Pharmacological properties

Pharmacodynamics. lozartan-hydrochlorothiazide. it is proved that the lowering impact on hell of components of medicament additive, thus, medicament more lowers arterial blood pressure, than its components separately. assume that this action is connected with summation of effects of components. besides, because of diuretic effect the hydrochlorothiazide increases activity of renin in blood plasma and Aldosteronum discharge, reduces potassium concentration and increases ii angiotensin level in blood plasma. reception of a lozartan blocks all physiological effects of ii angiotensin and owing to oppression of effects of Aldosteronum promotes reduction of the loss of potassium connected with use of diuretics. lozartan possesses moderate and passing uricosuric action. the hydrochlorothiazide slightly increases the level of uric acid in blood; the combination of a lozartan and a hydrochlorothiazide reduces the hyperuricemia caused by diuretics.

Antihypertensive effect of the medicament Lorista remains during 24 h. The antihypertensive effect remains at continuous use of drug. Except significant decrease in the ABP, therapy by medicament had no clinically significant impact on ChSS. The combination of a lozartan and a hydrochlorothiazide is effective in decrease in the ABP at men and at women, patients of negroid and Caucasian races, patients of an average (65 years) and elderly (65 years) age and also is effective at all stages of AG.

Lozartan. Lozartan — the synthetic antagonist of a receptor of angiotensin II (the AT _{1 type} ) which is applied orally. Angiotensin II, powerful vasoconstrictor, is primary active hormone renin-angiotenzinovoy of a system and an important determinal factor of a pathophysiology of AG. Angiotensin II contacts receptors of AT ₁ which contain in many fabrics (for example unstriated muscles of vessels, adrenal glands, kidneys and heart), and renders several important biological effects, including vasoconstriction and release of Aldosteronum. Lozartan selectively blocks a receptor of AT ₁ . In the conditions of in vitro and in vivo lozartan and it pharmacological an active metabolite — carboxyl acid (E3174) — all physiologically significant effects of angiotensin II irrespective of a source or a way of synthesis block.

Lozartan does not connect

and does not block the receptors of other hormones and ion channels important for regulation of activity of a cardiovascular system. Besides, lozartan does not influence action of APF (kinase of II) which is responsible for bradykinin splitting. Therefore the side effects connected with the increased concentration of bradykinin are not noted. At introduction of a lozartan the negative impact of angiotensin II on formation of renin is braked that leads to increase in activity of renin in blood plasma. Increase in activity of renin leads to increase in level of angiotensin II in blood plasma. Despite these increases, antihypertensive activity and decrease in level of Aldosteronum in blood plasma remain that indicates effective blocking of a receptor of angiotensin II. After the therapy termination lozartany activity of renin in blood plasma and concentration of angiotensin II within 3 days return to norm. Lozartan and his main active metabolite have more significant affinity to a receptor of AT ₁ , than to a receptor of AT ₂ . The active metabolite, by calculations of percent by volume, is 10-40 times more effective, than lozartan.

Lozartan does not influence autonomous reflexes and has no long influence on Norepinephrinum level in blood plasma.

Hydrochlorothiazide. The hydrochlorothiazide is diuretic of a thiazide row. The mechanism of antihypertensive effect of diuretic of a thiazide row is completely unknown. Tiazida influence the renal tubular mechanism of an electrolytic reabsorption, thereby directly increasing excretion of sodium and chlorine approximately in identical quantities. Diuretic influence of a hydrochlorothiazide reduces plasma volume, increases activity of renin in plasma, increases secretion of Aldosteronum with the consecutive growth of indicators of potassium in urine, loss of bicarbonate and decrease in level of potassium in serum. Perhaps, because of blockade system renin-aldosteronovoy co-administration of antagonists of receptors of angiotensin II promotes the reverse loss of potassium connected with diuretic of a thiazide row. After reception strengthening of a diuresis begins during 2 h, reaches peak during 4 h and lasts 6–12 h. The antihypertensive effect lasts no more than 24 h

Pharmacokinetics. Absorption. Lozartan. After oral administration lozartan well is soaked up and exposed to primary metabolism with formation of 1 active carboxyl metabolite and others pharmacological inactive metabolites. The system bioavailability of a lozartan is about 33%. The C _max a lozartan and its active metabolite is reached in 1 and 3–4 h after reception respectively. Meal does not render clinically significant deviations of a pharmacokinetic profile.

