Natrixam Uses, Dosage, Side Effects, Precautions & Warnings

Generic  drug of the Therapeutic class: Cardiology and angiology
Active ingredients: Indapamide , Amlodipine

what is Natrixam medication used for and indication?

NATRIXAM is indicated for the treatment of essential hypertension, as a replacement therapy, in patients already controlled with indapamide and amlodipine taken simultaneously at the same dose.

Natrixam  Dosage

Dosage

• One tablet per day in one take, preferably in the morning. The tablet should be swallowed whole with water and should not be chewed.
• The fixed combination is not suitable for the initiation of treatment.
• If a change in dosage is required, dosage adjustment should be made with each substance taken separately.

Special populations

Pediatric population

• The safety and efficacy of NATRIXAM have not been established in children and adolescents.
• No data is available.

Patients with renal insufficiency (see sections Contraindications and Warnings and precautions for use)

• In severe renal impairment (creatinine clearance less than 30 ml / min), treatment is contraindicated.
• In patients with mild to moderate renal impairment, no dosage adjustment is necessary.

Elderly (see sections Warnings and precautions for use and Pharmacokinetic properties)

• Elderly patients may be treated with NATRIXAM depending on their renal function.

Patients with hepatic insufficiency (see sections Contraindications and Warnings and precautions for use)

• In severe hepatic impairment, treatment is contraindicated.
• The recommended dosages of amlodipine have not been established in patients with mild to moderate hepatic impairment, therefore the dose should be chosen with caution and treatment should be initiated at the lowest dose . use and Pharmacokinetic properties).

Mode d’administration

• Oral route.

Natrixam Contraindications

• Hypersensitivity to the active substances, to other sulfonamides, to dihydropyridine derivatives or to any of the excipients listed in the Composition section .
• Severe renal impairment (creatine clearance less than 30 ml / min).
  • Hepatic encephalopathy or severe hepatic impairment.
  • Hypokalaemia.
  • Feeding with milk.
• Severe hypotension.
• State of shock (including cardiogenic shock).
• Obstacle of the ejection path of the left ventricle (eg: high degree aortic stenosis).
• Hemodynamically unstable heart failure after acute myocardial infarction.

How To Take Natrixam?

• Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if in doubt.
• The recommended dose is one tablet once a day, preferably in the morning.
• The tablet should be swallowed whole with water and should not be chewed.

how does Natrixam work?

Pharmacotherapeutic group: Calcium channel blockers and diuretics, ATC code: C08GA02

Action mechanism

• Indapamide is an indol-ringed sulfonamide derivative, pharmacologically related to 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 extent, the excretion of potassium and magnesium, thus increasing diuresis and exerting an antihypertensive action.
• Amlodipine is a calcium ion flux inhibitor belonging to the dihydropyridine family (slow channel inhibitor or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into heart muscle and vascular smooth muscle.
• The mechanism of the antihypertensive action is linked to a direct relaxing effect at the level of vascular smooth muscle.

Pharmacodynamic effects

• Phase II and III studies have shown an antihypertensive effect lasting 24 hours for indapamide monotherapy. It appears at doses at which its diuretic properties are weak.
• Its antihypertensive activity is related to an improvement in arterial compliance and a decrease in total peripheral and arteriolar resistance.
• Indapamide reduces left ventricular hypertrophy.
• There is a plateau in the antihypertensive effect of thiazide and related diuretics beyond a certain dose, while the side effects continue to increase: if the treatment is ineffective, do not seek to increase the doses.
• In addition, in the short, medium and long term in hypertension, it has been shown that indapamide:
  • Complies with lipid metabolism: triglycerides, LDL cholesterol and HDL cholesterol,
  • Respects the carbohydrate metabolism, even in hypertensive diabetics.
• In hypertensive patients, a daily intake of amlodipine provides a clinically significant reduction in blood pressure, while lying or standing for 24 hours. The progressive action of amlodipine makes it possible to avoid attacks of hypotension.
• Amlodipine does not cause undesirable metabolic effects or alter plasma lipid levels, making it suitable for use in patients with asthma, diabetes or gout.

