Natrilix sr инструкция по применению

Топ 20 лекарств с такими-же компонентами:

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Акрипамид^®

Таблетки, покрытые пленочной оболочкой, круглые, двояковыпуклые, белого или белого с кремоватым или сероватым оттенком цвета. Допускается наличие шероховатости.

Акрипамид^® ретард

Таблетки, покрытые пленочной оболочкой, круглые, двояковыпуклые, белого или белого с кремоватым или сероватым оттенком цвета.

Гиперчувствительность к индапамиду, другим производным сульфонамида или другим компонентам препарата, декомпенсация функции почек (анурия) и/или печени (в т.ч. с энцефалопатией), гипокалиемия, одновременный прием препаратов, удлиняющих интервал QT, беременность, период лактации, пациентам с непереносимостью лактозы, галактоземией, синдромом нарушения всасывания глюкозы/галактозы, возраст до 18 лет (эффективность и безопасность не установлены).

С осторожностью: сахарный диабет в стадии декомпенсации, гиперурикемия (особенно сопровождающаяся подагрой и уратным нефролитиазом), нарушения функции печени и/или почек, нарушение водно-электролитного баланса, гиперпаратиреоз, больным с увеличенным интервалом QT на ЭКГ, в т.ч. получающим сочетанную терапию.

Беременность

Как правило, в период беременности не следует назначать диуретические препараты. Нельзя использовать эти препараты для лечения физиологических отеков при беременности. Диуретические препараты могут вызывать фетоплацентарную ишемию и приводить к нарушению развития плода.

Период кормления грудью

Не рекомендуется назначать Арифон^® ретард кормящим матерям (индапамид выделяется с грудным молоком).

Со стороны ЖКТ: запор или диарея, чувство дискомфорта в области живота, тошнота, рвота, анорексия, сухость во рту; возможно развитие печеночной энцефалопатии; редко — панкреатит.

Со стороны нервной системы: астения, головокружение, вертиго, нервозность, головная боль, сонливость, повышенная утомляемость, общая слабость, недомогание, бессонница, депрессия, спазм мышц, напряженность, раздражительность, тревога, парестезии.

Со стороны органов чувств: конъюнктивит, нарушение зрения.

Со стороны дыхательной системы: ринит, кашель, фарингит, синусит.

Со стороны сердечно-сосудистой системы: ортостатическая гипотензия, аритмия, сердцебиение, изменения ЭКГ, характерные для гипокалиемии.

Со стороны мочевыделительной системы: никтурия, полиурия, увеличение частоты развития инфекций.

Аллергические реакции: кожная сыпь, крапивница, зуд, геморрагический васкулит.

Лабораторные показатели: гиперурикемия, гипергликемия, глюкозурия, гипокалиемия, гипонатриемия, гипохлоремический алкалоз, повышение азота мочевины в плазме крови, гиперкреатининемия, гиперкальциемия.

Очень редко — тромбоцитопения, лейкопения, агранулоцитоз, аплазия костного мозга и гемолитическая анемия.

Прочие: гриппоподобный синдром, боль в грудной клетке, боль в спине, снижение либидо и потенции, ринорея, потливость, снижение массы тела, обострение течения системной красной волчанки.

Симптомы: тошнота, рвота, слабость, нарушение функции ЖКТ, водно-электролитные нарушения, артериальная гипотензия, головокружение, сонливость, спутанность сознания, угнетение дыхания; у пациентов с нарушением функции печени (циррозом печени) возможно развитие печеночной комы.

Лечение: промывание желудка и/или назначение активированного угля, коррекция водно-электролитного баланса, симптоматическая терапия. Специфического антидота нет.

Гипотензивное средство, тиазидоподобный диуретик с умеренным по силе и длительным действием, производное бензамидов. Снижает тонус гладкой мускулатуры артерий, уменьшает ОПСС. Обладает умеренным салуретическим и диуретическим эффектами, которые связаны с блокадой реабсорбции ионов натрия, хлора, водорода, и, в меньшей степени, ионов калия в проксимальных канальцах и кортикальном сегменте дистального канальца нефрона. Сосудорасширяющие эффекты и снижение ОПСС обусловлены следующими механизмами: снижением реактивности сосудистой стенки к норадреналину и ангиотензину II; повышением синтеза ПГ, обладающих сосудорасширяющей активностью; угнетением тока кальция в гладкомышечных клетках сосудов. Способствует уменьшению гипертрофии левого желудочка сердца. В терапевтических дозах не влияет на липидный и углеводный обмены (в т.ч. у больных с сопутствующим сахарным диабетом).

