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Dosage form: & nbsp

Film-coated tablets.

Composition:

Core:

Active substance: zofenopril calcium - 30.0 mg (equivalent of zofenopril - 28.7 mg);

Excipients: cellulose microcrystalline - 77.2 mg, lactose monohydrate - 69.4 mg, croscarmellose sodium - 13.4 mg, magnesium stearate - 4.0 mg, silicon dioxide colloidal anhydrous - 6.0 mg.

Film Sheath: Opadrai® Y-1-7000 consisting of: hypromellose - 4.2 mg, titanium dioxide - 2.1 mg, macrogol 400 - 0.42 mg; macrogol 6000 - 1.28 mg.

Description:

Oblong film-coated tablets are white with a two-sided risk for division.

Pharmacotherapeutic group:Angiotensin converting enzyme inhibitor.
Pharmacodynamics:

Zofenopril is an antihypertensive agent from the group of angiotensin-converting enzyme (ACE) inhibitors. Zofenopril is a prodrug, as a result of the hydrolysis of the thioether bond, an active compound containing a free sulfhydryl group, zofenoprilat, is formed.

The mechanism of action of zofenoprilata in arterial hypertension and acute myocardial infarction is mainly associated with suppression of the circulating renin-angiotensin-aldosterone system, as well as with increased activity of the kallikrein-kinin system.

ACE activity in the blood plasma within 24 hours after a single oral dose of zofenopril 30 mg and 60 mg is suppressed by 53.4% ​​and 74.4%, respectively.

The result of inhibition of ACE is the reduction in the formation of angiotensin II from angiotensin I in blood plasma, which leads to a reduction in its direct vasoconstrictive effect and a decrease in the secretion of aldosterone.

Under the action of zofenoprilata, as well as other ACE inhibitors, vascular dilatation occurs, which leads to a decrease in the total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preloads on the myocardium. Reducing the concentration of angiotensin II in the blood plasma leads to a slowing of the process of myocardial remodeling, which can negatively affect the prognosis in acute myocardial infarction.

As a result of inhibition of ACE, the activity of the circulating and local kallikrein-kinin system also increases, which promotes peripheral vasodilation by activation of the prostaglandin system.

In patients with arterial hypertension, the use of zofenopril leads to a decrease in blood pressure in the "lying" and "standing" positions approximately in the same degree, without a reflex increase in the heart rate.

The antihypertensive effect of zofenoprilat is more pronounced with high renin activity of blood plasma than with normal or decreased.

A stable antihypertensive effect is achieved with prolonged therapy with zofenopril. Thus, for some patients, several weeks of continuous therapy are required to achieve optimal BP reduction.

In patients with anterior myocardial infarction who did not receive thrombolytic therapy, zofenopril is used to improve survival and reduce the incidence of severe heart failure.

A randomized placebo-controlled clinical trial of zofenopril was conducted with the participation of 1556 patients who underwent anterior myocardial infarction and who did not receive thrombolytic therapy. The use of zofenopril began within 24 hours of the development of myocardial infarction and lasted for 6 weeks. The incidence of primary combined endpoint (development of severe heart failure and / or death within 6 weeks) was lower in the zofenopril group (zofenopril 7.1%, placebo 10.6%). Within one year, survival in patients in the zofenopril group was higher than in the placebo group.

Pharmacokinetics:

Absorption. After oral administration zofenopril quickly and completely absorbed from the gastrointestinal tract (GIT). In organism zofenopril is almost completely converted to zofenoprilat, which has a pronounced pharmacological activity. The maximum concentration (Cmax) zofenoprilata in the blood plasma is achieved after 1.5 hours after ingestion of a single dose. The pharmacokinetics of a single-dose dose of zofenopril is linear in the range of 10-80 mg. After taking zofenopril in a daily dose of 15-60 mg for 3 weeks, cumulation does not occur. Simultaneous food intake reduces the rate, but not the full absorption of zofenopril. The area under the concentration-time curve (AUC) of zofenoprilat before and after meals is almost identical.

Distribution. Approximately 88% of zofenopril binds to plasma proteins. The volume of distribution (Vd) in the saturation stage is 96 liters.

