Ramimed Kombi of the tab. 5mg/25mg No. 30

Pharmacological properties

action Mechanism. ramiprit. ramiprilat, an active metabolite of pro-medicine — the ramiprila, is i dipeptidilkarboksipeptidaza enzyme inhibitor (synonyms: apf, ii kinase). in blood plasma and fabrics this enzyme catalyzes transformation of angiotensin i into ii angiotensin (active vasoconstrictive agent) and splitting of an active vazodilatator of bradykinin. reduction of formation of ii angiotensin and oppression lead splitting of bradykinin to vasodilatation. as ii angiotensin also stimulates release of Aldosteronum, ramiprilat leads to reduction of secretion of Aldosteronum. reaction to monotherapy by inhibitors apf on average less expressed at patients of negroid race (Afro-Caribbean origin) with ag (population of which the low level of renin is characteristic at ag), than at patients who are representatives of other races.

Hydrochlorothiazide. The hydrochlorothiazide is a thiazide diuretic. As for thiazide diuretics, the mechanism of their antihypertensive action is still finally not found out. They suppress a reabsorption of ions of sodium and chlorine in distal tubules. The strengthened renal excretion of these ions is followed by increase in an uropoiesis (owing to osmotic binding of water). Removal of potassium and magnesium also increases whereas removal of uric acid decreases. Possible mechanisms of hypotensive action of a hydrochlorothiazide consist in change of sodium balance, reduction of volume of extracellular liquid and blood plasma, change of resistance of renal vessels or decrease in reaction to noradrenaline and angiotensin II.

Pharmacodynamics

Ramipril. Antihypertensive properties. Reception of a ramipril leads to considerable decrease in OPSS. As a rule, significant changes in a renal plazmotok or glomerular filtration rate do not occur. Use of a ramipril for patients with AG leads to decrease in the ABP both in horizontal, and in vertical position of the patient, and is not followed by compensatory increase in ChSS.

At most of patients the antihypertensive effect occurs in 1–2 h after oral administration of medicament in a single dose. The maximum effect after oral administration of a single dose usually occurs in 3–6 h. The antihypertensive effect after reception of a single dose usually remains during 24 h

At long-term treatment using a ramipril the maximum antihypertensive effect develops in 3–4 weeks. It is proved that at long therapy the antihypertensive effect remains within 2 years.

Sudden termination of reception of a ramipril does not cause fast and excessive increase in the ABP (ricochet phenomenon).

Heart failure. It is proved that applied as addition to traditional therapy with diuretics and, in case of need, cardiac glycosides ramiprit it is effective for patients with heart failure of the II-IV class on classification of NYHA. Drug shows beneficial influence on a warm hemodynamics (pressure decrease of filling of the left and right ventricles, OPSS, increase in warm emission and improvement of cardiac index). It also reduces neuroendocrinal activation.

Hydrochlorothiazide. As for a hydrochlorothiazide, the beginning of diuretic effect comes approximately in 2 h and proceeds during 6–12 h, and the maximum effect is reached in 4 h. The antihypertensive effect is reached in 3–4 days of treatment and can last for 1 week after completion of treatment.

Antihypertensive effect is followed by insignificant increase in glomerular filtration rate, vascular resistance of the renal course and activity of renin in blood plasma.

Simultaneous use of a ramipril and hydrochlorothiazide. Use of this combination leads to more considerable decrease in the ABP, than use of each of active ingredients separately. The combined use of a ramipril and hydrochlorothiazide reduces potassium loss which accompanies diuretic effect probably owing to oppression of activity the system renin-angiotensin-aldosteronovoy (SRAA). Combination of APF inhibitor with thiazide diuretic causes synergy effect and also reduces risk of emergence of the hypopotassemia caused by use of the diuretic.

Pharmacokinetics

Ramipril. Absorption. After oral administration ramiprit quickly it is soaked up in a GIT. The C _max in blood plasma is reached during 1 h. Considering amount of the substance revealed in urine, extent of absorption makes not less than 56% and for it significantly existence of food in a GIT does not influence. The bioavailability of an active metabolite of the ramiprilat after oral administration ramiprit 2.5 and 5 mg in a dose is 45%.

