Zokardis® 28's 7.5 mg coated tablets
- $15.70
The instruction for medical use
of medicine Зокардис® 7.5 Зокардис® 30
the Trade name
Зокардис® 7.5 Зокардис® 30
International unlicensed
name Zofenopril Lekarstvennaya
the Tablet form film coated 7.5 mg and 30 mg
Structure
One tablet contains
active agent: 7.5 mg and 30 mg of a zofenopril of calcium that there correspond
7.2 mg and 28.7 mg of a zofenopril
excipients: microcrystalline cellulose, lactoses monohydrate, starch corn, magnesium stearate, silicon dioxide colloidal anhydrous
structure of a cover:
a gipromelloza, the titan dioxide (E 171), a macrogoal 400, a macrogoal 6000
Description
of Зокардис® 7.5 mg
of the Tablet of round shape, with a biconvex surface, film coated white
Зокардис® 30 color of mg
of a tablet of oblong shape, film coated white color, with risky on both parties. The tablet can be divided into two identical parts.
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotenzinkonvertiruyushchy enzyme (AKF) inhibitors. Zofenopril.
The ATX C09AA15 code
the Pharmacological
Zofenopril Pharmacokinetics properties of calcium is pro-medicine as active inhibitor is free sulfhydryl connection — zofenoprilat — received by thioradio hydrolysis.
Absorption
Zofenopril of calcium is quickly and completely absorbed at oral administration and is exposed to almost full transformation in zofenoprilat which maximum concentration in blood is reached in 1.5 hours after reception of an oral dose of Zokardisa®. The kinetics of a single dose is linear in the range of doses of 10-80 mg of a zofenopril of calcium. After use of 15-60 mg of a zofenopril of calcium within 3 weeks the accumulation is not observed. Presence of food at digestive tract reduces speed, but not extent of absorption, but the areas under curve (AUC) of the zofenoprilat are almost identical being able on an empty stomach and after a meal.
Distribution
About 88% of the circulating radioactivity measured by ex-Vivo after reception of a dose of a zofenopril of calcium marked radioactive isotope, contacts protein of plasma, and the established volume of distribution is 96 liters.
Metabolism
In urine of the person after reception of a dose of a zofenopril of calcium, marked radioactive isotope identified eight metabolites making 76% of radioactivity of urine. The main metabolite is zofenoprilat (22%) which then is metabolized in several ways, including conjugation with glucuronic acid (17%), cyclization and conjugation with glucuronic acid (13%), conjugation with cysteine (9%) and S-methylation of thiol group (8%). After oral administration of a zofenopril of calcium the elimination half-life of the zofenoprilat makes 5.5 hours, and its general clearance - 1300 ml/min.
Removal
Marked radioactive isotope zofenoprilat, entered intravenously, is removed with urine (76%) and a stake (16%), and after peroral marked radioactive isotope of a dose of a zofenopril of calcium in urine and Calais 69% and 26% of radioactivity respectively are found that demonstrates existence of two ways of elimination - kidneys and a liver.
The pharmacokinetics
At normal renal function at elderly patients of dose adjustment is not required from elderly patients.
Pharmacokinetics in renal dysfunction
based on comparison of key pharmacokinetic parameters of the zofenoprilat which assessment was carried out after oral administration of a zofenopril of calcium marked radioactive isotope, it is revealed that at patients with a renal failure of easy degree (clearance of creatinine & gt, 45 and & lt, 90 ml/min.) zofenoprit it is brought out of an organism with the same speed, as at patients with normal renal function (clearance of creatinine & gt, 90 ml/min.).
At patients with a renal failure of average and heavy degree (7 - 44 ml/min.) the speed of elimination is reduced, approximately, to 50% of normal. It indicates that this group of patients should appoint a half of a usual initial dose of Zokardisa®.