Metabolism. The main metabolite is zofenoprilat (22%), metabolized in various ways: conjugation with glucuronic acid (17%), cyclization and conjugation with glucuronic acid (13%), conjugation with cysteine ​​(9%) and S-methylation of thiol group (8%) .

Excretion. Zofenopril after oral administration is excreted by the kidneys (69%) and through the intestine (26%). After oral administration of zofenopril, the elimination half-life (T1/2) zofenoprilata is 5.5 h, and its total clearance is 1300 ml / min.

Pharmacokinetics in renal failure

In patients with mild renal insufficiency (creatinine clearance> 45 mL / min and <90 mL / min) zofenopril is excreted from the body at the same rate as in healthy volunteers (creatinine clearance> 90 ml / min). Patients in this group do not need dose adjustment.

In patients with moderate to severe renal insufficiency (creatinine clearance 7-44 ml / min), the rate of excretion is reduced to approximately 50% compared to that of healthy volunteers. Therefore, patients in this group should be given ½ of the recommended dose of zofenopril.

In patients with terminal end-stage renal failure who are on hemodialysis or peritoneal dialysis, the elimination rate is reduced to 25% of the values ​​in healthy volunteers. Patients in this group should be given ¼ of the recommended dose of zofenopril.

Pharmacokinetics in liver failure

In patients with hepatic insufficiency of mild or moderate severity (less than 9 on the Child-Pugh scale) with a single dose of zofenopril with a radioactive label, the value of Cmax and time to reach the maximum concentration (TCmax) for zofenoprilat coincided with those of healthy volunteers. However, the AUC values ​​in patients with cirrhosis were twice as high as in healthy volunteers. Thus, patients with hepatic insufficiency of mild to moderate severity should be given ½ of the recommended initial dose of zofenopril.

In patients with hepatic insufficiency of severe severity (more than 9 on the Child-Pugh scale), there are no data on the pharmacokinetics of zofenopril and zofenoprilat, therefore zofenopril is contraindicated in patients of this group.

Indications:

Arterial hypertension of mild and moderate (I-II) severity.

Acute myocardial infarction (starting from the first 24 hours) in patients with stable hemodynamic parameters and not receiving thrombolytic therapy, including in patients with symptoms of heart failure.

Contraindications:

  • increased sensitivity to zofenopril or other ACE inhibitors, as well as to other components of the drug;
  • angioedema in history, associated with the use of ACE inhibitors;
  • hereditary / idiopathic angioedema;
  • hepatic failure of severe severity (more than 9 on the Child-Pugh scale);
  • bilateral stenosis of the renal arteries or stenosis of the renal artery of the only kidney (risk of developing kidney failure);
  • condition after kidney transplantation (no experience with the drug);
  • primary aldosteronism;
  • hereditary lactose intolerance, lactase deficiency or glucose malabsorption syndrome and lactose;
  • age to 18 years (efficiency and safety ns established);
  • pregnancy, the period of breastfeeding;
  • use in women of childbearing age not using effective contraception;
  • simultaneous dialysis using high-throughput polyacrylonitrile membranes (eg AN69 *) or low-density lipoprotein plasmapheresis (LDL-apheresis);
  • simultaneous application with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate less than 60 ml / min / 1.73 m2).

Carefully:

  • Renovascular hypertension, unilateral renal artery stenosis;
  • angioedema in history, not associated with ACE;
  • chronic renal failure;
  • hepatic insufficiency of mild to moderate severity (less than 9 on the Child-Pugh scale);
  • chronic heart failure (CHF) III-IV functional class according to the NYHA classification;
  • cerebrovascular diseases;
  • aortic stenosis, mitral stenosis, disturbed outflow of blood from the left ventricle, hypertrophic obstructive cardiomyopathy;
  • diabetes;
  • psoriasis;
  • systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma);
  • hyperkalemia;
  • age over 75 years;
  • simultaneous desensitizing therapy;
  • with surgical interventions / general anesthesia;
  • conditions, accompanied by a decrease in the volume of circulating blood (BCC) (as a result of diuretic therapy, with restriction of consumption of table salt, hemodialysis, diarrhea and vomiting);
  • the use of Negroid race in patients.