C _max in blood plasma of the ramiprilat, the only active metabolite of a ramipril, it is reached in 2–4 h after reception of a ramipril. After use of a ramipril in usual doses of 1 times a day the equilibrium concentration of the ramiprilat in blood plasma is reached for the 4th day of treatment.

Distribution. Linking of a ramipril with proteins of blood plasma makes about 73%, and the ramiprilat — 56%.

Metabolism. Ramipril is almost completely metabolized to the ramiprilat, diketopiperazine ether, diketopiperazine acid and glucuronides of a ramipril and the ramiprilat.

Removal. Removal of metabolites happens mainly by renal excretion. Decrease in concentration of the ramiprilat in blood plasma is multiphase. Because of the powerful saturating linking with APF and slow dissociation on communication with enzyme ramiprilat possesses the prolonged terminal phase of removal at very low concentration in blood plasma.

After reception of repeated doses of a ramipril of 1 times a day effective T _½ makes 13–17 h at a dose of 5-10 mg and more for low doses (1.25-2.5 mg). The difference is caused by the fact that the ability of enzyme to binding with ramiprilaty is saturable.

At oral administration of a single dose of drug, its metabolite was revealed in breast milk. However it is unknown what effect has reception of repeated doses.

Patients with a renal failure (see USE). At patients with a renal failure the renal excretion of the ramiprilat is reduced, and the renal clearance of the ramiprilat is proportional to clearance of creatinine. It leads to increase in concentration of the ramiprilat in blood plasma which decreases more slowly, than at persons with normal function of kidneys.

Patients with an abnormal liver function (see USE). At persons with an abnormal liver function the metabolism of a ramipril with formation of the ramiprilat is slowed down because of decrease of the activity of hepatic esterases, and the level of a ramipril in blood plasma at these patients is increased. However the C _max ramiprilat at these patients did not differ from those at persons with normal function of a liver.

Hydrochlorothiazide. Absorption. After oral administration in a GIT 70% of a hydrochlorothiazide are soaked up. The C _max a hydrochlorothiazide in blood plasma is reached in 1.5-5 h

Distribution. For a hydrochlorothiazide the linking with proteins of blood plasma makes about 40%.

Metabolism. The hydrochlorothiazide is metabolized in a liver in very insignificant quantities.

Removal. The hydrochlorothiazide is allocated with kidneys almost completely (95%) in not changed look; 50–70% of a single dose are removed during 24 h T _½ make 5–6 h

Patients with a renal failure (see USE). At persons with a renal failure the renal excretion of a hydrochlorothiazide is reduced, and the renal clearance of a hydrochlorothiazide is proportional to clearance of creatinine. It leads to increase in concentration of a hydrochlorothiazide in blood plasma which decreases more slowly, than at persons with healthy kidneys.

Patients with an abnormal liver function (see USE). At patients with cirrhosis the pharmacokinetics of a hydrochlorothiazide does not undergo significant changes.

did not conduct researches on studying pharmacokinetics of a hydrochlorothiazide at patients with heart failure.

Ramipril and hydrochlorothiazide. Simultaneous use of a ramipril and hydrochlorothiazide did not affect their bioavailability. The bioequivalent medicaments containing separate active ingredients can consider the combined drug.

Indication

Ramimed. treatment at ag. prevention of cardiovascular diseases — decrease in cardiovascular incidence and lethality at patients with:

• profound cardiovascular disease of aterotrombotichesky genesis (existence in the anamnesis of an ischemic heart disease or stroke or disease of peripheral vessels);
• diabetes, having at least one factor of cardiovascular risk (see. Pharmacological PROPERTIES).

Treatment in a disease of kidneys:

• an initial glomerular diabetic nephropathy to which presence of a microalbuminuria testifies;
• expressed glomerular diabetic nephropathy to which presence of a macroproteinuria, at the patients having at least one factor of cardiovascular risk (testifies see. Pharmacological PROPERTIES);
• expressed glomerular not diabetic nephropathy to which presence of a macroproteinuria of ≥3 g/days (testifies see. Pharmacological PROPERTIES).