Clinical efficacy and safety

• The effect of NATRIXAM on morbidity and mortality has not been established.
• Regarding amlodipine, a randomized double-blind morbidity-mortality study called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was carried out to compare the effects of new substances: amlodipine 2.5-10 mg / day (calcium channel blocker) or lisinopril 10-40 mg / day (ACE inhibitor) as first-line therapy, with a thiazide diuretic, chlorthalidone 12.5-25 mg / day, in patients with mild to moderate arterial hypertension.
• A total of 33,357 hypertensive patients aged 55 or over were randomized and followed for an average of 4.9 years. Patients had at least one risk factor for additional coronary artery disease including a history of myocardial infarction or stroke> 6 months or other atherosclerotic-related cardiovascular disease (51.5% total), type 2 diabetes (36.1%), HDL-C <35 mg / dl (11.6%), left ventricular hypertrophy diagnosed by electrocardiogram or echocardiography (20.9%), smoking (21.9%) %).
• The primary endpoint was a component of coronary death or non-fatal myocardial infarction.
• The study did not show a significant difference on the primary endpoint between the amlodipine group and the chlorthalidone group: RR 0.98 (95% CI (0.90-1.07) p = 0.65). Among the secondary endpoints, the incidence of heart failure (component of a combined cardiovascular composite endpoint) was significantly higher in the amlodipine group, compared to the chlorthalidone group (10.2% vs 7.7%, RR 1, 38, (95% CI [1.25-1.52] p <0.001)). However, no significant difference was shown in all-cause mortality between the amlodipine group and the chlorthalidone group, RR 0.96 (95% CI [0.89-1.02] p = 0.20).

Pediatric population

• There are no data available from the use of NATRIXAM in children.
• The European Medicines Agency has granted an exemption from the obligation to submit the results of studies with NATRIXAM in all subgroups of the pediatric population {in accordance with the decision of the Pediatric Investigation Plan, in the indication authorized} (see section Dosage and method of administration for information on pediatric use).

How To Store Natrixam?

• Keep this medication out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton. The expiration date refers to the last day of that month.
• Store at a temperature not exceeding 30 ° C.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away the medicines you no longer use. These measures will help protect the environment.

side effects of natrixam

Summary of the safety profile

• The most common side effects reported with indapamide and amlodipine when administered separately are drowsiness, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle edema, edema and pain. tiredness.

List of side effects

• The following side effects have been observed and reported during treatment with indapamide and amlodipine with the following frequencies: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1 / 1,000 to <1/100); rare (≥ 1 / 10,000 to <1 / 1,000); very rare (<1 / 10,000); unknown (cannot be estimated from the available data).