Pregnancy and lactation:

The use of 3ocardis® 30 during pregnancy is contraindicated.

When planning or diagnosing pregnancy, Zokardis® 30 should be discontinued and hypotensive drugs of another group with a confirmed safety profile should be prescribed for use in pregnant women.

With the use of ACE inhibitors in the II and III trimesters of pregnancy, fetotoxicity (impairment of fetal kidney function, low blood pressure, slowing ossification of the fetal bones) is possible, and in newborns, kidney failure, arterial hypotension and hyperkalemia. Therefore, for newborns whose mothers took the preparation of 3ocardis® 30 during pregnancy, careful observation is needed to determine whether these symptoms may be developing.

If it is not possible to cancel Zokardis® 30 during pregnancy, careful monitoring of the fetal kidney function and skull bones with ultrasound should be performed.

Information on the use of Zokardis® 30 during breastfeeding is not available, so its use in women during breast-feeding is contraindicated.

Dosing and Administration:

Inside. Tablets are taken regardless of the meal, without chewing, squeezed with enough liquid.

To select the optimal dosage regimen, it is advisable to use the most suitable form of the drug release - Zokardis® 7,5 or Zokardis® 30, containing 7.5 mg or 30 mg of zofenopril calcium, respectively.

Arterial hypertension

The drug is used in both monotherapy and in combination with other antihypertensive drugs.

The initial dose is ½ tablets of Zokardis® 30 (15 mg of zofenopril calcium) once a day.

The need to increase the dose of the drug is determined by measuring blood pressure immediately before taking the next dose. Antihypertensive effect develops within several weeks, therefore it is recommended to increase the dose of the drug at an interval of four weeks.

Usually, the maintenance dose is 1 tablet of Zokardis® 30 (30 mg of zofenopril calcium) once a day.

The maximum daily dose is 2 tablets of Zokardis® 30 (60 mg of zofenopril calcium) per day, taken once or divided into two doses.

Patients, taking diuretics, 2-3 days prior to the start of the use of the drug Zokardis® 30, it is necessary to temporarily discontinue the use of diuretics. The use of Zokardis® 30 should be started with ½ tablets of Zokardis® 30 (15 mg of zofenopril calcium) once a day. If diuretics can not be canceled, then therapy should be started with 1 tablet of Zokardis® 7.5 (7.5 mg of zofenopril calcium) per day.

Patients older than 75 years

In patients older than 75 years with a creatinine clearance> 45 ml / min, dose adjustment is not required. In patients older than 75 years with creatinine clearance <45 mL / min, the use of ½ from the dose recommended to patients without renal failure.

Creatinine clearance (ml / min) = ((140-age) x body weight (kg)) / (conc. creatinine in plasma (mg / dl) x 72)

The above formula allows you to calculate the clearance of creatinine in men. For women, the obtained value should be multiplied by 0.85.

Patients with renal insufficiency or who are on hemodialysis

In patients with mild renal insufficiency (creatinine clearance> 45 ml / min), dose adjustment is not required.

Patients with moderate to severe renal insufficiency (creatinine clearance <45 mL / min) should be administered ½ of the dose recommended to patients without renal failure.

The dose of the drug for patients on hemodialysis is ¼ of the dose recommended to patients without renal failure.

Patients with hepatic insufficiency

In patients with mild to moderate hepatic insufficiency (less than 9 on the Child-Pugh scale), the initial dose of Zokardis® 30 is ½ the dose recommended for patients without hepatic insufficiency.

In patients with hepatic insufficiency of severe severity (more than 9 on the Child-Pugh scale), the use of Zokardis® 30 is contraindicated.

Acute myocardial infarction (as part of combination therapy)

Treatment with Zokardis® 30 should be started within the first 24 hours after the onset of the first symptoms of myocardial infarction and continued for 6 weeks.