Treatment in the heart failure which is followed by clinical manifestations. Secondary prevention after the postponed acute myocardial infarction: decrease in lethality at the acute stage of a myocardial infarction at patients with clinical signs of heart failure at an initiation of treatment more than in 48 h after developing of an acute myocardial infarction.

Ramimed Kombi. Treatment at AG. Use of this fixed combination is shown to patients at whom the ABP is not controlled properly at monotherapy ramiprily or a hydrochlorothiazide.

Use

Ramimed. medicament for oral administration. ramimed it is recommended to accept daily at the same time. the medicament can be taken to, in time and after a meal as meal does not affect bioavailability of drug. ramimed it is necessary to swallow of tablets entirely, washing down with water. they cannot be chewed or crushed.

Adult. The patients applying diuretics. In an initiation of treatment medicament Ramimed can arise arterial hypotension which development is more probable at the patients who are at the same time receiving diuretics. In similar cases it is recommended to show care as at these patients the reduction of OCK and/or amount of electrolytes is possible.

if it is possible (see. Special INSTRUCTIONS).

At patients with AG which cannot cancel diuretic with a dose 1.25 mg. It is necessary to control carefully function of kidneys and level of potassium in blood. Further medicament dosing Ramimed needs to be korrigirovat depending on the AD target level.

AG. The dose should be selected individually, depending on features of a condition of the patient (see. Special INSTRUCTIONS) and results of control measurements of the ABP. Ramimed it is possible to apply in monotherapy or in a combination with other classes of antihypertensive medicines.

Initial dose. Drug treatment Ramimed should be begun gradually, starting with recommended an initial dose of 2.5 mg/days. Patients with considerable activation of RAAS after reception of an initial dose of medicament can have a considerable decrease in the ABP. For such patients the recommended dose makes 1.25 mg, and their treatment is required to be begun under medical control (see. Special INSTRUCTIONS).

Titration of a dose and maintenance dose. Dose it is possible to double each 2–4 weeks before achievement of the AD target level; the maximum dose of the medicament Ramimed makes 10 mg/days. As a rule, the medicament is taken 1 time a day.

Prevention of cardiovascular diseases. Initial dose. The recommended initial dose of the medicament Ramimed makes 2.5 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament the dose should be raised gradually. It is recommended to double a dose in 1–2 weeks of treatment, and then — through 2–3 weeks — to raise it to a target maintenance dose of 10 mg of 1 times a day.

Also see the above-stated information concerning medicament dosing for the patients receiving diuretics.

Treatment in diseases of kidneys

At patients with diabetes and a microalbuminuria

Initial dose. The recommended initial dose of the medicament Ramimed makes 1.25 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament at further treatment the dose is raised. In 2 weeks of therapy about 2.5 mg are recommended to double a single dose, and then — up to 5 mg in 2 weeks of treatment.

At patients with diabetes and not less than one factor of cardiovascular risk

Initial dose. The recommended initial dose of the medicament Ramimed makes 2.5 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual tolerance of medicament at further treatment the dose is raised. In 1–2 weeks of treatment about 5 mg are recommended to double a dose of the medicament Ramimed, and then — to 10 mg in 2–3 weeks of therapy. The target daily dose makes 10 mg.

At patients with not diabetic nephropathy to which presence of a macroproteinuria of ≥3 g/days

Initial dose testifies. The recommended initial dose of the medicament Ramimed makes 1.25 mg of 1 times a day.

Titration of a dose and maintenance dose. Depending on individual shipping the patient of medicament at further treatment the dose is raised. In 2 weeks of treatment about 2.5 mg are recommended to double a single dose, and then — to 5 mg in 2 weeks of treatment.

Heart failure with clinical manifestations

Initial dose. For patients whose condition was stabilized after treatment by diuretics the recommended initial dose makes 1.25 mg/days

Titration of a dose and a maintenance dose. A dose of the medicament Ramimed each 1–2 weeks before achievement of the maximum daily dose titrate by its doubling 10 mg. It is desirable to distribute a dose on 2 receptions.