Антигипертензивный эффект развивается в конце первой/начале второй недели при постоянном приеме препарата и сохраняется в течение 24 ч на фоне однократного приема.

После приема внутрь быстро и полностью всасывается из ЖКТ. Биодоступность — высокая (93%). Прием пищи несколько замедляет скорость, но не влияет на полноту абсорбции. C_max в крови Акрипамида^® достигается через 1–2 ч. C_max в плазме крови Акрипамида^® ретард достигается через 12 ч после приема внутрь; при повторных приемах колебания концентрации препарата в плазме крови в интервале между приемами двух доз уменьшаются.

Равновесная концентрация достигается через 7 дней регулярного приема. На 70–80% связывается с белками плазмы крови. Связывается также с эластином гладких мышц сосудистой стенки. Имеет высокий объем распределения, проходит через гистогематические (в т.ч. плацентарный) барьеры, проникает в грудное молоко. Метаболизируется в печени. T_1/2 индапамида составляет в среднем 14–18 ч. Выводится из организма почками (до 80%) преимущественно в виде метаболитов (в неизмененном виде выводится около 5%), через кишечник — 20%. У больных с почечной недостаточностью фармакокинетика не меняется. Не кумулирует.

• Диуретическое средство [Диуретики]

При одновременном применении индапамида с препаратами лития возможно повышение концентрации лития в плазме крови (снижение выведения с мочой), литий оказывает нефротоксическое действие.

Астемизол, эритромицин (при в/в введении), пентамидин, сультоприд, терфенадин, винкамин, антиаритмические препараты IА класса (хинидин, дизопирамид) и III класса (амиодарон, бретилиум, соталол) повышают вероятность возникновения нарушений сердечного ритма типа torsades de pointes (желудочковая тахикардия типа «пируэт»).

НПВС, ГКС, тетракозактид, симпатомиметики снижают гипотензивное действие, баклофен — увеличивает.

Салуретики, сердечные гликозиды, глюко- и минералокортикоиды, тетракозактид, амфотерицин В (при в/в введении), слабительные средства — повышают риск развития гипокалиемии.

При одновременном применении с сердечными гликозидами повышается вероятность развития дигиталисной интоксикации, с препаратами кальция — гиперкальциемии, с метформином — возможно усугубление молочно-кислого ацидоза.

Комбинация с калийсберегающими диуретиками может быть эффективна у некоторой категории больных, при этом, однако, полностью не исключается вероятность развития гипо- или гиперкалиемии, особенно у больных с сахарным диабетом и почечной недостаточностью.

Ингибиторы АПФ увеличивают риск развития артериальной гипотензии и/или острой почечной недостаточности (особенно при имеющемся стенозе почечной артерии).

Контрастные йодсодержащие средства в высоких дозах увеличивают риск развития нарушений функции почек (обезвоживание организма). Перед применением контрастных йодсодержащих средств больным необходимо восстановить потерю жидкости.

Трициклические антидепрессанты и антипсихотические препараты усиливают гипотензивное действие и увеличивают риск развития ортостатической гипотензии.

Циклоспорин повышает риск развития гиперкреатининемии.

Снижает эффект непрямых антикоагулянтов (производных кумарина или индандиона) вследствие повышения концентрации факторов свертывания в результате уменьшения объема циркулирующей крови и повышения их продукции печенью (может потребоваться коррекция дозы).

Усиливает блокаду нервно-мышечной передачи, развивающуюся под действием недеполяризующих миорелаксантов.

В сухом, защищенном от света месте, при температуре не выше 25 °C.

Хранить в недоступном для детей месте.

Срок годности препарата Акрипамид^®

таблетки пролонгированного действия, покрытые пленочной оболочкой 1.5 мг — 2 года.

таблетки, покрытые пленочной оболочкой 2.5 мг — 4 года.

Не применять по истечении срока годности, указанного на упаковке.

Акрипамид^®

в контурной ячейковой упаковке 10 шт; в пачке картонной 1, 2, или 3 упаковки.

Акрипамид^® ретард

в упаковке контурной ячейковой 10 шт.; в пачке картонной 3 или 6 упаковок

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One prolonged-release film-coated tablet contains 1.5 mg indapamide.

Excipient with known effect: 124.5 mg lactose monohydrate

Prolonged-release tablet.

White, round, film-coated tablet.

Posology

One tablet per 24 hours, preferably in the morning, to be swallowed whole with water and not chewed.