MedDRA System organ	Side effects	Frequency
		Indapamide	Amlodipine
Blood and lymphatic system disorders	Leukocytopenia	Very rare	Very rare
	Thrombocytopenia	Very rare	Very rare
	Agranulocytosis	Very rare	–
	Aplastic anemia	Very rare	–
	Hemolytic anemia	Very rare	–
Immune system disorders	Allergic reactions	–	Very rare
Metabolism and nutrition disorders	Hypokalaemia	Frequent During clinical studies, hypokalaemia (serum potassium <3.4 mmol / L) was observed in 10% of patients, it was <3.2 mmol / L in 4% of patients after 4 to 6 weeks of treatment. After 12 weeks of treatment, the mean decrease in serum potassium was 0.23 mmol / l. (see section Warnings and precautions for use )	–
	Hyperglycemia	–	Very rare
	Hypercalcemia	Very rare	–
	Hyponatremia with hypovolaemia *	Unknown	–
Psychiatric disorders	Insomnia	–	Rare
	Mood swings (including anxiety)	–	Rare
	Depression	–	Rare
	Confusion	–	Rare
Nervous system disorders	Drowsiness	–	Common (especially at the start of treatment)
	Dizziness	–	Common (especially at the start of treatment)
	Headache	Rare	Common (especially at the start of treatment)
	Tremors	–	Rare
	Dysgeusia	–	Rare
	Syncope	Unknown	Rare
	Hypoaesthesia	–	Rare
	Paresthesia	Rare	Rare
	Dizziness	Rare	–
	Hypertonia	–	Very rare
	Peripheral neuropathy	–	Very rare
Eye disorders	Vision disturbances (including diplopia)	–	Rare
Ear and labyrinth disorders	Tinnitus	–	Rare
Cardiac disorders	Palpitations	–	Frequent
	Myocardial infarction	–	Very rare
	Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation)	Very rare	Very rare
	Torsade de pointes (potentially fatal)	Unknown (see section 4.4 and Interactions with other medicinal products and other forms of interactions )	–
Vascular disorders	Flush	–	Frequent
	Hypotension	Very rare	Rare
	Vasculitis	–	Very rare
Respiratory, thoracic and mediastinal disorders	Dyspnea	–	Rare
	Rhinitis	–	Rare
	Cough	–	Very rare
Gastrointestinal disorders	Abdominal pain	–	Frequent
	Nausea	Rare	Frequent
	Vomiting	Rare	Rare
	Dyspepsia	–	Rare
	Bowel movement disorders (including diarrhea and constipation)	–	Rare
	Dry mouth	Rare	Rare
	Pancreatitis	Very rare	Very rare
	Gastritis	–	Very rare
	Gingival hyperplasia	–	Very rare
	Constipation	Rare	Rare
Hepato-biliary disorders	Hepatitis	Unknown	Very rare
	Jaundice	–	Very rare
	Elevation of liver enzymes	Unknown	Very rare**
	Impaired liver function	Very rare	–
	Possibility of hepatic encephalopathy in case of hepatic insufficiency	Unknown (see sections Contraindications and Warnings and precautions for use )	–
Skin and subcutaneous tissue disorders	Maculopapular rashes	Frequent	–
	Purpura	Rare	Rare
	Alopecia	–	Rare
	Skin discoloration	–	Rare
	Hyperhidrosis	–	Rare
	Pruritus	–	Rare
	Rash	–	Rare
	Exanthema	–	Rare
	Angioedema	Very rare	Very rare
	Urticaria	Very rare	Very rare
	Toxic epidermal necrolysis	Very rare	–
	Stevens-Johnson syndrome	Very rare	Very rare
	Erythema multiforme	–	Very rare
	Exfoliating dermatitis	–	Very rare
	Angioedema	–	Very rare
	Photosensitivity	Cases of photosensitivity reactions have been reported (see section Warnings and precautions for use )	Very rare
	Possible worsening of pre-existing systemic lupus erythematosus	Unknown	–
Musculoskeletal, and connective tissue disorders	Ankle edema	–	Frequent
	Arthralgia	–	Rare
	Myalgia	–	Rare
	Muscle cramps	–	Rare
	Back pain	–	Rare
Kidney and urinary tract disorders	Urination disorders	–	Rare
	Nocturia	–	Rare
	Increased urinary frequency	–	Rare
	Renal failure	Very rare	–
Reproductive system and breast disorders	Incapacity	–	Rare
	Gynecomastia	–	Rare
General disorders and administration site conditions	Edemas	–	Frequent
	Tired	Rare	Frequent
	Chest pain	–	Rare
	Asthenia	–	Rare
	Pain	–	Rare
	Discomfort	–	Rare
Investigations	Increased weight	–	Rare
	Decrease in weight	–	Rare
	Prolongation of the QT interval on the electrocardiogram	Unknown (see sections 4.4 and Interactions with other medicinal products and other forms of interaction )	–
	Elevation of blood glucose and uric acid during treatment	Unknown The use of these diuretics should be carefully measured in patients with gout or diabetes.	–

* responsible for dehydration and orthostatic hypotension. The concomitant loss of chloride ions may secondarily lead to compensatory metabolic alkalosis: the incidence and magnitude of this effect are low.

** generally suggesting cholestasis

• Exceptional cases of extrapyramidal syndrome have been reported with amlodipine.