Patients in an end-stage have diseases of the kidneys which are on a hemodialysis and peritoneal dialysis, the speed of elimination is reduced to 25% of normal. It indicates that this group of patients should appoint a quarter of a usual initial dose of Zokardisa®.
Pharmacokinetics in liver dysfunction
At patients with dysfunction of a liver easy or moderate severity which were given a single dose of a zofenopril of calcium marked radioactive isotope, values of Tmaks and Smaks for the zofenoprilat were similar to the values received at healthy patients. However PPK values (the areas under a curve, AUC) at patients with cirrhosis were approximately twice more in comparison with PPK values at normal patients, indicating that patients with dysfunction of a liver easy or moderate severity should appoint a half of an initial dose of Zokardisa® appointed to patients with normal function of a liver.
Data on pharmacokinetics of a zofenopril and the zofenoprilat at patients with dysfunction of a liver of heavy degree are absent therefore to these patients zofenoprit is contraindicated.
The pharmacodynamics
Favorable action of Zokardisa® in cases of arterial hypertension and acute myocardial infarction is result, mainly, of suppression plasmatic system renin-angiotensin-aldosteronovoy. Result of inhibition of APF (Ki of 0.4 nanometers in lungs of a rabbit for argininovy salt of the zofenoprilat) is decrease in level of angiotensin II in blood plasma which leads to decrease in vasoconstrictive activity and to hyposecretion of Aldosteronum. In spite of the fact that this decrease is rather small, along with loss of sodium and liquid perhaps some increase in potassium concentration in blood serum. On secretion of renin the increase in activity of plasma renin is result of the termination of negative feedback of angiotensin II.
The activity of plasma APF within 24 hours after single dose of a zofenopril of calcium in a dose of 30 mg and 60 mg is suppressed respectively for 53.4% and 74.4%.
As a result of inhibition of APF the activity of the circulating and local kallikrein-kinin system which promotes a peripheral vazodilatation by activation of a prostaglandinovy system increases. It is possible that the hypotensive effect of a zofenopril of calcium is connected with this mechanism which is perhaps, one of the causes of side effects.
At patients with arterial hypertension the use of Zokardisa® leads to a lowering of arterial pressure in a prone position and standing approximately to the same extent with lack of compensatory increase in heart rate. Average system vascular resistance after use of Zokardisa® tends to reduction.
From some patients the achievement of an optimum lowering of arterial pressure requires several weeks of therapy. The stable hypotensive effect is reached by long therapy.
Sudden interruption of therapy was not connected with sharp increase in arterial blood pressure. Now the actions of Zokardisa® given relatively on incidence and mortality of the patients having arterial hypertension no.
Though manifestation of hypotensive action was observed at persons of all studied races, nevertheless reaction of an organism at the patients of negroid race having arterial hypertension (usually it is populations in which the lowrenine form of arterial hypertension is observed) on monotherapy by APF inhibitor on average is less expressed than at patients of other races. At additional therapy by diuretics this difference is not observed.
The clinical effect reached as a result of timely use of Zokardisa® in a myocardial infarction can be connected with many factors, such as decrease in level of angiotensin II in plasma (i.e. suppression of process of remodeling of ventricles which can negatively influence the forecast in case of a heart attack) and increase in concentration of dilators in plasma and cells (prostaglandin - a kinin system).
Randomized placebo - controlled clinical trial of a zofenopril is carried out with participation of 1556 patients a myocardial infarction of a front wall who were not exposed to thrombolytic therapy. Treatment was begun within 24 hours and continued for 6 weeks. Frequency of primary combined final point (heavy heart failure and/or death within 6 weeks) was reduced at patients who were treated zofenoprily (zofenoprit 7.1%, placebo of 10.6%). Within one year the survival rate in group of the patients accepting Zokardis® was higher, than in group of not accepting Zokardis®.
Combined use of APF inhibitors and blockers of receptors of angiotensin II was investigated in two large-scale, randomized, controlled studies (ONTARGET (ONgoing Telmisartan Alone and in a combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)).