At higher doses the antihypertensive action of indapamide is not enhanced but the saluretic effect is increased.

Special populations

Renal impairment :

In severe renal failure (creatinine clearance below 30 ml/min), treatment is contraindicated.

Thiazide and related diuretics are fully effective only when renal function is normal or only minimally impaired.

Hepatic impairment :

In severe hepatic impairment, treatment is contraindicated.

Elderly :

In the elderly, the plasma creatinine must be adjusted in relation to age, weight and gender. Elderly patients can be treated with Natrilix SR when renal function is normal or only minimally impaired.

Paediatric population:

The safety and efficacy of Natrilix SR in children and adolescents have not been established. No data are available.

Method of administration

Oral use

—

— Severe renal failure.

— Hepatic encephalopathy or severe impairment of liver function.

— Hypokalaemia.

Special warnings

When liver function is impaired, thiazide-related diuretics may cause hepatic encephalopathy, particularly in case of electrolyte imbalance. Administration of the diuretic must be stopped immediately if this occurs.

Photosensitivity:

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics. 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.

Excipients:

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Special precautions for use

— 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 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. 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 above. 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:

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/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.

— Athletes:

The attention of athletes is drawn to the fact that this medicinal product contains a drug substance, which may give a positive reaction in doping tests.

Combinations that are not recommended:

Lithium:

Increased plasma lithium with signs of overdosage, as with a salt-free diet (decreased urinary lithium excretion). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dose adjustment are required.

Combinations requiring precautions for use:

Torsades de pointes-inducing drugs:

— class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide),

— class III antiarrhythmics (amiodarone, sotalol, dofetilide, ibutilide),

— some antipsychotics :

phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine),

benzamides (amisulpride, sulpiride, sultopride, tiapride)

butyrophenones (droperidol, haloperidol)

others: bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV.

Increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalaemia is a risk factor).

Monitor for hypokalaemia and correct, if required, before introducing this combination. Clinical, plasma electrolytes and ECG monitoring.

Use substances which do not have the disadvantage of causing torsades de pointes in the presence of hypokalaemia.

N.S.A.I.Ds. (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (> 3 g/day):

Possible reduction in the antihypertensive effect of indapamide.

Risk of acute renal failure in dehydrated patients (decreased glomerular filtration). Hydrate the patient; monitor renal function at the start of treatment.

Angiotensin converting enzyme (A.C.E.) inhibitors:

Risk of sudden hypotension and/or acute renal failure when treatment with an A.C.E. is initiated in the presence of preexisting sodium depletion (particularly in patients with renal artery stenosis).

In hypertension, when prior diuretic treatment may have caused sodium depletion, it is necessary:

— either to stop the diuretic 3 days before starting treatment with the A.C.E. inhibitor, and restart a hypokalaemic diuretic if necessary;

— or give low initial doses of the A.C.E. inhibitor and increase the dose gradually.

In congestive heart failure, start with a very low dose of A.C.E. inhibitor, possibly after a reduction in the dose of the concomitant hypokalaemic diuretic.

In all cases, monitor renal function (plasma creatinine) during the first weeks of treatment with an A.C.E. inhibitor.

Other compounds causing hypokalaemia: amphotericin B (IV), gluco- and mineralo-corticoids (systemic route), tetracosactide, stimulant laxatives:

Increased risk of hypokalaemia (additive effect).

Monitoring of plasma potassium and correction if required. Must be particularly borne in mind in case of concomitant digitalis treatment. Use non-stimulant laxatives.

Baclofen:

Increased antihypertensive effect.

Hydrate the patient; monitor renal function at the start of treatment.

Digitalis preparations:

Hypokalaemia predisposing to the toxic effects of digitalis.

Monitoring of plasma potassium and ECG and, if necessary, adjust the treatment.

Combinations to be taken into consideration:

Potassium-sparing diuretics (amiloride, spironolactone, triamterene):

Whilst rational combinations are useful in some patients, hypokalaemia or hyperkalaemia (particularly in patients with renal failure or diabetes) may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.

Metformin:

Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics. Do not use metformin when plasma creatinine exceeds 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.

Iodinated contrast media:

In the presence of dehydration caused by diuretics, increased risk of acute renal failure, in particular when large doses of iodinated contrast media are used.

Rehydration before administration of the iodinated compound.

Imipramine-like antidepressants, neuroleptics:

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

Calcium (salts):

Risk of hypercalcaemia resulting from decreased urinary elimination of calcium.