The following scheme of application is recommended:

1 st and 2 nd day: 1 tab. preparation Zokardis® 7.5 (7.5 mg zofenopril calcium) every 12 hours;

3rd and 4th day: ½ table. preparation Zokardis® 30 (15 mg of zofenopril calcium) every 12 hours;

from the 5th day onwards: 1 tab. Preparation Zokardis * 30 (30 mg of zofenopril calcium) every 12 hours.

With low systolic blood pressure (SBP) (<120 mm Hg.v.) for the first sin days after myocardial infarction, the daily dose Zokardis® 30 should not be increased. In the case of arterial hypotension (SBP <100 mmHg. V.) Treatment may be continued at a dose that was well tolerated previously. In case of severe hypotension (SBP <90 mmHg. V. On two consecutive measurements at intervals of not less than one hour) using the product Zokardis® 30 should be stopped.

In the case of persistent signs of left ventricular dysfunction or heart failure, myocardial symptoms after 6 weeks after myocardial infarction, as well as the concomitant hypertension drug application Zokardis® 30 may be continued for a long time.

Simultaneously shall apply standard treatments recommended in acute myocardial infarction (including nitrates, acetyl salicylic acid as antiplatelet drugs, beta-blockers).

Patients older than 75 years

30 Zokardis® drug should be used with caution in patients older than 75 years with acute myocardial infarction.

Patients with renal insufficiency or those on dialysis

The efficacy and safety of Zokardis® 30 in patients with acute myocardial infarction and renal insufficiency (at a serum creatinine concentration of> 2.1 mg / dL and a proteinuria value of> 500 mg / day) or those on dialysis are not established. Therefore, in this category of patients the drug Zokardis® 30 should not be used.

Patients with hepatic insufficiency

The efficacy and safety of Zokardis® 30 in patients with acute myocardial infarction and liver failure have not been established. Therefore, in this category of patients the drug Zokardis®30 should not be used.

Side effects:

Possible side effects are given below in accordance with WHO classification in the descending incidence of the event: very often (≥ 1/10), often (≥ 1/100, <1/10) infrequently (≥ 1/1000, <1/100) , rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), the frequency is not established (estimates are not available from available data).

Violations of the blood and lymphatic system

Frequency not set: thrombocytopenia, leukopenia, agranulocytosis, pancytopenia,hemolytic anemia in patients with deficiency of glucose-6-phosphate dehydrogenase, a decrease or decrease in hemoglobin, a decrease in hematocrit.

Disorders from the metabolism and nutrition

Rarely: hypoglycemia.

Disorders of the psyche

Rarely: depression, mood lability, sleep disorders, confusion.

Disturbances from the nervous system

Often: dizziness, headache;

Frequency not set: paresthesia, dysgeusia (a violation of taste perception), imbalance.

Disturbances on the part of the organ of sight

Rarely: blurred vision.

Violations of the hearing and vestibular organs

Rarely: sensation of ringing in the ears.

Disorders from the cardiovascular system

Rarely: "tides" of blood to the face;

Frequency not set: tachycardia, palpitations, arrhythmias, angina pectoris, acute myocardial infarction; a marked decrease in blood pressure at the initial stage of therapy and with an increase in the dose (simultaneously with arterial hypotension, symptoms such as dizziness, weakness, visual impairment, and occasionally a violation of consciousness (syncope) can be observed).

Disturbances from the respiratory, thoracic and mediastinal organs

Often: cough;

Rarely: shortness of breath, sinusitis, rhinitis, glossitis, bronchitis, bronchospasm;

Frequency not set: angioedema with involvement of the face and oropharyngeal zone, including, with obstruction of the respiratory tract.

Disorders from the digestive system

Often: nausea, vomiting;

Rarely: intestinal angioedema;

Frequency not set: abdominal pain, diarrhea, constipation, dry mouth; pancreatitis, intestinal obstruction.

Disturbances from the liver and bile ducts

Frequency not set: cholestatic jaundice, hepatitis.

Disturbances from the skin and subcutaneous tissues

Infrequently: skin rash;

Rarely: angioedema, hyperhidrosis.

