors the toxic effects of digitalis.

Monitoring of serum potassium and ECG and, if necessary, adjusting the treatment.

Associations to be taken into account

+ Hyperkalaemic diuretics (amiloride, spironolactone, triamterene)

In the case of a rational combination, useful for some patients, the occurrence of hypokalaemia or hyperkalaemia (especially in patients with renal insufficiency or diabetes) can not be excluded. Kalemia and ECG should be monitored and, if necessary, reconsider treatment.

+; Metformine

Increased risk of metformin-induced lactic acidosis, triggered by possible renal insufficiency associated with association with diuretics and more particularly with loop diuretics. Do not use metformin when: serum creatinine exceeds 15 mg / l (135 μmol / l) in humans and 12 mg / l (110 μmol / l) in women.

+ Iodinated contrast media

In case of dehydration, caused by diuretics, increased risk of acute renal failure, especially when using high doses of iodinated contrast media
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Rehydration before administration of the iodinated product

+ Antidepressants imipraminic, neuroleptic

Antihypertensive effect and risk, plus orthostatic hypotension (additive effect)

+; Calcium (salts of)

Risk of hypercalcaemia by decreased urinary excretion of calcium

+; Ciclosporin, Tacrolimus

Risk of increased serum creatinine without any change in circulating levels of ciclosporin, even in the absence of depletion,


Decreased antihypertensive effect (hydrosodic retention due to corticosteroids).

Without object.

Indapamide has not shown toxicity up to 40 mg, that is 27 times the therapeutic dose.

Signs of acute intoxication occur mostly by hydro-electrolyte disorders (hyponatremia, hypokalaemia) .At the clinical level, nausea, vomiting, hypotension, arterial, cramps, dizziness, somnolence, state, confusion, polyuria Or oliguria up to and including anuria (by hypovolemia).

The first measures consist in: rapidly eliminating the substance (s) ingested by gastric lavage and / or administration of activated carbon and then restoring the equilibrium, hydro-electrolyte in a specialized center, until normalization. >

Pregnancy

In general, the administration of diuretics should be avoided in pregnant women and should never constitute the treatment of the physiological edema of pregnancy. Diuretics may cause foetoplacental ischemia with a risk of hypotrophy, fetal.

Breastfeeding

Breast-feeding is not recommended (indapamide passes into milk, maternal).

Most clinical and / or biological adverse effects are dose-dependent.

Thiazides, including indapamide, may cause the following undesirable effects in order of decreasing frequency

(> 1 / 10,000, 1/10,