Natrixam Interactions

RELATED TO INDAPAMIDE

Not recommended associations

Lithium

• Increased blood lithium with signs of overdose, such as during a deodorant diet (decrease in urinary excretion of lithium). However, if the use of diuretics is necessary, careful monitoring of serum lithium levels and adjustment of the dosage are required.

Combinations subject to precautions for use

Medicines that can induce torsades de pointes

• Antiarythmiques de classe Ia (quinidine, hydroquinidine, disopyramide).
• Antiarythmiques de classe III (amiodarone, sotalol, dofetilide, ibutilide).

Some antipsychotics:

• • Phénothiazines (chlorpromazine, cyamémazine, lévomépromazine, thioridazine, trifluopérazine).
  • Benzamides (amisulpiride, sulpiride, sultopride, tiapride).
  • Butyrophenones (droperidol, haloperidol).
• Autres : bépridil, cisapride, diphemanil, érythromycine IV, halofantrine, mizolastine, pentamidine, sparfloxacine, moxifloxacine, vincamine IV.
• Increased risk of ventricular arrhythmia, especially torsades de pointes (hypokalaemia is a risk factor).
• Hypokalaemia should be monitored and corrected if necessary, before introducing this combination. The clinical condition, plasma electrolytes and ECG should be monitored.
• Use substances that do not present a risk of torsades de pointes in the presence of hypokalaemia.

NSAIDs (systemically), including selective inhibitors of COX-2, salicylates at high doses (≥ 3 g / day) 

• Possible decrease in the antihypertensive effect of indapamide.
• Risk of acute renal failure in dehydrated patients (decrease in glomerular filtration). Hydrate the patient; Look at the kidney function at the start of the treatment.

 Angiotensin converting enzyme (ACE)

• Risk of sudden arterial hypotension and / or acute renal failure when initiating treatment with an ACE inhibitor in the event of pre-existing sodium depletion (especially in subjects with stenosis of the renal artery).
• In essential hypertension, when prior diuretic treatment may have resulted in sodium depletion, it is necessary:
  • either stop the diuretic 3 days before the start of treatment with the IEC and then reintroduce a hypokalaemic diuretic if necessary,
  • or administer low initial doses of the IEC and increase gradually.
• In congestive heart failure, start with a very low dose of ACEI possibly after reducing the dose of the associated hypokalaemic diuretic.

In all cases, monitor renal function (serum creatinine level) during the first weeks of treatment with ACE

Other hypokalaemia: amphotericin B (IV), gluco- and mineralocorticoid (systemically) tetracosactide, stimulant laxatives

• Increased risk of hypokalaemia (additive effect).
• Monitoring of serum potassium and, if necessary, correction; to be particularly taken into account in the event of concomitant digitalis therapy. Use non-stimulant laxatives.

Digitaliques

• Hypokalaemia promotes the toxic effects of digitalis.
• Monitoring of serum potassium, ECG and, if necessary, adapt the treatment.

Baclofen

• Increase in the antihypertensive effect.
• Hydrate the patient, monitor renal function at the start of treatment.

Allopurinol

• Combination with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.

Associations to take into account

Potassium sparing diuretics (amiloride, spironolactone, triamterene)

• In the case of a rational combination, useful for certain patients, the occurrence of hypokalaemia or hyperkalaemia (in particular in patients with renal insufficiency or diabetes) cannot be excluded. Serum potassium and ECG should be monitored and, if necessary, reconsider treatment.

Metformin

• Increased risk of occurrence of lactic acidosis due to metformin triggered by a possible functional renal failure linked to the association with diuretics and more especially with loop diuretics.
• Do not use metformin when serum creatinine exceeds 15 mg / l (135 µmoles / l) in men and 12 mg / l (110 µmoles / l) in women.

Iodine Contrast Media

• In the event of dehydration caused by diuretics, there is an increased risk of acute renal failure, in particular when using large doses of iodinated contrast agents.
• Rehydration before administration of the iodized product.

Antidepressants imipramine (tricyclic), neuroleptics

• Antihypertensive effect and increased risk of orthostatic hypotension (additive effect).

Calcium (salts)

• Risk of hypercalcemia by decreased urinary elimination of calcium.