Distribution. Lozartan. More than 99% of a lozartan and its active metabolite contact proteins of blood plasma, mainly albumine. The volume of distribution of a lozartan is 34 l. In a research on rats lozartan in small degree or did not get through GEB at all.

Hydrochlorothiazide. The hydrochlorothiazide gets through a placental barrier, does not get through GEB, gets into breast milk.

Biotransformation. Lozartan. About 14% orally or in/in entered doses of a lozartan are metabolized in its active metabolite. After peroral or in/in introductions marked From a lozartan of potassium the radioactivity of plasma is caused by radioactive ¹⁴ generally lozartany and its active metabolite. At 1% of the studied persons lozartan only in insignificant degree turns into an active metabolite.

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Krom of an active metabolite, form inactive metabolites, including 2 major metabolites created by hydroxylation of a butyl chain and a small metabolite of N-2 tetrazole a glucuronide.

Removal. Lozartan. The clearance of a lozartan and its active metabolite respectively is 600 and 50 ml/min. of blood plasma. The clearance of a lozartan and its active metabolite is of kidneys respectively 74 and 26 ml/min. At oral administration with urine 4% of a dose of a lozartan in not changed look and 6% are removed — in the form of an active metabolite. Pharmacokinetic properties of a lozartan and its active metabolite linearly change at use of oral doses of a lozartan of potassium up to 200 mg.

After oral administration of concentration of a lozartan and its active metabolite in blood plasma decrease poliexponentsialno; The T _½ makes about 2 and 6–9 h respectively. At a single dosage of 100 mg/days lozartan, its active metabolite significantly do not collect in blood plasma.

I biliary, and renal excretion play a role in elimination of a lozartan and its active metabolites. After reception of an oral dose marked radioactive ¹⁴ From a lozartan about 35% of radioactivity reveal in urine, and 58% — in Calais.

Hydrochlorothiazide. The hydrochlorothiazide is not metabolized, but quickly allocated with kidneys. When concentration of medicament in blood plasma was controlled during at least 24 h, T _½ made 5.6-14.8 h of blood plasma of a hydrochlorothiazide. At least 61% of an oral dose are removed in not changed look during 24 h

Characteristic at patients

Lozartan-hydrokhlorotiazid. Concentration of a lozartan and its active metabolite in blood plasma and absorption of a hydrochlorothiazide at patients of advanced age with AG considerably do not differ from those which are observed at young patients with AG.

Lozartan. After oral administration at patients with alcoholic cirrhosis and moderate severity of concentration of a lozartan and its active metabolites in blood plasma were easy respectively in 5 and 1.7 times is higher, than at young volunteers.

Indication

Lecheniye ag when monotherapy lozartany or monotherapies by a hydrochlorothiazide is not enough.

Lorista of N 100. Reduction of risk of cardiovascular diseases and lethal outcomes at patients with AG, a hypertrophy of a left ventricle.

Use

can use Drug of the lorist with other antihypertensive drugs. it is necessary to swallow of tablets, washing down with a glass of water. use of medicament does not depend on meal.

AG

At insufficient efficiency of monotherapy by components of medicament can use directly combined drug. A usual initial and maintenance dose for most of patients is 1 tablet of Lorista of N (50/12.5 mg) of 1 times a day. Patients at whom use of 1 tablet of Lorista of N does not give sufficient effect can raise a dose to 2 tablets of Lorista of N of 1 times a day (morning), 1 tablets of Lorista of N 100 or to 1 tablet of Lorista HD (100/25 mg) of 1 times a day (morning).

Maximum hypotensive effect is reached by

within 3–4 weeks of treatment. The maximum recommended dose makes 2 tablets of Lorista of N or 1 tablet of Lorista HD of 1 times a day.

