Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use:

Special warnings:
Hepatic impairment:
When liver function is impaired, thiazide-related diuretics may cause, particularly in case of electrolyte imbalance, hepatic encephalopathy, which can progress to hepatic coma. Administration of the diuretic must be stopped immediately if this occurs.

Excipients
Patients with rare heredity problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Photosensitivity
Cases of photosensitivity have been reported with thiazide and thiazide-related diuretics (see section 4.8). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.

Special precautions for use:
• Water and electrolyte balance:
- Plasma sodium:
This must be measured before starting treatment, then at regular intervals subsequently. Any diuretics treatment may cause hyponatremia, sometimes with very serious consequences. 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 (See sections 4.8 and 4.9).
- Plasma potassium:
Potassium depletion with hypokalemia is the major risk of thiazide and related diuretics. Hypokalaemia may cause muscle disorders. Cases of Rhabdomyolysis have been reported, mainly in the context of severe hypokalaemia. 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 poly-medicated, cirrhotic patients with oedema and ascites, coronary artery disease and cardiac failure patients.
In this latter situation, hypokalaemia 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. Hypokalaemia, as well as bradycardia, is then a pre-disposing 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 should be obtained during the first week following the start of treatment.
Detection of hypokalaemia requires its correction. Hypokalaemia found in association with low serum magnesium concentration can be refractory to treatment unless serum magnesium is corrected.
- Plasma magnesium:
Thiazides and related diuretics including indapamide have been shown to increase the urinary excretion of magnesium, which may result inhypomagnesaemia (see section 4.5 and 4.8).
- Plasma calcium:
Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transitory rise in plasma calcium. Frank hypercalcaemia 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 hypokalaemia.

• Uric acid:
Tendency to gout attacks may be increased in hyperuricaemic 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/ml, i.e. 220 μmol/L in an adult). In the elderly, this plasma creatinine must be adjusted in relation to age, weight and gender.
Hypovolaemia, 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 pre-existing renal insufficiency.

• Choroidal effusion, acute myopia and secondary angle-closure glaucoma: Sulfonamide or sulfonamide derivative drugs can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy
• Athletes:
The attention of athletes is drawn to the fact that this medicinal product contains an active ingredient, which may give a positive reaction in doping tests.

Effects on Driving

4.7 Effects on ability to drive and use machines
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.