ONTARGET represented the research conducted at patients with a cardiovascular or cerebrovascular disease in the anamnesis or the diabetes 2 types which is followed by signs of damage of a target organ. VA NEPHRON-D represented the research conducted at patients with diabetes 2 types and a diabetic nephropathy. These researches did not reveal significant favorable impact on an outcome of renal and/or cardiovascular diseases and on mortality from them while in comparison with monotherapy the increased risk of development of a hyperpotassemia, acute damage of kidneys and/or hypotonias took place. Considering similarity of pharmakodinamichesky properties, these results are also applicable for other APF inhibitors and blockers of receptors of angiotensin II.
Combined use of APF inhibitors and blockers of receptors of angiotensin II contraindicated at patients with a diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) represented the research conducted for identification of positive effect from addition of an aliskiren to standard therapy by APF inhibitors or blockers of receptors of angiotensin II at patients with diabetes 2 types and a chronic disease of kidneys, a cardiovascular disease, or having both diseases. This research was interrupted in connection with the increased risk of undesirable outcomes earlier. Cardiovascular diseases mortality and developing of a stroke were more frequent in the group accepting aliskiren than in the group accepting placebo, and messages about the undesirable phenomena and the serious undesirable phenomena (hyperpotassemia, hypotension and a renal failure) which are of interest were more frequent in the group accepting aliskiren than in the group accepting placebo.
Indications
- treatment of essential arterial hypertension easy and moderate severity
- treatment in the first 24 hours of patients with an acute myocardial infarction with signs or symptoms (or without those) heart failure which concerning a hemodynamics are stable and by which did not carry out thrombolytic therapy.
The route of administration and doses
of Zokardis® can be accepted to, in time or after a meal. The dose has to be picked up individually.
Arterial hypertension
Selection of a necessary dose should be carried out by measurement of arterial blood pressure just before acceptance of the following dose. The dose should be increased at an interval of four weeks.
Patients without water-salt deficit
Treatment it is necessary to begin with a dose 15 mg once a day and to raise a dose to achievement of optimum arterial blood pressure.
Usually effective dose makes 30 mg a day.
The maximum dose makes 60 mg a day, accepted in one or two receptions.
In case of inefficiency other hypotensive drugs, such, for example, as diuretics can be added.
Patients with suspicion on existence water solevoogo deficit
Arterial hypotension after reception of the first dose can be observed at patients from group of the increased risk (see. "Special instructions"). At the beginning of therapy it is necessary to eliminate with inhibitors of the angiotensin-converting enzyme (ACE) salt and/or water deficit, to stop therapy by diuretics within two-three days prior to intake of APF inhibitor, since the dose making 15 mg a day. If it is impossible, then it is necessary to begin with a dose 7.5 mg a day.
Patients with high risk of approach of heavy acute arterial hypotension should be observed attentively preferably in stationary conditions until the maximum effect after use of the first dose, and every time when increase a dose of APF inhibitor and/or diuretic is reached. All this also concerns patients with stenocardia or a cerebrovascular disease at which excessive arterial hypotension can lead to a myocardial infarction or to an acute disorder of cerebral circulation.
A dosage at patients with damage of kidneys or being on treatment by a hemodialysis
At the patients having arterial hypertension with pathology of kidneys of easy degree (clearance of creatinine & gt, 45 ml/min.) the same doses and the mode of reception Zokardisa® (once a day), as at patients with normal function of kidneys can be applied. At patients with average and heavy degree of a renal failure (the clearance of creatinine & lt, 45 ml/min.) Zokardis® should be applied in a half therapeutic dose, the dosage mode (once a day) does not demand change.
The initial dose and the dose Zokardisa® mode for the patients having arterial hypertension and being on dialysis makes the quarter of a dose appointed to patients with normal function of kidneys.