Secondary prevention after the postponed acute myocardial infarction in the presence of heart failure

Initial dose. In 48 h after developing of a myocardial infarction to patients whose condition clinically and hemodynamically steadily, 2 times a day within 3 days appoint an initial dose of 2.5 mg. If the initial dose of 2.5 mg is transferred badly, then it is necessary to apply a dose of 1.25 mg 2 times a day within 2 days with the subsequent increase to 2.5 and 5 mg 2 times a day. If it is impossible to raise a dose to 2.5 mg 2 times a day, treatment should be cancelled.

Also see the above-stated information concerning medicament dosing for the patients receiving diuretics.

Titration of a dose and maintenance dose. Further a daily dose 2 times a day increase by its doubling at an interval of 1–3 days to achievement of a target maintenance dose 5 mg.

At an opportunity a maintenance dose is divided into 2 receptions.

If cannot raise a dose to 2.5 mg 2 times a day, treatment should be cancelled. Experience of treatment of patients with heavy (the IV functional class on classification of NYHA) heart failure right after a myocardial infarction is still not enough. If nevertheless the decision on treatment of such patients is made by this drug, it is recommended to begin therapy with a dose of 1.25 mg of 1 times a day and any its increase to carry out with extreme care.

Special categories of patients

Patients with a renal failure. The daily dose for patients with a renal failure depends on an indicator of clearance of creatinine (see. Pharmacological PROPERTIES):

• if the clearance of creatinine is ≥60 ml/min., there is no need for correction of an initial dose (2.5 mg/days), and the maximum daily dose makes 10 mg;
• if the clearance of creatinine is 30–60 ml/min., there is no need for correction of an initial dose (2.5 mg/days), and the maximum daily dose makes 5 mg;
• if the clearance of creatinine is 10–30 ml/min., the initial dose makes 1.25 mg/days, and the maximum daily dose — 5 mg;
• patients about AG which are on a hemodialysis: at a hemodialysis ramiprit it is removed slightly; the initial dose makes 1.25 mg, and the maximum daily dose — 5 mg; the medicament should be taken in several hours after holding a session of a hemodialysis.

Patients with an abnormal liver function (see. Pharmacological PROPERTIES). Drug treatment Ramimed of patients with abnormal liver functions should be begun under careful medical control, and the maximum daily dose in such cases has to make 2.5 mg.

Patients of advanced age. The initial dose has to be lower, and further titration of a dose should be carried out more gradually, considering a high probability of emergence of side effects, especially at very old and weak patients. In such cases appoint the minimum initial dose — 1.25 mg of a ramipril.

Children. Ramimed is not recommended to use medicament at children as data on efficiency and safety of this medicament for such patients are not enough.

Ramimed Kombi. For oral administration. 1 time a day at the same time is recommended to take the drug, it is desirable in the morning.

can take the Drug to, in time and after a meal as meal does not affect its bioavailability (see Pharmacokinetics). It is necessary to swallow of tablets entirely, washing down with water. They cannot be chewed or crushed.

Adult. To korrigirovat a dose individually, depending on features of the patient (see. Special INSTRUCTIONS) and ABP level. Use of the fixed combination of a ramipril and a hydrochlorothiazide, as a rule, is recommended only after titration of doses of each of its separate components.

treatment with the minimum possible dose. In case of need the dose can be raised to achievement of a target indicator of the ABP gradually. The maximum allowed dose makes 10 mg of a ramipril and 25 mg of a hydrochlorothiazide a day (to apply a combination of medicaments in the corresponding dosage).

Special groups of patients

Patients receiving diuretics. It is recommended to show care as the patients receiving diuretics in an initiation of treatment can have an arterial hypotension. Before beginning therapy with drug, it is necessary to lower a dose of diuretic or to stop its use.