Ciclosporin, tacrolimus:

Risk of increased plasma creatinine without any change in circulating ciclosporin levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (systemic route):

Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Pregnancy:

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.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

As a precautionary measure, it is preferable to avoid the use of Indapamide during pregnancy.

Breast-feeding:

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 decrease or even suppression of milk lactation.

Indapamide should not be used during breast-feeding.

Fertility

Reproductive toxicity studies showed no effect on fertility in female and male rats. No effects on human fertility are anticipated.

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.

Summary of safety profile

The most commonly reported adverse reactions are hypersensitivity reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions and maculopapular rashes.

During clinical trials, hypokalaemia (plasma potassium <3.4 mmol/l) was seen in 10 % of patients and < 3.2 mmol/l in 4 % of patients after 4 to 6 weeks treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.23 mmol/l.

The majority of adverse reactions concerning clinical or laboratory parameters are dose-dependent.

Tabulated summary of adverse reactions

The following undesirable effects have been observed with indapamide during treatment ranked under the following frequency:

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 (>1/100,000 to <1/10,000), not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

Symptoms

Indapamide has been found free of toxicity at up to 40 mg, i.e. 27 times the therapeutic dose.

Signs of acute poisoning take the form above all of water/electrolyte disturbances (hyponatraemia, hypokalaemia). Clinically, possibility of nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusion, polyuria or oliguria possibly to the point of anuria (by hypovolaemia).

Management

Initial measures involve the rapid elimination of the ingested substance(s) by gastric wash-out and/or administration of activated charcoal, followed by restoration of water/electrolyte balance to normal in a specialised centre.

Pharmacotherapeutic group: Sulfonamides, plain

ATC code: C 03 BA 11

Mechanism of action

Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to thiazide diuretics, which acts by inhibiting the reabsorption of sodium in the cortical dilution segment. It increases the urinary excretion of sodium and chlorides and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing urine output and having an antihypertensive action.

Pharmacodynamic effects

Phase II and III studies using monotherapy have demonstrated an antihypertensive effect lasting 24 hours. This was present at doses where the diuretic effect was of mild intensity.

The antihypertensive activity of indapamide is related to an improvement in arterial compliance and a reduction in arteriolar and total peripheral resistance.

Indapamide reduces left ventricular hypertrophy.

Thiazide and related diuretics have a plateau therapeutic effect beyond a certain dose, while adverse effects continue to increase. The dose should not be increased if treatment is ineffective.

It has also been shown, in the short-, mid- and long-term in hypertensive patients, that indapamide:

— does not interfere with lipid metabolism: triglycerides, LDL-cholesterol and HDL-cholesterol;

— does not interfere with carbohydrate metabolism, even in diabetic hypertensive patients.

Indapamide 1.5 mg is supplied in a prolonged release dosage based on a matrix system in which the drug substance is dispersed within a support which allows sustained release of indapamide.

Absorption:

The fraction of indapamide released is rapidly and totally absorbed via the gastrointestinal digestive tract.

Eating slightly increases the rapidity of absorption but has no influence on the amount of the drug absorbed.

Peak serum level following a single dose occurs about 12 hours after ingestion, repeated administration reduces the variation in serum levels between 2 doses. Intra-individual variability exists.

Distribution:

Binding of indapamide to plasma proteins is 79%.

The plasma elimination half-life is 14 to 24 hours (mean 18 hours).

Steady state is achieved after 7 days.

Repeated administration does not lead to accumulation.

Metabolism:

Elimination is essentially urinary (70% of the dose) and faecal (22%) in the form of inactive metabolites.

High risk individuals:

Pharmacokinetic parameters are unchanged in renal failure patients.

Indapamide has been tested negative concerning mutagenic and carcinogenic properties.

The highest doses administered orally to different animal species (40 to 8000 times the therapeutic dose) have shown an exacerbation of the diuretic properties of indapamide. The major symptoms of poisoning during acute toxicity studies with indapamide administered intravenously or intraperitoneally were related to the pharmacological action of indapamide, i.e. bradypnoea and peripheral vasodilation.

Reproductive toxicity studies have not shown embryotoxicity and teratogenicity.

Fertility was not impaired either in male or in female rats.

Tablet:

Silica, colloidal anhydrous

Hypromellose

Lactose monohydrate

Magnesium stearate

Povidone

Film-coating:

Glycerol

Hypromellose

Macrogol 6000

Magnesium stearate

Titanium dioxide

10, 14, 15, 20, 30, 50, 60, 90, 100 tablets in blisters (PVC/aluminium).