Drug Lorista the N 100 is intended to

for those patients who receive the dose of a lozartan of 100 mg established by titration and who demand additional control of the ABP.

Reduction of risk of cardiovascular diseases and lethal outcomes at patients with AG with a hypertrophy of a left ventricle. The usual initial dose makes 50 mg of a lozartan of 1 times a day. Patients at whom it is not possible to reach target values of the ABP level at reception of a lozartan of 50 mg/days should select therapy using a combination of a lozartan with low doses of a hydrochlorothiazide (12.5 mg) and, if necessary, then to increase a dose to 100 mg lozartana/12.5 mg of a hydrochlorothiazide of 1 times a day. If necessary it is necessary to increase a dose to 100 mg of a lozartan and 25 mg of a hydrochlorothiazide of 1 times a day.

Lorista of N, Lorista N 100 and Lorista HD are the appropriate alternative medicines for patients who otherwise have to accept combined lozartan and a hydrochlorothiazide.

Use for patients with a renal failure and at patients who are on a hemodialysis. With a moderate renal failure (clearance of creatinine of 30-50 ml/min.) of correction of an initial dose it is not required to patients.

Lozartan and a hydrochlorothiazide in tablets is not recommended to be applied at patients who are on a hemodialysis. Lozartan / the hydrochlorothiazide in tablets is contraindicated to patients with a heavy renal failure (clearance of creatinine of 30 ml/min.).

Use for patients with reduction of intravascular volume of the circulating liquid. Correction of deficit of volume of liquid and/or sodium should be carried out before use lozartana / a hydrochlorothiazide in tablets.

Use for patients with a liver failure. Lozartan / the hydrochlorothiazide is contraindicated to patients with a heavy liver failure.

Use for patients of advanced age. As a rule, it is not required to patients of advanced age of dose adjustment.

Contraindication

Hypersensitivity to the lozartan, substances which are sulfonamide derivatives (such as hydrochlorothiazide) or any excipients;

• pregnant women or women who are going to become pregnant (see. Use during pregnancy and feeding by a breast);
• a heavy renal failure (namely — clearance of creatinine of 30 ml/min.);
• anury;
• profound liver failure, cholestasia, obstructive diseases of biliary tract;
• therapeutic resistant hypopotassemia or hypercalcemia;
• steady hyponatremia;
• symptomatic hyperuricemia / gout;
• simultaneous use of an aliskiren for patients with diabetes or a renal failure (SKF of 60 ml/min. / 1.73 m ² ) (see. Special INSTRUCTIONS and INTERACTIONS).

Side effects

Side reactions which can arise during treatment lozartany are classified by

in groups on emergence frequency: very often (1/10); often (1/100, 1/10); infrequently (1/1000, 1/100); seldom (1/10,000, 1/1000); very seldom (1/10,000); it is unknown (it is impossible to count on the available data).

In researches at AG the dizziness was the only side effect connected with active ingredient and was noted at more than 1% of patients (reliable more, than in group of placebo).

from a gepatobiliarny system: seldom — hepatitis.

Change of laboratory indicators: seldom — a hyperpotassemia, increase in the AlAT level.

Additional side effects which were observed at use of one of separate components of medicament and which can be potential side effects of medicament at use of a lozartan of a potassium/hydrochlorothiazide, the following:

Lozartan

from blood and lymphatic system: infrequently — anemia, Shenlyayn's purpura — Genokh, ecchymomas, hemolysis.

from the immune system: seldom — anaphylactic reactions, a Quincke's disease, a small tortoiseshell.

from metabolism and food: infrequently — anorexia, gout.