Frequency not set: allergic reactions and hypersensitivity reactions, such as pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, psoriasis-like rashes, alopecia (reactions may be accompanied by fever, muscle pain, eosinophilia, and titer of antinuclear antibodies).

Disturbances from the skeletal muscles and connective tissue

Infrequently: muscle cramps;

Frequency not set: myalgia.

Disorders from the kidneys and urinary tract

Rarely: disturbances of urination;

Frequency not set: impaired kidney function, progression of renal failure; acute renal failure.

Violations of the genitals and mammary glands

Rarely: erectile disfunction.

Other

Often: increased fatigue;

Infrequently: asthenia;

Rarely: peripheral edema, pain in the chest.

Laboratory indicators

Frequency not set: an increase in the concentration of urea and creatinine in the blood plasma; an increase in the activity of "hepatic" enzymes, an increase in the concentration of bilirubin in the blood plasma.

With simultaneous use of ACE inhibitors and preparations of gold care should be taken in connection with the possibility of developing "nitrate-like" reactions (symptoms of vasodilation, including "hot flushes" to the face, nausea, dizziness and arterial hypotension, which can be very difficult).

Overdose:

Symptoms: pronounced BP reduction, shock, stupor, bradycardia, water-electrolyte balance disorders, renal failure.

Treatment: In case of an overdose, the patient should be under close medical supervision, preferably in the intensive care unit. Constant monitoring of the electrolytes and creatinine in the blood plasma is shown.

The tactics of the therapy depends on the prescription period of the overdose, the severity of the prevailing symptoms and the degree of their severity. In the case of a relatively recent administration of the drug, gastric lavage, the appointment of adsorbents and the intake of sodium sulfate solution are shown; in more severe cases, the patient is transferred to a horizontal position with a low head and carry out activities aimed at stabilizing blood pressure: intravenous administration of 0.9% sodium chloride solution or plasma substitutes, if necessary - hemodialysis (polyacrylonitrile membranes with high capacity should be avoided).

With the development of a stable bradycardia or pronounced vagal reactions, the use of atropine is indicated.If the therapy is ineffective, consider setting up an artificial pacemaker.

Interaction:

Do not use concurrently

It is not recommended to use the potassium-sparing diuretics (spironolactone, eplerenone, triamterene or amiloride), potassium-containing drugs or food additives because of the risk of developing hyperkalemia.

If, due to established hypokalemia, the simultaneous use of the above-mentioned drugs with zofenopril is indicated, they should be used with caution under the control of the electrocardiogram (ECG) and the potassium content in the blood plasma.

Clinical studies show that the double blockade of the renin-angiotensin-aldosterone system (RAAS) with simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren, is associated with a higher incidence of side effects such as hypotension, hyperkalemia, and decreased kidney function (including acute renal failure) than with only one drug that affects RAAS.Thus, simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended.

The simultaneous use of zofenopril and preparations containing aliskiren, contraindicated in patients with diabetes mellitus and renal insufficiency (at a glomerular filtration rate <60 ml / min / 1.73 m2).

Patients with diabetic nephropathy should not simultaneously use ACE inhibitors and antagonists of angiotensin II receptors.

In the case when the simultaneous use of two agents that affect the RAAS is necessary, their application should be carried out under the supervision of a physician and with regular monitoring of renal function, blood pressure and electrolyte levels in blood plasma. The simultaneous use of zofenopril and lithium preparations is not recommended because of the risk of developing lithium intoxication. The simultaneous use of thiazide diuretics with lithium preparations may increase the likelihood of developing lithium intoxication and enhance the already existing risk against the background of the use of ACE. If this combination is used, regular monitoring of the lithium concentration in the blood plasma is necessary.

Use with caution at the same time

Care should be taken when using thiazide and "loop" diuretics. Prior treatment with diuretics may lead to a decrease in the BCC and promote the development of dehydration and hypotension in the initial stages of the drug Zokardis® 30. Hypotensive effects of the drug can be reduced by eliminating the use of diuretics, increased fluid intake, or salt or initiate treatment with zofenopril application of lower doses.

Before starting the use of Zokardis® 30, it is necessary to temporarily discontinue the use of diuretics. Regular monitoring of kidney function during the first few weeks of therapy is required.