Ciclosporine, Tacrolimus

• Risk of increased serum creatinine without modification of circulating levels of ciclosporin, even in the absence of water and sodium depletion.

Corticosteroids, tetracosactide (systemic)

• Decreased antihypertensive effect (hydrosodium retention of corticosteroids).

RELATED TO AMLODIPINE

• Dantrolene (infusion) : In animals, cases of ventricular fibrillation and lethal cardiovascular collapse have been observed in association with hyperkalaemia following IV administration of verapamil and dantrolene. In view of the risk of hyperkalaemia, it is recommended to avoid the concomitant administration of calcium channel blockers such as amlodipine in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
• Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients, which may lead to increased hypotensive effects.
• CYP3A4 inhibitors : Concomitant use of amlodipine with strong or moderate inhibitors of CYP3A4 (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may cause a significant increase in the plasma concentration of amlodipine. The clinical translation of these pharmacokinetic variations may be more pronounced in the elderly. Therefore, clinical monitoring and dose adjustment may be required.
• The risk of hypotension is increased in patients receiving simultaneous clarithromycin and amlodipine. Close monitoring of patients is recommended when amlodipine is combined with clarythromycin.
• CYP3A4 inducers: No data are available on the effect of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (eg, rifampicin, St. John’s Wort [Hypericum perforatum]) may result in decreased plasma concentration of amlodipine. Amlodipine should be used with caution in combination with inducers of the CYP3A4 isoenzyme.

Effects of Amlodipine on Other Medicines:

• • The hypotensive effects of amlodipine are in addition to those of other drugs with antihypertensive properties.
  • In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.
  • Tacrolimus: There is a risk of increased plasma concentrations of tacrolimus when co-administered with amlodipine. In order to avoid tacrolimus toxicity, administration of amlodipine to a patient treated with tacrolimus requires monitoring of tacrolimus plasma concentrations and dose adjustment of tacrolimus if necessary.
  • Ciclosporin: No interaction studies have been performed with ciclosporin and amlodipine in healthy volunteers or other populations, except in patients who have undergone kidney transplantation; a variable increase in the minimum concentration of ciclosporin was then observed (from 0% to 40% on average). Cyclosporin levels should be monitored in renal transplant recipients treated with amlodipine and a reduction in the dose of cyclosporin should be considered if necessary.
  • Simvastatin  : Co-administration of repeated doses of 10 mg amlodipine and 80 mg of simvastatin resulted in an increase in exposure to simvastatin by 77% compared to administration of simvastatin alone. Limit the dose of simvastatin to 20 mg per day in patients taking amlodipine.

• Not applicable.

Drive and use machines

• NATRIXAM may affect your ability to drive and use machines.
• If after treatment you do not feel well, have a dizzy spell, feel tired, or have a headache, you should not drive or use machines and should contact your doctor. doctor immediately.
• If this happens, you should avoid driving or any other activity that requires alertness.

Warnings and Precautions

Special warnings

Hepatic encephalopathy:

• In the event of hepatic impairment, thiazide-like diuretics may induce hepatic encephalopathy, particularly in the event of electrolyte imbalance. In this case, due to the presence of indapamide, the administration of NATRIXAM should be stopped immediately.

Photosensitivity:

• Photosensitivity has been reported with thiazide and related diuretics (see section 4.8). If a photosensitivity reaction occurs during treatment, it is recommended to stop treatment. If a new administration of the diuretic becomes necessary, it is recommended to protect the parts of the body exposed to the sun or to artificial UVA rays.

Precautions for use

Patients with hypertensive crisis:

• The safety and efficacy of amlodipine in hypertensive crisis have not been established.

Hydro-electrolyte balance:

 Sodium

• It should be checked before starting treatment and at regular intervals thereafter. Since the drop in serum sodium may initially be asymptomatic, regular monitoring is therefore essential and should be even more frequent in the elderly and patients with cirrhosis (see sections Undesirable effects and Overdose).
• Any diuretic treatment can indeed cause hyponatremia, sometimes with serious consequences. Hyponatremia associated with hypovolaemia may be responsible for dehydration and orthostatic hypotension. The concomitant loss of chloride ions may lead to secondary compensatory metabolic alkalosis: the incidence and degree of this effect is low.