Mental disturbances: often — insomnia; infrequently — alarm, a disturbing condition, confusion of consciousness, a depression, nightmares, sleep disorders, drowsiness, memory disturbance.

from nervous system: often — a headache, dizziness; infrequently — nervousness, paresthesias, peripheral neuropathy, a tremor, migraine, a syncope.

from an organ of sight: infrequently — turbidity of sight, feeling of burnings/naggers in an eye, conjunctivitis, a disorder of vision.

from an organ of hearing and a vestibular mechanism: infrequently — dizziness and sonitus.

from a cardiovascular system: infrequently — arterial hypotension, orthostatic hypotension, thorax pain, stenocardia, blockade of the II degree, cerebrovascular disturbances, a myocardial infarction, heartbeat, arrhythmias (fibrillation of auricles, sinus bradycardia, tachycardia, ventricular tachycardia, fibrillation of ventricles of heart).

from the vascular system: infrequently — a vasculitis.

from the respiratory system and bodies of mediastinum: often — cough, inflammation of upper airways, congestion of a nose, antritis, changes in nasal bosoms; infrequently — feeling of pharyngeal discomfort, pharyngitis, laryngitis, an asthma, bronchitis, nasal bleeding, rhinitis, disturbance of passability of airways.

from a digestive tract: often — an abdominal pain, nausea, diarrhea, dyspepsia; infrequently — a constipation, a toothache, dryness in a mouth, a meteorism, gastritis, vomiting.

from a gepatobiliarny system: it is unknown — functional disturbances of a liver.

from skin and hypodermic fabrics: sometimes — an alopecia, dermatitis, xeroderma, an erythema, reddening, photosensitivity, an itching, rash, urticaria, the increased sweating.

from a skeletal and muscular system and connective tissues: often — muscular spasms, a dorsodynia, an onychalgia, myalgia; infrequently — hand pain, hypostases of joints, knee pain, bone and muscular pain, shoulder pain, feeling of constraint in joints, an arthralgia, arthritis, a coxalgia, fibromyalgia, muscle weakness, a hip joint pain; very seldom — a rhabdomyolysis.

from kidneys and urinary tract: infrequently — a nocturia, intensive discharge of urine, an infection of urinary tract.

Disturbance from a reproductive system and mammary glands: infrequently — decrease in a libido, impotence.

System disturbances and complications in the injection site: often — increased fatigue, thorax pain; infrequently — a face edema, fervescence.

Change of laboratory indicators: often — a hyperpotassemia, insignificant decrease in level of a hematocrit and hemoglobin; infrequently — insignificant decrease in concentration of residual nitrogen and creatinine; very seldom — increase in activity of liver enzymes and level of bilirubin.

Hydrochlorothiazide

from blood and lymphatic system: infrequently — an agranulocytosis, aplastic anemia, hemolytic anemia, a leukopenia, a purpura, thrombocytopenia.

from the immune system: seldom — anaphylactic reactions.

from metabolism and food: infrequently — anorexia, a hyperglycemia, a hyperuricemia, a hypopotassemia, a hyponatremia.

Mental disorders: infrequently — insomnia, change of mood.

from nervous system: often — a headache.

from an organ of sight: infrequently — temporary turbidity of sight, a xanthopsia.

from the vascular system: infrequently — a necrotizing angiitis (a vasculitis and a skin vasculitis).

from the respiratory system and bodies of mediastinum: infrequently — a respiratory distress, including a pneumonitis and a fluid lungs.

from a digestive tract: infrequently — inflammation of sialadens, intestinal spasms, irritation of a stomach, nausea, vomiting, diarrhea, a constipation.

from a gepatobiliarny system: infrequently — jaundice (intra hepatic cholestatic), pancreatitis.

from skin and hypodermic fabrics: often — photosensitivity, a small tortoiseshell, a toxic epidermal necrolysis; infrequently — Stephens's syndrome — Johnson, the skin reactions reminding a skin form of a system lupus erythematosus, reactivation of a skin form of a lupus erythematosus.

from a skeletal and muscular system and connective tissues: infrequently — muscular spasms.

from kidneys and urinary tract: infrequently — a glucosuria, interstitial nephrite, dysfunction of kidneys, a renal failure.

System disturbances and complications in the injection site: seldom — fervescence, dizziness.

