Product Details

Product Information of Natrixam

Contraindications

Hypersensitivity to the active substances, to other sulfonamides, to dihydropyridine derivatives or to any of the excipients listed in Description.
Severe renal failure (creatinine clearance below 30 ml/min).
Hepatic encephalopathy or severe impairment of liver function.
Hypokalaemia.
Severe hypotension.
Shock (including cardiogenic shock).
Obstruction of the outflow tract of the left ventricle (e.g., high grade aortic stenosis).
Haemodynamically unstable heart failure after acute myocardial infarction.

Special Precautions

Special warnings: Hepatic encephalopathy: When liver function is impaired, thiazide-related diuretics may cause, particularly in case of electrolyte imbalance, hepatic encephalopathy which can progress to hepatic coma. Due to the presence of indapamide, administration of Natrixam must be stopped immediately if this occurs.
Photosensitivity: Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics (see Adverse Reactions). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
Precaution for use: 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 (see Adverse Reactions and Overdosage).
Any diuretic treatment may cause hyponatraemia, sometimes with very serious consequences. Hyponatraemia with hypovolaemia 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 hypokalaemia 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 hypokalaemia (< 3.4 mmol/l) must be prevented in certain high risk populations, i.e. the elderly, malnourished and/or polymedicated, cirrhotic patients with oedema and ascites, coronary artery disease and cardiac failure patients. In this 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 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 as previously mentioned. The first measurement of plasma potassium should be obtained during the first week following the start of treatment.
Detection of hypokalaemia 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 hypercalcaemia may be due to previously unrecognised 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 hypokalaemia.
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 oedema 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.
Uric acid: Due to the presence of indapamide, tendency to gout attacks may be increased in hyperuricaemic patients.
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: Natrixam should not be administered to patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Level of sodium: Natrixam contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium-free’.
Effects on ability to drive and use machines: 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.
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.
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 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 dialysable.
The effect of the combination Natrixam has not been tested in renal dysfunction. In renal impairment, Natrixam doses should respect those of the individual components taken individually.
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 Natrixam has not been tested in hepatic dysfunction. Taking into account the effect of indapamide and amlodipine, Natrixam is contra-indicated in patients with severe hepatic impairment, and caution should be exercised in patients with mild to moderate hepatic impairment.
Use in the Elderly: Older patients can be treated with Natrixam according to renal function (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).

Use In Pregnancy & Lactation

Given the effects of the individual components in this combination product on pregnancy and lactation: Natrixam is not recommended during pregnancy.
Natrixam is not recommended during lactation.
Pregnancy: Linked to indapamide: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of indapamide in pregnant women. Prolonged exposure to thiazide during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause a foeto-placental ischaemia and growth retardation. Moreover, rare cases of hypoglycemia and thrombocytopenia in neonates have been reported following exposure near term.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Linked to amlodipine: The safety of amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Breastfeeding: Linked to indapamide: There is insufficient information on the excretion of indapamide/metabolites in human milk. Hypersensitivity to sulfonamide-derived medicines and hypokalaemia might occur. A risk to the newborns/infants cannot be excluded.
Indapamide is closely related to thiazide diuretics which have been associated, during breast-feeding, with a decrease or even suppression of milk lactation.
Linked to amlodipine: Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine on infants is unknown.
Fertility: Linked to indapamide: Reproductive toxicity studies showed no effect on fertility in female and male rats (see Pharmacology: Toxicology: Preclinical safety data under Actions). No effects on human fertility are anticipated.
Linked to amlodipine: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse reactions were found on male fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).