This approach also applies to patients with angina or cerebrovascular disease in which excessive lowering of blood pressure can lead to acute myocardial infarction or cerebrovascular accident.

In case of development of arterial hypotension, the patient should be placed on his back. You may need intravenous injection of 0.9% sodium chloride solution to replenish the BCC.The development of arterial hypotension after taking the first dose does not exclude further use of the drug, provided a cautious dose titration.

ACE inhibitors can enhance the antihypertensive effect of some general anesthetics.

When used simultaneously with narcotic analgesics, tricyclic antidepressants, neuroleptics and barbiturates may develop orthostatic hypotension.

When used simultaneously with other antihypertensive agents (alpha and beta-adrenoblockers, blockers of "slow" calcium channels) antihypertensive effect can be potentiated.

Care should be taken when using nitrates and / or other vasodilators simultaneously.

Simultaneous application cyclosporine with ACE inhibitors increases the risk of developing renal dysfunction.

With simultaneous application allopurinol, procainamide, cytostatics, glucocorticosteroids and immunosuppressants with ACE inhibitors the risk of developing hypersensitivity reactions and leukopenia increases.

In rare cases, ACE inhibitors can increase the hypoglycemic action of insulin and hypoglycemic agents for oral administration (eg, sulfonylureas) in patients with diabetes mellitus.In these cases, a reduction in the dose of hypoglycemic agent for ingestion and / or insulin may be required.

Sympathomimetics can attenuate the antihypertensive effect of ACE inhibitors.

When used simultaneously with antacids a decrease in the bioavailability of ACE inhibitors is possible.

With simultaneous use of ACE inhibitors and preparations of gold care should be taken in connection with the possibility of developing "nitrate-like" reactions (symptoms of vasodilation, including "hot flushes" to the face, nausea, dizziness and arterial hypotension, which can be very difficult).

Cimetidine can enhance the antihypertensive effect of zofenopril.

It should be taken into account when applying simultaneously

When used simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2) and acetylsalicylic acid in a fraction> 3 g / day, it is possible to reduce the antihypertensive effect of ACE inhibitors, including zofenopril. Also, with the simultaneous use of NSAIDs and ACE inhibitors, it is possible to increase the potassium content in the blood plasma against a background of decreased kidney function.These changes are usually reversible and occur mainly in patients with impaired renal function. In rare cases, development of acute renal failure is possible, especially in patients with impaired renal function, for example, in elderly or dehydrated patients.

Clinical data on the direct interaction of zofenopril with other drugs that are metabolized by isoenzymes of the cytochrome P450 system are not available. However, studies in vitro demonstrated the absence of a potentially possible interaction with drugs that are metabolized with the participation of cytochrome P450 isoenzymes.

Special instructions:

As with other ACE inhibitors, one should keep in mind the likelihood of developing symptomatic arterial hypotension (even a few hours after taking the first dose of the drug), especially in patients with severe heart failure with or without kidney function, and in patients with disturbances of water-electrolyte balance, conditioned by previous therapy with diuretics, diet with restriction of table salt, diarrhea, vomiting, on hemodialysis and in severe renin-dependent arterial hypertension ii.

In patients with IHD, cerebrovascular disease, a significant reduction in blood pressure can lead to the development of acute myocardial infarction and / or stroke.

In patients at risk for developing symptomatic arterial hypotension, treatment should be started under close medical supervision, preferably in a hospital setting, starting at lower doses and then following a careful dose titration.

In some patients with heart failure with normal or low blood pressure, the use of Zokardis® 30 can cause an additional reduction in blood pressure. This effect is predictable and usually does not serve as a reason for cancellation of treatment. If excessive arterial hypotension in the patient persists, a dose reduction or withdrawal of the Zokardis® 30 drug may be required.