Special instructions

Lozartan. hypersensitivity. developing of a Quincke's disease is possible. it is necessary to establish careful control of patients who in the anamnesis had a Quincke's disease (faces, lips, a throat and/or language).

Arterial hypotension and disturbances of water and electrolytic balance. Patients with deficit of volume of the circulating liquid and/or sodium in an organism owing to intensive use of diuretics, restriction of the use of salt, diarrhea or vomiting can have a symptomatic arterial hypotension, especially after reception of the 1st dose and after increase in a dose. Similar states demand carrying out their correction before use of medicament or decrease in an initial dose.

Disturbance of water and electrolytic balance. At patients with a renal failure as patients with diabetes, and without it, often there are disturbances of electrolytic balance which demand correction. During the clinical trials conducted among patients with diabetes of the II type and a nephropathy, the frequency of emergence of a hyperpotassemia was higher in the group receiving lozartan in comparison with group of placebo. Therefore it is regularly necessary to control potassium concentration in blood plasma and indicators of clearance of creatinine. Especially careful observation is demanded by patients with heart failure and clearance of creatinine from 30 to 50 ml/min. Along with lozartany it is not recommended to apply the kaliysberegayushchy diuretics, additives containing potassium, and salt substitutes with potassium.

Abnormal liver function. Based on pharmacokinetic data which confirm significant increase in concentration of a lozartan in blood plasma at patients with cirrhosis the patients in who anamnesis have abnormal liver functions need to lower a medicament dose. There is no experience of therapeutic use of a lozartan for patients with a heavy liver failure. Therefore lozartan patients cannot accept with a heavy liver failure.

Renal failure. As a result of inhibition system renin-angiotenzinovoy, changes in functioning of kidneys, including a renal failure were observed (in particular at patients at whom work of kidneys depends on functioning system renin-angiotensin-aldosteronovoy, for example in heavy heart failure or presence of background dysfunction of kidneys). As well as at use of other medicaments influencing renin-anitotenzin-aldosteronovuyu a system for patients with a bilateral renal artery stenosis or a renal artery stenosis of the only kidney the increase in level of urea and creatinine in blood serum is observed. Lozartan it is necessary to apply with care at patients with a bilateral stenosis of renal arteries or a renal artery stenosis of the only kidney.

Transplantation of a kidney. Experience of use of medicament for the patients who recently transferred transplantation of kidneys no.

Primary hyper aldosteronism. Patients with primary aldosteronism, as a rule, do not react to treatment by antihypertensive medicaments which mechanism of action consists in suppression system renin-angiotenzinovoy. Therefore they are not recommended to apply tablets of a lozartan.

an ischemic heart disease and cerebrovascular diseases. As well as at use of any other antihypertensive drugs, fast decrease in the ABP with an ischemic heart disease and cerebrovascular diseases can cause a myocardial infarction or a stroke in patients.

Heart failure. Patients with heart failure, a renal failure or without at use of a lozartan, as well as any other medicines operating on renin-angiotenzinovuyu a system have a risk of developing of heavy arterial hypotension and renal failure (it is very frequent — sharp). At patients with heart failure and the accompanying heavy renal failure, a heavy renal failure (the IV class on classification of NYHA) and also heart failure and cardiac arrhythmias which are followed by clinical manifestations and pose a threat for life, there is no sufficient experience of use of a lozartan. Therefore at these categories of patients lozartan it is necessary to apply with care. The combination of a lozartan with blockers of β-adrenoceptors also should be applied with care.

Stenosis of the aortal and mitral valve, subaortic hypertrophic stenosis. As well as at use of other vazodilatator, it is necessary to show extra care at patients with a stenosis of the aortal or mitral valve or a subaortic hypertrophic stenosis.

Pregnancy. Reception of antagonists of receptors of angiotensin II should not be begun during pregnancy. If continuation of therapy by antagonists of receptors of angiotensin II is not considered important, the patients planning pregnancy should be transferred to alternative antihypertensive treatment which has the approved profile of safety of use during pregnancy. If pregnancy, treatment lozartany is established it is necessary to stop immediately, and if it is possible, it is necessary to begin alternative therapy.