Not all pack sizes may be marketed.

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex

France

9th January 1996/25th February 2007 (MRP)

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Natrilix SR is and what it is used for
2. What you need to know before you take Natrilix SR
3. How to take Natrilix SR
4. Possible side effects
5. How to store Natrilix SR
6. Contents of the pack and other information

• if you are allergic to indapamide or any other sulfonamide or to any of the other ingredients of this medicine (listed in section 6),
• if you have severe kidney disease,
• if you have severe liver disease or suffer from a condition called hepatic encephalopathy (degenerative disease of the brain),
• if you have low potassium levels in your blood.

Talk to your doctor or pharmacist before taking Natrilix SR:

• if you have liver problems,
• if you have diabetes,
• if you suffer from gout,
• if you have any heart rhythm problems or problems with your kidneys,
• if you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase of pressure in your eye and can happen within hours to weeks of taking Natrilix SR. This can lead to permanent vision loss, if not treated. If you earlier have had a penicillin or sulfonamide allergy, you can be at higher risk of developing this,
• if you have muscle disorders including muscle pain, tenderness, weakness or cramps,
• if you need to have a test to check how well your parathyroid gland is working.

You should tell your doctor if you had photosensitivity reactions. Your doctor may give you blood tests to check for low sodium or potassium levels or high calcium levels.

If you think any of these situations may apply to you or you have any questions or doubts about taking your medicine, you should consult your doctor or pharmacist. Athletes should be aware that this medicine contains an active ingredient, which may give a positive reaction in doping tests.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. You should not take Natrilix SR with lithium (used to treat depression) due to the risk of increased levels of lithium in the blood.

Make sure to tell your doctor if you are taking any of the following medicines, as special care may be required:

• medicines used for heart rhythm problems (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium),
• medicines used to treat mental disorders such as depression, anxiety, schizophrenia… (e.g. tricyclic antidepressants, antipsychotic drugs, neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol)),
• bepridil (used to treat angina pectoris, a condition causing chest pain),
• cisapride (used to treat reduced movement of the gullet and stomach),
• diphemanil (used to treat gastro-intestinal problems
• antibiotics used to treat bacterial infections (e.g. sparfloxacin, moxifloxacin, erythromycin by injection),
• vincamine by injection (used to treat symptomatic cognitive disorders in elderly including memory loss),
• halofantrine (antiparasitic drug used to treat certain types of malaria),
• pentamidine (used to treat certain types of pneumonia),
• antihistamines used to treat allergic reactions, such as hay fever (e.g. mizolastine, astemizole, terfenadine),
• non-steroidal anti-inflammatory drugs for pain relief (e.g. ibuprofen) or high doses of acetylsalicylic acid,
• angiotensin converting enzyme (ACE) inhibitors (used to treat high blood pressure and heart failure),
• amphotericin B by injection (anti-fungal medicines),
• oral corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis,
• stimulant laxatives,
• baclofen (to treat muscle stiffness occurring in diseases such as multiple sclerosis),
• allopurinol (for the treatment of gout),
• potassium-sparing diuretics (e.g. amiloride, spironolactone, triamterene),
• metformin (to treat diabetes),
• iodinated contrast media (used for tests involving X-rays),
• calcium tablets or other calcium supplements,
• ciclosporin, tacrolimus or other medicines to depress the immune system after organ transplantation, to treat autoimmune diseases, or severe rheumatic or dermatological diseases,
• tetracosactide (to treat Crohn’s disease),
• methadone (used to treat addiction).

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

This medicine is not recommended during pregnancy. When a pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible. Please tell your doctor if you are pregnant or wish to become pregnant. The active ingredient is excreted in milk. Breast-feeding is not recommended if you are taking this medicine.

This medicine can cause side effects due to lowering of the blood pressure such as dizziness or tiredness (see section 4). These side effects are more likely to occur after initiation of the treatment and after dose increases. If this occurs, you should refrain from driving and other activities requiring alertness. However, under good control, these side effects are unlikely to occur.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

If you have taken too many tablets, contact your doctor or pharmacist immediately.

A very large dose of Natrilix SR could cause nausea (feeling sick), vomiting, low blood pressure, cramps, dizziness, drowsiness, confusion and changes in the amount of urine produced by the kidneys.

If you forget to take a dose of your medicine, take the next dose at the usual time.

Do not take a double dose to make up for a forgotten dose.