Patients with a renal failure. Because of existence of a hydrochlorothiazide component medicament is contraindicated to patients with a heavy renal failure (clearance of creatinine of 30 ml/min.) (see CONTRAINDICATIONS). Lower doses of medicament can be shown to patients with a renal failure. Patients with clearance of creatinine of 30-60 ml/min. should be treated only using a low dose of the fixed combination ramiprila / a hydrochlorothiazide after monotherapy ramiprily. The maximum daily dose makes 5 mg of a ramipril and 25 mg of a hydrochlorothiazide.

Patients with an abnormal liver function. At persons with a slight and moderate abnormal liver function the therapy should be begun only under careful medical control. The maximum daily dose in such cases makes 2.5 mg of a ramipril and 12.5 mg of a hydrochlorothiazide. Drug is contraindicated in cases of a heavy abnormal liver function (see CONTRAINDICATIONS).

Patients of advanced age. The initial dose has to be lower, especially at very old and weak patients, and further titration of a dose should be carried out more gradually, considering a high probability of emergence of side reactions.

Children. Children and teenagers as there are not enough data on its efficiency and safety of use for such patients are not recommended to appoint drug.

Contraindication

Hypersensitivity to active ingredient or any of the excipients which are a part of medicament or to other inhibitors apf. existence in the anamnesis of a Quincke's disease (the hereditary, idiopathic or earlier postponed against the background of use inhibitors apf or antagonists of receptors of ii angiotensin). a considerable bilateral stenosis of renal arteries or a renal artery stenosis in the presence of the only kidney. the pregnancy period (see use during pregnancy and feeding by a breast). ramiprit it is not necessary to apply to patients with arterial hypotension or hemodynamically unstable states. it is not necessary to apply together with the medicaments containing aliskiren, to patients with diabetes or a moderate or heavy renal failure (glomerular filtration rate of 60 ml/min). it is necessary to avoid simultaneous use of inhibitors apf and extracorporal methods of treatment which lead to contact of blood with negatively charged surfaces as such use can lead to anaphylactoid reactions of heavy degree (see interactions). such extracorporal methods of treatment include dialysis or haemo filtration with use of certain membranes with high hydraulic permeability (for example polyacrylonitrile) and aferez LDL using a sulfate dextran.

For Ramimed Kombi also: hypersensitivity to a hydrochlorothiazide, other thiazide diuretics, streptocides. Anury resistant to treatment, hypopotassemia or hypercalcemia, refractory hyponatremia, symptomatic hyperuricemia (gout). Heavy renal failures (clearance of creatinine of 30 ml/min.) at patients to whom the hemodialysis is not carried out. Clinically significant disturbances of electrolytic balance which course can worsen during treatment (see. Special INSTRUCTIONS). Heavy abnormal liver functions, hepatic encephalopathy.

Side effects

Profile of medicament safety of a ramipril contains data on constant cough and the reactions caused by arterial hypotension. treat serious side reactions: a Quincke's disease, a hyperpotassemia, an abnormal liver function or kidneys, pancreatitis, heavy reactions from skin and a neutropenia/agranulocytosis.

+ the hydrochlorothiazide contains data on side effects which arise owing to arterial hypotension and/or reduction of OCK owing to increase in a diuresis. Ramiprit active ingredient can cause constant cough whereas active ingredient a hydrochlorothiazide can break metabolism of glucose, fats and uric acid. Both substances have irreversible effect on potassium level in blood plasma. The Quincke's disease or anaphylactoid reactions, abnormal liver functions or kidneys, pancreatitis, heavy reactions belong to heavy side reactions from skin and a neutropenia/agranulocytosis.

from heart: myocardium ischemia, including stenocardia or a myocardial infarction; tachycardia; arrhythmia; feeling of the strengthened heartbeat; peripheral hypostases.

from the system of blood and lymphatic system: an eosinophilia, reduction of quantity of leukocytes (including a neutropenia or an agranulocytosis), reduction of quantity of erythrocytes, decrease in level of hemoglobin, reduction of quantity of thrombocytes, insufficiency of marrow, a pancytopenia, hemolytic anemia. For medicament ramiprit + a hydrochlorothiazide also: aplastic anemia, haemo concentration in case of a liquid delay.