Recent clinical trials showed the high frequency of anafilaktoidnopodobny reactions at the patients accepting APF inhibitors during a hemodialysis using dialysis membranes with a high capacity or during an aferez of lipids of low density (see. "Special instructions").
The dosage
At elderly patients with normal clearance of creatinine is not required from elderly patients corrections of a dose.
At elderly patients with the lowered clearance of creatinine (less than 45 ml/min.) the reception of a half of a day dose is recommended.
The clearance of creatinine can be calculated, proceeding from serumal creatinine, on the following formula:
Clearance (140 – age) x the weight (kg)
of creatinine (ml/min.) = ____________________________
syvorot. creatinine (mg/dl) x 72
formula Given above allows to calculate clearance of creatinine at men. For women the received value should be increased by 0.85.
The dosage in abnormal liver functions
At the patients having arterial hypertension and an abnormal liver function easy or moderate severity, an initial dose of Zokardisa® makes a half of the dose applied at patients with normal function of a liver.
To patients with heavy degree of an abnormal liver function of Zokardis® it is contraindicated.
Children
Safety or efficiency of use of Zokardisa® for children was not established. Therefore at children it should not be applied.
The acute myocardial infarction
Treatment of Zokardisom® should be begun within 24 hours after emergence of the first symptoms of a myocardial infarction and to continue within six weeks.
It is necessary to apply the following scheme of a dosage:
1 and 2 days: To 7.5 mg there are each 12 hours
3 and 4 days: To 15 mg there are each 12 hours
the 5th day and further: To 30 mg there are each 12 hours
in case of low systolic arterial blood pressure (£120 mm Hg.) in an initiation of treatment or within the first three days after a myocardial infarction, the daily dose should not be increased. In case of arterial hypotension (£100 mm Hg.) treatment can be continued by a dose which was already earlier well transferred. In case of heavy arterial hypotension (systolic arterial blood pressure is less than 90 mm Hg., at two consecutive measurements with an interval not less than one hour) the reception of Zokardisa® should be stopped.
After 6 weeks of treatment the condition of patients has to be analyzed and treatment should be stopped at patients without symptoms of dysfunction of a left ventricle or heart failure. If these signs remained, treatment can be continued for a long time.
Patients should perform also the corresponding standard treatment, such as treatment by nitrates, aspirin or beta-blockers.
A dosage at elderly patients
of Zokardis® it is necessary to apply with care at patients 75 years with a myocardial infarction are more senior.
The dosage at patients with damage of kidneys or
the Efficiency and safety of use of Zokardisa® for patients which are on dialysis with a myocardial infarction and with a renal failure or exposed to dialysis was not established. Therefore at such patients of Zokardis® it is not necessary to apply.
The dosage at patients in abnormal liver functions
Efficiency and safety of use of Zokardisa® for patients with a myocardial infarction and with an abnormal liver function was not established. Therefore at such patients this drug should not be used.
Side effects
are listed below all side effects observed in clinical practice at the patients treated by Zokardisom®.