Potassium

• Potassium depletion with hypokalaemia constitutes the major risk of thiazide and related diuretics. The risk of occurrence of hypokalaemia (<3.4 mmol / l) must be prevented in certain high-risk populations represented by the elderly, the undernourished and / or drug-medicated, cirrhotics with edema and ascites, coronary patients and heart failure. Indeed, in this case, hypokalaemia increases the cardiac toxicity of digitalis and the risk of arrhythmias.
• People with a long QT interval are also at risk, whether the origin is congenital or iatrogenic. Hypokalaemia, as well as bradycardia, then acts as a factor favoring the onset of severe arrhythmias, in particular torsades de pointes, which is potentially fatal.
• In all these cases, more frequent checks of the serum potassium are necessary. The first serum potassium check should be carried out during the 1st week following the start of treatment.
• The finding of hypokalaemia requires its correction.

Serum Calcium

• Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transient increase in serum calcium. Frank hypercalcemia may be related to unrecognized hyperparathyroidism. Interrupt treatment before exploring parathyroid function.

Blood sugar:

• Due to the presence of indapamide, it is important to control blood sugar in diabetics, especially in the presence of hypokalaemia.

Patients with heart failure:

• Patients with heart failure should be treated with caution. In a long-term placebo-controlled study in patients with severe heart failure (NYHA classes III and IV) the reported incidence of pulmonary edema was higher in the group treated with amlodipine compared to the placebo group.
• Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, because they may increase the risk of cardiovascular events and mortality.

Kidney function:

• Thiazide and related diuretics are only fully effective when renal function is normal or only slightly altered (serum creatinine below values ​​of the order of 25 mg / l, ie 220 µmol / l for an adult). In the elderly, the serum creatinine value must be readjusted according to the age, weight and sex of the patient.
• Hypovolaemia, secondary to the loss of water and sodium induced by the diuretic at the start of treatment, leads to a reduction in glomerular filtration. This can lead to an increase in blood urea and serum creatinine. This transient functional renal failure is of no consequence in subjects with normal renal function but may aggravate a pre-existing renal failure.
• Amlodipine can be used in patients with renal impairment at normal doses. Changes in amlodipine plasma concentrations do not correlate with the degree of renal impairment. Amlodipine is not dialyzable.
• The effect of NATRIXAM combination has not been tested in patients with renal impairment. In renal impairment, the doses of NATRIXAM should be the same as for each substance taken separately.

Uric acid :

• Due to the presence of indapamide, the tendency to gout attacks may be increased in hyperuricaemic patients.

Liver function:

• The half-life of amlodipine is increased and its AUC (Area Under the Curve) is greater in patients with hepatic impairment. Dosage recommendations have not been established, therefore, amlodipine should be initiated at the lowest effective dose and with caution, both during initiation of therapy and during dose escalation.
• The effect of NATRIXAM combination has not been tested in patients with hepatic impairment. Due to the effect of indapamide and amlodipine, NATRIXAM is contraindicated in patients with severe hepatic impairment, and caution should be taken in patients with mild to moderate hepatic impairment.

Elderly patients:

• Elderly patients may be treated with NATRIXAM depending on their renal function (Pharmacokinetics).

Excipients :

• This medicine contains lactose. Its use is not recommended in patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases).

PREGNANCY & BREAST-FEEDING & FERTILITY

Taking into account the respective effects of each of the two substances present in the combination on pregnancy and lactation:

• Natrixam is not recommended during pregnancy.
• Natrixam is contraindicated during breast-feeding.

Pregnancy 

Linked to indapamide:

• There are no data or there are limited data (less than 300 pregnancies) from the use of indapamide in pregnant women. Prolonged exposure to thiazide diuretics at the 3 ^th trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow. This can result in fetal ischemia and intrauterine growth retardation.
• In addition, rare cases of hypoglycaemia and thrombocytopenia in newborns have been reported during near term exposures.
• Studies in animals have not produced any direct or indirect harmful effects on reproduction ( see Preclinical safety ).