from nervous system: headache, dizziness, paresthesias, ageusia, dysgeusia, tremor, balance disturbance, cerebral ischemia, including ischemic stroke and tranzitorny ischemic attack; disturbances of psychomotor functions; burning sensation; parosmiya. For medicament ramiprit + a hydrochlorothiazide also: vertigo, spasms, disorientation.

from an organ of sight: a disorder of vision, including illegibility of sight, conjunctivitis. For medicament ramiprit + a hydrochlorothiazide also: a xanthopsia, reduction of lacrimation owing to action of a hydrochlorothiazide.

from an organ of hearing and balance: hearing disorder, sonitus.

Respiratory, thoracic and mediastinal disorders: the unproductive irritating cough, bronchitis, sinusitis, short wind, a bronchospasm, including aggravation OH; congestion of a nose. For medicament ramiprit + a hydrochlorothiazide also: an allergic alveolitis, a neocardial fluid lungs owing to action of a hydrochlorothiazide.

from digestive system: the inflammatory phenomena in a GIT, digestive disturbances, discomfort in a stomach, dyspepsia, diarrhea, nausea, vomiting, pancreatitis (in isolated cases it was reported about lethal consequences at use of APF inhibitors), increase in level of enzymes of a pancreas, a Quincke's disease of a small intestine, pain in an upper part of a stomach, including gastritis, a constipation, dryness in a mouth, a glossitis, stomatitis. For medicament ramiprit + a hydrochlorothiazide also: an ulitis and a sialadenitis owing to action of a hydrochlorothiazide.

from kidneys and urinary tract: a renal failure, including OPN; increase in an uropoiesis, deterioration in a course of a background proteinuria, increase in level of urea in blood; increase in level of creatinine in blood. For medicament ramiprit + a hydrochlorothiazide also: a renal failure, interstitial nephrite owing to action of a hydrochlorothiazide, a hyperuricemia which can provoke gouty attacks at patients with an asimptomny course of the disease.

from skin and hypodermic fabrics: rash, in particular makulopapulezny, Quincke's disease; in very exceptional cases — disturbance of passability of airways owing to a Quincke's disease which can have a lethal outcome; an itching, a hyperhidrosis, exfoliative dermatitis, a small tortoiseshell, an onycholysis, reaction of photosensitivity, a toxic epidermal necrolysis, Stephens's syndrome — Johnson, a multiformny erythema, a pempigus, aggravation of a course of psoriasis, psoriasis dermatitis, a pemfigoidny or lichenoid dieback or an enantema, an alopecia. For medicament ramiprit + a hydrochlorothiazide also: dieback (in particular makulopapulezny), psoriasis dermatitis; a system lupus erythematosus owing to action of a hydrochlorothiazide.

from the musculoskeletal system and connective tissue: muscular spasms, myalgia, arthralgia. For medicament ramiprit + a hydrochlorothiazide also: muscle weakness, musculoskeletal constraint, tetanic spasms owing to action of a hydrochlorothiazide.

from an endocrine system: syndrome of inadequate secretion of antidiuretic hormone (SISAH).

Metabolic and alimentary disturbances: increase in level of potassium in blood, anorexia, a loss of appetite, decrease in level of sodium in blood. For medicament ramiprit + a hydrochlorothiazide also: diabetes decompensation; decrease in a glyukozotolerantnost that can cause a demonstration of latent diabetes, increase in level of glucose in blood; increase in level of uric acid; exacerbation of gout, increase in level XC and/or TG as a result of influence of a hydrochlorothiazide; decrease in level of potassium in blood plasma owing to action of a hydrochlorothiazide; increase in level of potassium in blood; glucosuria; metabolic alkalosis; a gipokhloremichesky alkalosis that can induce hepatic encephalopathy or a hepatic coma; hypochloraemia; hypomagnesiemia; hypercalcemia; dehydration owing to influence of a hydrochlorothiazide; feeling of thirst.

from vessels: arterial hypotension, orthostatic decrease in the ABP, faints, feeling of inflows, stenosis of vessels, hypoperfusion, vasculitis, Reynaud's phenomenon. For medicament ramiprit + a hydrochlorothiazide also: thrombosis owing to considerable reduction of OCK.

