Natrixam Special Precautions

Hypertensive crisis: The safety and efficacy of amlodipine in hypertensive crisis have not been established.
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. Hypokalemia may cause muscle disorders. Cases of Rhabdomyolysis have been reported, mainly in the context of severe hypokalemia. 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 previously. The first measurement of plasma potassium should be obtained during the first week following the start of treatment.
Detection of hypokalemia requires its correction. Hypokalemia 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 in hypomagnesaemia.
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Treatment should be withdrawn before the investigation of parathyroid function.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: Due to the presence of indapamide, monitoring of blood glucose is important in diabetics, in particular in the presence of hypokalemia.
Cardiac failure: Patients with heart failure should be treated with caution. In a long-term, placebo controlled study in patients with severe heart failure (NYHA class III and IV) the reported incidence of pulmonary edema was higher in the amlodipine treated group than in the placebo group. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Renal function: 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.
Amlodipine may be used in patients with renal failure at normal doses. Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine is not dialyzable.
The effect of the combination Indapamide + Amlodipine (Natrixam) has not been tested in renal dysfunction. In renal impairment, Indapamide + Amlodipine (Natrixam) doses should respect those of the individual components taken individually.
Uric acid: Due to the presence of indapamide, tendency to gout attacks may be increased in hyperuricemic patients.
Hepatic function: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose.
The effect of the combination Indapamide + Amlodipine (Natrixam) has not been tested in hepatic dysfunction. Taking into account the effect of indapamide and amlodipine, Indapamide + Amlodipine (Natrixam) is contraindicated in patients with severe hepatic impairment, and caution should be exercised in patients with mild to moderate hepatic impairment.
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: Athletes should note that this product contains an active substance which may cause a positive reaction in doping tests.
Excipients: Indapamide + Amlodipine (Natrixam) should not be administered to patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Level of sodium: Indapamide + Amlodipine (Natrixam) contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.
Driving and Using Machines: Indapamide + Amlodipine (Natrixam) has minor or moderate influence on the 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.
Amlodipine can have minor or moderate influence on the ability to drive and use machines. If patients taking amlodipine suffer from dizziness, headache, fatigue or nausea, the ability to react may be impaired. Caution is recommended especially at the start of treatment.
Use in the Elderly: Older patients can be treated with Indapamide + Amlodipine (Natrixam) according to renal function.