In patients with acute myocardial infarction with the risk of severe hemodynamic disorders due to the use of vasodilating agents (patients with systolic blood pressure <100 mm Hg, cardiogenic shock) therapy with Zokardis® 30 should not be started, ego can lead to the development of severe arterial hypotension.In the case of persistent arterial hypotension (systolic BP <90 mm Hg for more than one hour), the use of Zokardis® 30 should be discontinued. In the development of severe heart failure after acute myocardial infarction, Zokardis® 30 should be used only in patients with stable hemodynamic parameters.

There is an increased risk of severe hypotension and renal insufficiency with the use of ACE inhibitors in patients with renovascular hypertension and / or bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney. In patients in this group, the use of Zokardis® 30 is contraindicated.

In patients with unilateral stenosis of the renal artery, renal failure may be accompanied by only small changes in the concentration of creatinine in the blood plasma. Therapy with Zokardis® 30 in patients in this group should start with small doses in a hospital setting under close medical supervision. The subsequent increase in the dose should be done with caution, under the control of the concentration of creatinine in the blood plasma.

In patients with renal insufficiency, Zokardis® 30 should be used with caution, therapy should be started with smaller doses and regular monitoring of kidney function. Renal failure was reported in the appointment of ACE inhibitors, mainly in patients with severe heart failure or kidney disease, including renal artery stenosis. In some patients without signs of kidney pathology, there was an increase in the concentration of urea and creatinine in the blood plasma, especially with the simultaneous use of diuretics. You may need to reduce the dose of an ACE inhibitor and / or stop using a diuretic. During the first few weeks of therapy, regular monitoring of kidney function is recommended. Proteinuria can occur, in particular, in patients with impaired renal function or taking relatively high doses of ACE inhibitors. Patients with a history of renal disease need to determine the protein content in the urine (the use of test strips to study the first morning dose of urine) before and periodically after treatment.Anaphylactoid reactions such as face swelling, blood flushes to the face, arterial hypotension and shortness of breath during the first minutes of hemodialysis were observed with the use of ACE inhibitors in dialysis using polyacrylonitrile membranes of high throughput (eg AN69®). Therefore, for such patients it is recommended either the use of dialysis membranes of a different type, or the use of antihypertensive drugs of another group.

There is evidence that patients receiving ACE inhibitors with LDL-apheresis (low-density lipoprotein plasmapheresis) with dextran sulfate have a high incidence of anaphylactoid reactions similar to those found in patients undergoing hemodialysis using membranes with high capacity. If LDL-apheresis is performed, ACE inhibitors should be temporarily replaced with antihypertensive drugs from another group.

There have been reports of the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors concomitantly with the procedure for desensitization (for example, the Hepatoptera (Heminoptera)) or after insect bites.Such reactions can be avoided if the use of ACE inhibitors is temporarily stopped before desensitization begins. However, they can develop again when the drug is given again. ACE inhibitors should be used with caution in patients who undergo such desensitization and in patients receiving immunotherapy with bee venom.

It is reported the appearance of cough in the treatment with ACE inhibitors. Usually, cough is unproductive and stops after the drug is discontinued. Cough due to treatment with ACE inhibitors should be taken into account in the differential diagnosis of cough.

Rarely with the treatment with ACE inhibitors, there is a syndrome that starts with cholestatic jaundice, which progresses up to fulminant necrosis and, in some cases, leads to a legal outcome. The mechanism of development of this syndrome is unclear. Patients who have jaundice and / or a marked increase in hepatic enzyme activity when ACE inhibitor treatment is treated should immediately discontinue the use of ACE inhibitors and provide medical supervision.

In some patients taking ACE inhibitors, including, the drug Zokardis® 30, there is an increase in potassium in the blood plasma.The risk group for hyperkalemia includes patients suffering from renal insufficiency and / or diabetes mellitus taking potassium-sparing diuretics or potassium-containing substitutes for edible salt, other drugs that increase the potassium content in the blood plasma (eg, heparin). If the use of the above medicines against the background of treatment with Zokardis® 30 is necessary, regular monitoring of the potassium content in the blood plasma is recommended.