Disturbance of the general state: stethalgia, fatigue, pyrexia, asthenia.

from the immune system: anaphylactic and anaphylactoid reactions, increase in level of antinuclear antibodies. For medicament ramiprit + a hydrochlorothiazide also: necrotizing angiitis, respiratory distress, including pneumonitis, acute anaphylaxis, purpura.

from a gepatobiliarny system: increase in level of liver enzymes and/or conjugates of bilirubin, cholestatic jaundice, damages of hepatic cells, OPN, cholestatic or cytolytic hepatitis (in exceptional cases — with a lethal outcome). For medicament ramiprit + a hydrochlorothiazide also: calculous cholecystitis as a result of action of a hydrochlorothiazide.

from a reproductive system and mammary glands: tranzitorny erectile impotence, decrease in a libido, gynecomastia. For medicament ramiprit + a hydrochlorothiazide also: sexual disorders.

from mentality: decrease in mood, uneasiness, nervousness, concern, sleep disorders, including drowsiness, a condition of confusion of consciousness, disturbance of attention. For medicament ramiprit + a hydrochlorothiazide also: apathy, changes of mood.

Special instructions

Needs observation of patients in time to reveal clinical signs of disturbance of water-salt balance (for example a hypovolemia, a hyponatremia, a gipokhloremichesky alkalosis, a hypomagnesiemia or a hypopotassemia) which can develop in case of simultaneous diarrhea or vomiting. at such patients it is necessary to control periodically the level of electrolytes in blood plasma. in warm season the persons with hypostases can have a hyponatremia due to blood fluidifying.

In hepatic disorders and to patients with the progressing diseases of a liver of a tiazida should be applied with care as these medicaments can cause an intra hepatic cholestasia, and even the minimum changes of water-salt balance are capable to provoke development of a hepatic coma. The hydrochlorothiazide is contraindicated to patients with a heavy liver failure.

Special categories of patients

Double blockade of RAAS by means of the medicines containing aliskiren. Double blockade of RAAS by the combined use of medicament and an aliskiren is not recommended as at the same time there is an increased risk of developing arterial hypotension, a hyperpotassemia and emergence of changes in function of kidneys.

to Patients with diabetes or renal failures (glomerular filtration rate of 60 ml/min.) the combined use of medicament and an aliskiren contraindicated (see CONTRAINDICATIONS).

Patients who have an extra risk of developing of arterial hypotension

At patients with substantial increase of activity of RAAS the risk of sudden considerable decrease in the ABP and deterioration in function of kidneys owing to oppression of APF, especially exists if APF inhibitor or the accompanying diuretic are appointed for the first time or for the first time raise a dose. Significant increase in activity of RAAS demanding medical observation, including constant control of the ABP can be expected, for example, at patients:

• from heavy AG;
• with dekompensirovanny stagnant heart failure;
• with hemodynamically significant obstacle for inflow or outflow of blood from a left ventricle (for example with a stenosis of the aortal or mitral valve);
• with a unilateral renal artery stenosis in the presence of the second functioning kidney;
• at which the lack of liquid or electrolytes exists or can develop (including those who apply diuretics);
• with cirrhosis and/or ascites;
• which are carried out by extensive surgical interventions or during anesthesia using the medicaments causing arterial hypotension.

As a rule, it is recommended to carry out correction of dehydration, a hypovolemia or lack of electrolytes prior to treatment (however for patients with heart failure such corrective measures should be weighed carefully concerning risk of emergence of an overload volume).

Patients with liver diseases. Persons with diseases of a liver have disturbances of electrolytic balance arising in the result of treatment with diuretics, such as hydrochlorothiazide, can lead to development of hepatic encephalopathy.

At patients with abnormal liver functions the response to medicament treatment can be or strengthened or reduced. Besides, at persons with heavy cirrhosis which is followed by hypostases and/or ascites the activity of RAAS can be essential povysh