Often (≥1/100, but & lt, 1/10)
- dizziness, a headache
- cough
- nausea, vomiting
- increased fatigue
Infrequently (≥1/1000, but ≤1/100)
- rash
- myotonia
- an asthenia
Seldom (≥1/10000, but & lt, 1/1000)
a Quincke's disease
the Following side effects were observed in connection with intake of APF inhibitors:
Seldom (≥1/10000, but & lt, 1/1000)
- a depression, differences of mood, sleep disorder and confusion of consciousness
- blurring of sight
- a ring in ears
- hyperaemia of integuments
- short wind, sinusitis, rhinitis, a glossitis, bronchitis and a bronchospasm
- a hyperhidrosis
- erectile dysfunction
- disturbances of urination
It is very rare (≤1/10000)
- a hypoglycemia
- a Quincke's disease with localization in a small intestine
- peripheral hypostasis and thorax pain
Frequency is unknown (it is impossible to estimate on the available data)
- an agranulocytosis and a pancytopenia
- hemolytic anemia at patients with deficit glyukozo-6-fosfatdegidrogenazy
- paresthesia, a disgeziya, balance disturbance
- at an initial stage of therapy and at increase in a dose the heavy arterial hypotension was observed. This phenomenon is characteristic of certain risk groups (see. "Special instructions"). Along with arterial hypotension such symptoms as dizziness, feeling of weakness, a disorder of vision can be observed, occasionally - consciousness disturbance (syncope)
- concerning APF inhibitors in connection with arterial hypotension was reported about separate cases of appearance of tachycardia, heartbeat, arrhythmias, stenocardia, a myocardial infarction
- appearance of a Quincke's disease with involvement of the person and an oropharyngeal zone at a small number of patients contacted effect of APF inhibitors. In some cases the Quincke's disease with involvement of upper airways caused obstruction of airways with a lethal outcome
- abdominal pains, diarrhea, a constipation or dryness in a mouth
- the pancreatitis and intestinal impassability connected with APF inhibitors
- cholestatic jaundice and hepatitis
- allergic reactions and reactions of hypersensitivity, such as itching, small tortoiseshell, multiformny erythema, Stephens-Johnson's syndrome, epidermal toxic necrolysis, psoriazopodobny rashes, alopecia. These phenomena can be followed by fever, myalgia, an arthralgia, an eosinophilia and/or the raised caption of anti-nuclear antibodies (ANA)
- myalgia
- a renal failure or an acute renal failure
- increase in level of urea and creatinine in blood which after drug withdrawal return to normal, in particular in the presence of a renal failure, heavy heart failure and renovascular hypertensia
- the lowered level of hemoglobin and a hematocrit, reduction of quantity of thrombocytes and leukocytes
- increase in content of enzymes of a liver and bilirubin in serum.
Messages about possible undesirable reactions
the Message about possible side effects after registration of medicine plays an important role. It allows to continue observation of a ratio "advantage/risk" concerning this medicine. From workers of health care it is required to report about any possible side effects via the national warning system.
Contraindications
- hypersensitivity to a calcium zofenopril, to the APF any other inhibitor or to one of the excipients which are a part of drug
- the Quincke's disease in the anamnesis connected with the previous treatment by APF inhibitor
- a hereditary/idiopathic Quincke's disease
- heavy degree of an abnormal liver function
- the second and third trimester of pregnancy
- the women of childbearing age who are not applying effective contraception
- a bilateral renal artery stenosis or a unilateral renal artery stenosis in case of one kidney
- combined use of Zokardis and the drugs containing aliskiren is contraindicated to patients with diabetes or a renal failure (SKF & lt, 60 ml/min. / 1.73 to sq.m)
- children's and teenage age up to 18 years
- patients from rare hereditary neperenosimomtyyu galactoses, deficiency of lactose, glucose galactose metabolism disturbance.
Medicinal interactions
combined use
Double blockade system renin-angiotensin-aldosteronovoy is not recommended
Data of clinical trials show that the double blockade the system renin-angiotensin-aldosteronovoy (SRAA) connected with combined use of APF inhibitors and blockers of receptors of angiotensin II or an aliskiren leads to increase in frequency of the undesirable phenomena, such as hypotension, hyperpotassemia and depression of function of kidneys (including an acute renal failure), in comparison with use of one means operating on RAAS.
Kaliysberegayushchy diuretics or potassium additives. APF inhibitors reduce the potassium loss caused by diuretic. Kaliysberegayushchy diuretics, for example, can lead Spironolactonum, Triamterenum or amiloride, potassium additives or substitutes of salts containing potassium to significant increase in level of potassium in serum. If owing to the established hypopotassemia the combined use of these medicines is shown, they should be used with care and also with frequent control of serumal potassium and the ECG.
At combined use the observance of precautionary measures
Diuretics is required (thiazide or loopback).