As the treatment for high blood pressure is usually life-long, you should discuss with your doctor before stopping this medicinal product.

• Angioedema and/or urticaria. Angioedema is characterised by swelling of the skin of extremities or face, swelling of the lips or tongue, swelling of the mucous membranes of the throat or airways resulting in shortness of breath or difficulty of swallowing. If this occurs, contact your doctor immediately. (Very rare) (may affect up to 1 in 10,000 people)
• Severe skin reactions including intense skin rash, reddening of the skin over your whole body, severe itching, blistering, peeling and swelling of the skin, inflammation of mucous membranes (Stevens Johnson Syndrome) or other allergic reactions, (Very rare) (may affect up to 1 in 10,000 people)
• Life-threatening irregular beat. (Not known)
• Inflamed pancreas which may cause severe abdominal and back pain accompanied with feeling very unwell (Very rare) (may affect up to 1 in 10,000 people)
• Disease of the brain caused by liver illness (Hepatic encephalopathy) (Not known)
• Inflammation of the liver (Hepatitis) (Not known)
• Muscle weakness, cramps, tenderness or pain and particularly, if at the same time, you feel unwell or have a high temperature it may be caused by an abnormal muscle breakdown (Not known)

In decreasing order of frequency, other side effects can include:

Common (may affect up to 1 in 10 people):

• Red raised skin rash;
• Allergic reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions;
• Low potassium in the blood.

Uncommon (may affect up to 1 in 100 people):

• Vomiting;
• Red pinpoints on skin (Purpura);
• Low sodium in the blood that may lead to dehydration and low blood pressure;
• Impotence (inability to obtain or maintain an erection).

Rare (may affect up to 1 in 1000 people):

• Feeling of tiredness, headache, pins and needles (paraesthesia), vertigo;
• Gastro-intestinal disorders (such as nausea, constipation), dry mouth;
• Low chloride in the blood;
• Low magnesium in the blood.

Very rare (may affect up to 1 in 10,000 people):

• Changes in blood cells, such as thrombocytopenia (decrease in the number of platelets which causes easy bruising and nasal bleeding), leucopenia (decrease of white blood cells which may cause unexplained fever, soreness of the throat or other flu-like symptoms — if this occurs, contact your doctor) and anaemia (decrease in red blood cells);
• High level of calcium in blood;
• Heart rhythm irregularities (causing palpitations, feeling of the heart pounding), low blood pressure;
• Kidney disease (causing symptoms of tiredness, increased need to urinate, itchy skin, feeling sick, swollen extremities);
• Abnormal hepatic function.

Not known (frequency cannot be estimated from the available data):

• Fainting.
• If you suffer from systemic lupus erythematosus (a disorder of the immune system leading to inflammation and damage to the joints, tendons and organs with symptoms including skin rashes, tiredness, loss of appetite, weight gain and joint pain), this might get worse.
• Cases of photosensitivity reactions (change in skin appearance) after exposure to the sun or artificial UVA have also been reported.
• Short sightedness (myopia).
• Blurred vision.
• Visual impairment.
• Decrease in vision or pain in your eyes due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).
• Changes may occur in your blood and your doctor may need to give you blood tests to check your condition.
  The following changes in laboratory parameters may occur:
  • increase in uric acid, a substance which may cause or worsen gout (painful joint(s) especially in the feet),
  • increase in blood glucose levels in diabetic patients,
  • increased levels of liver enzymes.
• Abnormal ECG heart tracing.

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

The active substance is indapamide. Each tablet contains 1.5mg of indapamide.

The other ingredients are:

• tablet core: anhydrous colloidal silica (E551), hypromellose (E464), lactose monohydrate, magnesium stearate (E470B), povidone
• film-coating: glycerol (E422), hypromellose (E464), macrogol 6000, magnesium stearate (E470B), titanium dioxide (E171).

This medicine is a white, round prolonged-release film-coated tablet.

The tablets are available in blisters of 10, 14, 15, 20, 30, 50, 60, 90 or 100 tablets packed in a cardboard box.

Not all pack sizes may be marketed.

Les Laboratoires Servier
50, rue Carnot
92284 Suresnes cedex
France

Servier (Ireland) Industries Ltd
Gorey Road
Co. Wicklow
Arklow
IRELAND

Address

Sefton House, Sefton Park, Bells Hill, Stoke Poges, Slough, SL2 4JS, UK

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+44 (0)1753 663456

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Telephone

+44 (0)1753 662744

Medical Information Direct Line

+44 (0)1753 666409