Other preventions and cautions. Like APF inhibitors, lozartan and other antagonists of angiotensin are less effective in decrease in the ABP at patients of negroid race in comparison with representatives of other races probably owing to the bigger number of persons with the low level of renin in this population of patients with AG.

Double blockade renin-angiotensin-aldosteronovoy (RAAS). At simultaneous use of an aliskiren and antagonists of receptors of angiotensin II or APF inhibitors the risk of arterial hypotension, a hyperpotassemia and change of function of kidneys, including OPN increases. Due to the double blockade of RAAS the simultaneous use of an aliskiren and antagonists of receptors of angiotensin II or APF inhibitors is not recommended (see INTERACTIONS). In urgent cases double blockade RAAS should control carefully function of kidneys, level of electrolytes in blood and the ABP. It is not necessary to apply at the same time antagonists of receptors of angiotensin II and APF inhibitors at patients with diabetes.

Hydrochlorothiazide. Arterial hypotension and disturbance of water and electrolytic balance. As well as at use of other means of antihypertensive therapy, at some patients the development of symptomatic hypotension is possible. Patients have to be examined for the purpose of identification of clinical signs of disturbance of water and electrolytic balance, for example a lack of liquid, a hyponatremia, a gipokhloremichesky alkalosis, a hypomagnesiemia or a hypopotassemia which can arise owing to intercurrent diarrheas or vomitings. At such patients through the corresponding periods it is necessary to carry out periodic definition of serumal electrolytes. The Dilyutsionny hyponatremia can arise at patients with hypostases in hot weather.

Metabolic and endocrine effects. Tiazida are capable to change tolerance to glucose. Correction of doses of anti-diabetic drugs, including insulin can be required. During therapy of a tiazidama the latent diabetes can be shown.

Tiazida's

can reduce excretion of calcium with urine. Tiazida can also cause slight and passing increase of level of calcium in blood serum. The expressed hypercalcemia can be symptom of the latent hyperparathyreosis. Reception of tiazid has to be stopped before carrying out a research of function of epithelial bodies.

Increase in level XC and TG can be also connected by

with therapy by diuretics of a thiazide row.

Therapy of a tiazidama can lead

to a hyperuricemia and/or gout at some patients. Because lozartan reduces the content in urine of uric acid, lozartan in a combination with a hydrochlorothiazide reduces the hyperuricemia caused by diuretic.

Liver failure. Tiazida it is necessary to apply with care at patients with an abnormal liver function or the progressing liver disease as he can cause emergence of an intra hepatic cholestasia, and minor changes of water and electrolytic balance can cause a hepatic coma. Drug is contraindicated to patients with a heavy liver failure.

Other states. At the patients receiving tiazida, allergic reactions can arise irrespective of existence in the anamnesis of allergic states or OH. It was reported about a recurrence or deteriorations in a course of a system lupus erythematosus at the patients receiving tiazida.

Special information on some excipients. Drug contains lactose. Patients with rare hereditary forms of intolerance of a galactose, deficiency of lactase or disturbance of absorption of glucose galactose should not take this drug.

Use during pregnancy or feeding by a breast

Pregnancy. It is contraindicated to apply medicine at the pregnant women or women planning pregnancy.

If the patient became pregnant, a therapy course medicament it is necessary to interrupt and begin to take other drugs.

Knows that the therapeutic dose of a combination lozartan / a hydrochlorothiazide in II and III trimester of pregnancy caused a fetotoksichnost (depression of function of kidneys, oliogidramnion (lack of water), a delay of ossification of cranial bones in a fruit) and toxic manifestations at the newborn (renal failure, arterial hypotension, a hypopotassemia).

If use of inhibitors of angiotensin II happened in the II trimester of pregnancy, it is recommended to carry out ultrasonography of function of kidneys and a skull.

Babies whose mothers accepted angiotensin II inhibitors should be controlled carefully regarding arterial hypotension, an oliguria and a hyperpotassemia (see CONTRAINDICATIONS, SPECIAL INSTRUCTIONS).