The previous treatment by high doses of diuretics can lead to dehydration and emergence of risk of developing arterial hypotension at an initial stage of treatment zofenoprily. Hypotensive effects can be reduced by cancellation of diuretics, increase in consumption of liquid or salt or beginning treatment with low doses of a zofenopril.
Lithium. It was reported about reversible increase in concentration of serumal lithium and its toxicity at joint prescribing of lithium with APF inhibitors. Combined use of thiazide diuretics with drugs of lithium can increase risk of lithium intoxication. This danger increases against the background of intake of APF inhibitors which also increase risk of lithium intoxication.
Therefore Zokardis® is not recommended to appoint together with lithium, and in case of such need it is necessary to control carefully lithium level in serum.
Gold. It was reported that at the patients accepting APF inhibitors nitritoidny reactions develop more often (vazodilatation symptoms, including rush of blood, nausea, dizziness and hypotension which can have very difficult character).
The anesthetizing medicines. APF inhibitors can enhance hypotensive effect of the general anesthetics (for example, thiopental)
Drugs / tricyclic antidepressants / anti-psychotics / barbiturates
orthostatic arterial hypotension Can meet.
Other antihypertensives (e.g., beta-blockers, alpha blockers, antagonists of calcium). The additive hypotensive effect or potentiation of effect of drugs is possible. Nitroglycerine, other nitrates and vazodilatator should be applied with care.
Cimetidinum. Increase in risk of emergence of hypotensive effect is possible.
Cyclosporine. The increased risk of dysfunction of kidneys at combined use of APF inhibitors.
Allopyrinolum, procaineamide, cytostatics and immunodepressants. At combined use with APF inhibitors the risk of emergence of reactions of hypersensitivity increases. Data on other APF inhibitors (for example, captopril) indicate the increased risk of a leukopenia when sharing with drugs of this group.
Antidiabetic means. In rare instances APF inhibitors enhance hypoglycemic effects of insulin and oral antidiabetic means (e.g., sulphonylurea) at patients with diabetes. In such cases, at joint appointment with APF inhibitors, perhaps, it is necessary to reduce a dose of antidiabetic means.
A hemodialysis with use of dialysis membranes with a high capacity. At simultaneous use with APF inhibitors the risk of emergence of anaphylactoid reactions increases.
Cytostatics, immunodepressants, system corticosteroids and procaineamide. Combined use with APF inhibitors can result in the increased risk of emergence of a leukopenia.
It is necessary to consider at joint appointment
Non-steroidal anti-inflammatory drugs (including ASK in a dose ³ 3 g/day). Intake of non-steroidal anti-inflammatory drugs can reduce hypotensive effect of APF inhibitor. Besides, it was described that NPVS and APF inhibitors in addition increase the level of serumal potassium while function of kidneys can worsen. These effects are, in principle, reversible and meet especially at patients with impaired renal function. The acute renal failure, especially at patients with impaired renal function, for example, at the elderly or dehydrated patients is in rare instances observed.
Antacids. Reduce bioavailability of APF inhibitors.
Sympathomimetics. Can reduce hypotensive effect of APF inhibitors. It is necessary to watch carefully such patients to be convinced of achievement of desirable effect.
Food. Can reduce speed, but not extent of absorption of a zofenopril of calcium.
Additional information
Clinical data on direct interaction of a zofenopril with other medicines which are metabolized by cytochrome P enzymes, no. However researches of metabolism in vitro conducted with zofenoprily showed lack of potential interaction with medicine which is metabolized by cytochrome P enzymes.
Special instructions
Arterial hypotension
As well as other APF inhibitors, Zokardis® can cause a sharp lowering of arterial pressure, especially after the first dose though symptomatic arterial hypotension is seldom observed at patients with uncomplicated arterial hypertension.