Linked to amlodipine:

• In women, the safety of amlodipine during pregnancy has not been established.
• In animal studies, reprotoxicity has been observed at high doses ( see Preclinical Safety ).

Feeding with milk

Linked to indapamide:

• There are insufficient data on the excretion of indapamide / metabolites in human milk.
• Hypersensitivity to sulfonamide derivatives and hypokalaemia may occur. A risk to newborns / infants cannot be excluded.
• Indapamide is closely linked to thiazide diuretics which have been associated with breastfeeding, in the reduction or even the cessation of lactation.

Linked to amlodipine:

• Amlodipine is excreted in breast milk. The proportion of the maternal dose received by the infant has been estimated at an interquartile range of 3-7%, with a maximum of 15%. The effect of amlodipine on the infant is unknown.

Fertility

Linked to indapamide:

• Reproductive toxicity studies in male and female rats did not show any effect on fertility ( see Preclinical Safety ). No effect on fertility is expected in humans.

Linked to amlodipine:

• Reversible biochemical changes in the sperm head have been reported in some patients treated with calcium channel blockers. There is insufficient clinical data regarding the potential effect of amlodipine on fertility. In a study carried out in rats, adverse effects were detected on male fertility ( see Preclinical safety ).

What happens if I overdose from Natrixam?

• Immediately consult your doctor or pharmacist.
• Taking too many tablets can sometimes lead to a dangerous drop in your blood pressure. You may feel dizzy, drowsy, pass out, or feel faint. You may be prone to nausea, vomiting, muscle cramps, confusion, and changes in the amount of urine produced by the kidneys. If the blood pressure drops too severely, shock may occur. Your skin may become cold and clammy and you may lose consciousness.

What should I do if I miss a dose?

• Do not worry. If you forget to take a tablet, take the next dose at your normal pace.
• Do not take a double dose to make up for the dose you forgot to take.

What happens if you stop taking Natrixam ?

• As the treatment of high blood pressure is usually a long-term treatment, you should seek advice from your doctor before stopping it.
• If you have further questions on the use of this medicine, ask your doctor or pharmacist for more information.

What is  Forms and Composition ?

SHAPES and PRESENTATIONS

1.5 mg / 5 mg modified release film-coated tablet (round, bilayer, 9 mm in diameter, with the Servier logo debossed on one side; white) and 1.5 mg / 10 mg (round, bilayer, 9 mm in diameter, with the Servier logo engraved on one side; pink):   Boxes of 30 and 90, in a blister pack.

natrixam composition 

	p cp of
	1.5 mg / 5 mg	1.5 mg / 10 mg
Indapamide (INN)	1.5 mg	1.5 mg
Amlodipine (INN)	5 mg	10 mg
(amlodipine as besilate: 6.935 mg / tab to 1.5 mg / 5 mg; 13.87 mg / tab to 1.5 mg / 10 mg)

• Excipients: Core: hypromellose E464, lactose monohydrate, magnesium stearate E572, povidone E1201, colloidal anhydrous silica, calcium hydrogen phosphate dihydrate, microcrystalline cellulose E460, croscarmellose sodium E468, pregelatinized corn starch. Film-coating: glycerol E422, hypromellose E464, macrogol 6000, magnesium stearate E572, titanium dioxide E171; iron oxide red E172 (tab 1.5 mg / 10 mg).
• Excipient with known effect: lactose monohydrate (104.5 mg / tab).

NOT’s

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general information:

• Includes a general description of the drug, its use, brand names, FAQs, and relevant news and articles

Additional information:

• General explanation about dealing with the medicine: how to take the medicine, the doses and times of it, the start and duration of its effectiveness, the recommended diet during the period of taking the medicine, the method of storage and storage, recommendations in cases for forgetting the dose and instructions to stop taking the drug and take additional doses.

Special warnings:

• For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

• It treats possible side effects and drug interactions that require attention and its effect on continuous use.
• The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.

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