Hydrochlorothiazide. There is a limited experience of use of a hydrochlorothiazide during pregnancy, especially in the I trimester. Researches on animals are limited.

Hydrochlorothiazide gets through placentary a baryeer. On the basis of the pharmacological mechanism of action of a hydrochlorothiazide its use in II and III trimester can damage to blood supply between a placenta and a fruit and to cause in a fruit and the newborn jaundice, disorder of electrolytic balance and thrombocytopenia.

should not apply the Hydrochlorothiazide to treatment of gestational hypostasis and also gestational AG or a preeclampsia because of risk of decrease in volume of blood plasma and developing of uteroplacental hypoperfusion, without favorable action on a course of the disease.

should not apply the Hydrochlorothiazide to treatment of AG at pregnant women, except for cases when it is impossible to perform alternative treatment.

Feeding by a breast. It is not recommended to use medicament due to the lack of sufficient data on use during feeding by a breast. The patient should be transferred to alternative antihypertensive treatment which has the approved profile of safety of use during feeding by a breast, especially newborn or premature children.

Children. Experience of use of medicament for children is absent therefore lozartan/the hydrochlorothiazide should not be applied at this category of patients.

Ability to influence speed of response at control of vehicles or other mechanisms

Considering a possibility of development of such side reactions as dizziness and arterial hypotension, medicament should be used with care at control of vehicles or other mechanisms.

Interaction

Lozartan. there were messages that rifampicin and flukonazol reduce the level of an active metabolite. the clinical consequences of these interactions were not assessed.

As well as other medicaments blocking receptors of angiotensin II or their effects, the accompanying intake of kaliysberegayushchy diuretics (for example Spironolactonum, Triamterenum, amiloride), the potassium additives or salt substitutes containing potassium can lead to increase in level of potassium in blood serum. Simultaneous use is not recommended.

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As well as at use of other medicines influencing sodium removal the lithium removal can be reduced. Therefore it is necessary to control carefully lithium level in blood serum if salts of lithium apply together with antagonists of receptors of angiotensin II.

NPVP (acetylsalicylic acid in the mode of anti-inflammatory dosing, selection TsOG-2 inhibitors) and non-selective NPVP can reduce antihypertensive effect of antagonists of receptors of angiotensin II. Simultaneous use of antagonists of receptors of angiotensin II or diuretics and NPVP can lead to deterioration in function of kidneys, including possible OPN, and to increase in level of potassium in blood plasma, especially at patients with a renal failure. Such combination should be taken with caution, especially at elderly people. Ensuring adequate hydration and carrying out careful control of function of kidneys at the beginning of the accompanying therapy and periodically after it are required for patients.

accompanying reception of antagonists of receptors of angiotensin II and medicaments which suppress TsOG-2 can lead

At some patients with a renal failure to further deterioration in function of kidneys. These effects, as a rule, are reversible.

Other medicaments which can cause arterial hypotension as a basic disease or side effect are tricyclic antidepressants, neuroleptics, Baclofenum, amifostin. Simultaneous use of these medicaments can increase risk of arterial hypotension.

Research was shown that as a result of double blockade of RAAS at simultaneous use of APF inhibitors, antagonists of receptors of angiotensin II or an aliskiren the risk of side reactions, such as arterial hypotension, hyperpotassemia and changes of function of kidneys, including OPN, in comparison with use of one agent of RAAS increases (see CONTRAINDICATIONS, SPECIAL INSTRUCTIONS).

Hydrochlorothiazide. At simultaneous use the specified medicaments can interact with diuretics of a thiazide row.

Alcohol, barbiturates, medicaments or antidepressants. Orthostatic hypotension can amplify.

Antidiabetic means (oral medicaments and insulin). Use of tiazid can affect tolerance of glucose. There can be a need for change of a dose of antidiabetic means. Metformin should be applied with care as there is a risk of developing of the lactoacidosis caused by the possible functional insufficiency of kidneys connected with use of a hydrochlorothiazide.

Other antihypertensives. Hell