Its emergence in patients with disturbance of water salt metabolism owing to therapy by diuretics, diets with salt restriction, owing to dialysis, diarrhea or vomiting is more probable and also at heavy renin - dependent arterial hypertension.
At patients with heavy heart failure and with the accompanying renal failure or without that symptomatic arterial hypotension was observed. This phenomenon is more probable at patients with higher degree of heart failure that is expressed in use of high doses of loopback diuretics, a hyponatremia or renal dysfunction. At patients with the increased risk of symptomatic arterial hypotension the treatment should be begun under careful medical observation, it is preferable in the conditions of a hospital, since low doses. It is necessary to approach selection of further doses with care.
At an initial stage of therapy of Zokardisom® the treatment by diuretics should be stopped, whenever possible, temporarily.
This approach is applicable also to patients with stenocardia or with cerebrovascular pathology at which excessive reduction of arterial blood pressure can lead to a myocardial infarction or an acute disorder of cerebral circulation.
If arterial hypotension develops, the patient it is necessary to put on a back. Intravenous administration of normal saline solution for completion of OCK can be required. Appearance of arterial hypotension after acceptance of the first dose does not exclude the consecutive titrated selection of a dose of medicine after performing effective treatment.
With heart failure and normal or low arterial blood pressure of Zokardis® can cause an additional lowering of arterial pressure in some patients. This effect is predictable and usually does not serve as the reason for treatment cancellation. If arterial hypotension becomes symptomatic, reduction of a dose or cancellation of Zokardisa® can be required.
Arterial hypotension in an acute myocardial infarction
At patients with an acute myocardial infarction, with risk of emergence of additional serious hemodynamic insufficiency owing to treatment by a vazodilatator, treatment of Zokardisom® cannot be begun. Those are patients with systolic arterial blood pressure & lt, 100 mm Hg. or with cardiogenic shock. Treatment of Zokardisom® of such patients with an acute myocardial infarction can lead to heavy arterial hypotension. In case of persistent arterial hypotension (systolic arterial blood pressure & lt, 90 mm Hg. within more than one hour) treatment of Zokardisom® should be interrupted. At patients with heavy heart failure after an acute myocardial infarction of Zokardis® patients should appoint only with a stable hemodynamics.
Patients with an acute myocardial infarction in combination with an abnormal liver function
the Efficiency and safety of use of Zokardisa® for patients with a myocardial infarction in combination with an abnormal liver function was not established. Therefore at such patients this drug should not be used.
Elderly patients
At patients are more senior than 75 years with a myocardial infarction of Zokardis® it is necessary to apply with care.
Patients with renovascular arterial hypertension
At treatment by APF inhibitors of patients with renovascular arterial hypertension and already available bilateral stenosis of renal arteries or a unilateral renal artery stenosis the patients with one kidney have an increased risk of developing of heavy hypotension and renal failure. At the same time treatment by diuretics can serve as the promoting factor. The renal failure can be followed only by little changes of level of serumal creatinine even at patients with a unilateral renal artery stenosis. If nevertheless it is considered necessary absolutely, then treatment of Zokardisom® should be begun in a hospital under fixed medical observation with low doses, carefully selecting the following doses. Treatment by diuretics should be stopped temporarily at the beginning of therapy of Zokardisom®, and within the first several weeks of therapy it is necessary to monitor function of kidneys carefully.