In extensive surgical procedures with general anesthesia, ACE inhibitors can induce arterial hypotension until the development of shock, since the formation of angiotensin II can be blocked by the compensatory release of renin. If the use of Zokardis® 30 is deemed necessary, then the BCC should be carefully monitored when carrying out the above measures. Before surgical interventions (including dental procedures), the surgeon / anesthesiologist should be alerted to the patient's use of Zokardis® 30. Neutropenia, agranulocytosis, thrombocytopenia, anemia may develop with ACE inhibitor therapy.With the normal function of the nights and the absence of other complications, neutropenia occurs rarely. This condition can develop in patients with impaired renal function, especially if the patient has systemic connective tissue diseases (eg, systemic lupus erythematosus, scleroderma), during immunosuppressive therapy, in cases of concomitant use of allopurinol or procainamide, as well as a combination of all of the above factors. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. If Zokardis ® 30 is still used in such patients, regular monitoring of the number of leukocytes in the blood (in the first 3 months of treatment - every 2 weeks, and further - regular monitoring) is recommended, and during treatment all patients should be instructed about the need to inform the doctor about any signs of development of a possible infection (eg, sore throat, fever), in which the study of the leukocyte formula is shown. If neutropenia or a suspected neutropenia is detected (neutrophil count less than 1000 / mm3) the preparation Zokardis® 30 and other concomitant medications should be discontinued. These changes are reversible. After the withdrawal of the ACE inhibitor, the amount of neutrophils reaches the initial level.

In patients with diabetes mellitus receiving hypoglycemic agents for ingestion and / or insulin, the concentration of glucose in the blood plasma must be carefully monitored during the first month of treatment with Zokardis® 30.

Reports of angioedema (angioedema) of the face, limbs, lips, tongue, vocal folds and / or larynx have been reported in patients who received ACE inhibitors at different periods of treatment. In such cases, treatment with Zokardis® 30 should be discontinued immediately, an antihypertensive drug from another group should be prescribed, and appropriate medical supervision of the patient should be established until the symptoms disappear completely. The patient should be placed in a hospital for medical observation for a period of at least 12-24 hours, and not discharged from the hospital until the symptoms have completely disappeared. Even in those cases where only the difficulty of swallowing is disturbed without difficulty in breathing,patients should be under medical supervision for a long time, since therapy with antihistamines and corticosteroids may not be sufficient. Angioedema of the larynx or tongue can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction; appropriate therapy should be performed in the shortest possible time and include immediate subcutaneous administration of a 0.1% solution of epinephrine (0.3-0.5 ml) or a slow intravenous injection of a 1 mg / ml adrenaline solution diluted according to the instructions for use, ECG and blood pressure monitoring, as well as measures to ensure airway patency. Patients with an angioedema edema of another etiology in the history of taking ACE inhibitors are at increased risk for the development of this pathology.

In patients of the Negroid race, the frequency of angioedema development with ACE inhibitors is higher than in representatives of other races.

Similar to other ACE inhibitors, the Zokardis® 30 preparation may be less effective in reducing blood pressure in members of the Negroid race than in individuals of other races,due to the low level of renin in patients with hypertension in this population. This difference can be eliminated by the addition of diuretics.

The drug contains lactose, so its use in patients with hereditary intolerance to galactose, a deficiency of lactase and a syndrome of malabsorption of glucose and galactose is contraindicated.

During the period of application of the drug Zokardis * 30 it is not recommended to drink alcoholic beverages. alcohol increases the antihypertensive effect of the drug.

Effect on the ability to drive transp. cf. and fur:

During the treatment with Zokardis® 30, care should be taken when driving vehicles and other mechanisms, engaging in potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions (as possible the development of side effects such as drowsiness, fatigue and dizziness ).

Form release / dosage:

Tablets, film-coated, 30 mg.

Packaging:

For 7 or 14 tablets in a contour squeeze box (blister) made of PVC / PVDC / aluminum foil.

For 1 or 2 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep the medicine out of the reach of children!

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription
Registration number:LS-000777
Date of registration:23.08.2010
The owner of the registration certificate:Berlin-Chemie / Menarini Pharma, GmbH Berlin-Chemie / Menarini Pharma, GmbH Germany
Manufacturer: & nbsp
Information update date: & nbsp08.09.2015
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