Patients with a renal failure
At patients with a renal failure of Zokardis® it is necessary to apply with care as they need the lowered dose. During therapy it is necessary to carry out the corresponding careful control of function of kidneys. It was reported about a renal failure when prescribing APF inhibitors, mainly, at patients with heavy heart failure or at the kidneys having diseases, including a renal artery stenosis. At some patients without the obvious already existing pathology of kidneys of a proa
to Develop
of medicine Зокардис® 7.5 Зокардис® 30
the Trade name
Зокардис® 7.5 Зокардис® 30
International unlicensed
name Zofenopril Lekarstvennaya
the Tablet form film coated 7.5 mg and 30 mg
Structure
One tablet contains
active agent: 7.5 mg and 30 mg of a zofenopril of calcium that there correspond
7.2 mg and 28.7 mg of a zofenopril
excipients: microcrystalline cellulose, lactoses monohydrate, starch corn, magnesium stearate, silicon dioxide colloidal anhydrous
structure of a cover:
a gipromelloza, the titan dioxide (E 171), a macrogoal 400, a macrogoal 6000
Description
of Зокардис® 7.5 mg
of the Tablet of round shape, with a biconvex surface, film coated white
Зокардис® 30 color of mg
of a tablet of oblong shape, film coated white color, with risky on both parties. The tablet can be divided into two identical parts.
Pharmacotherapeutic group
the Drugs influencing a system renin-angiotensin. Angiotenzinkonvertiruyushchy enzyme (AKF) inhibitors. Zofenopril.
The ATX C09AA15 code
the Pharmacological
Zofenopril Pharmacokinetics properties of calcium is pro-medicine as active inhibitor is free sulfhydryl connection — zofenoprilat — received by thioradio hydrolysis.
Absorption
Zofenopril of calcium is quickly and completely absorbed at oral administration and is exposed to almost full transformation in zofenoprilat which maximum concentration in blood is reached in 1.5 hours after reception of an oral dose of Zokardisa®. The kinetics of a single dose is linear in the range of doses of 10-80 mg of a zofenopril of calcium. After use of 15-60 mg of a zofenopril of calcium within 3 weeks the accumulation is not observed. Presence of food at digestive tract reduces speed, but not extent of absorption, but the areas under curve (AUC) of the zofenoprilat are almost identical being able on an empty stomach and after a meal.
Distribution
About 88% of the circulating radioactivity measured by ex-Vivo after reception of a dose of a zofenopril of calcium marked radioactive isotope, contacts protein of plasma, and the established volume of distribution is 96 liters.
Metabolism
In urine of the person after reception of a dose of a zofenopril of calcium, marked radioactive isotope identified eight metabolites making 76% of radioactivity of urine. The main metabolite is zofenoprilat (22%) which then is metabolized in several ways, including conjugation with glucuronic acid (17%), cyclization and conjugation with glucuronic acid (13%), conjugation with cysteine (9%) and S-methylation of thiol group (8%). After oral administration of a zofenopril of calcium the elimination half-life of the zofenoprilat makes 5.5 hours, and its general clearance - 1300 ml/min.
Removal
Marked radioactive isotope zofenoprilat, entered intravenously, is removed with urine (76%) and a stake (16%), and after peroral marked radioactive isotope of a dose of a zofenopril of calcium in urine and Calais 69% and 26% of radioactivity respectively are found that demonstrates existence of two ways of elimination - kidneys and a liver.
The pharmacokinetics
At normal renal function at elderly patients of dose adjustment is not required from elderly patients.
Pharmacokinetics in renal dysfunction
based on comparison of key pharmacokinetic parameters of the zofenoprilat which assessment was carried out after oral administration of a zofenopril of calcium marked radioactive isotope, it is revealed that at patients with a renal failure of easy degree (clearance of creatinine & gt, 45 and & lt, 90 ml/min.) zofenoprit it is brought out of an organism with the same speed, as at patients with normal renal function (clearance of creatinine & gt, 90 ml/min.).
At patients with a renal failure of average and heavy degree (7 - 44 ml/min.) the speed of elimination is reduced, approximately, to 50% of normal. It indicates that this group of patients should appoint a half of a usual initial dose of Zokardisa®.
Patients in an end-stage have diseases of the kidneys which are on a hemodialysis and peritoneal dialysis, the speed of elimination is reduced to 25% of normal. It indicates that this group of patients should appoint a quarter of a usual initial dose of Zokardisa®.
Pharmacokinetics in liver dysfunction
At patients with dysfunction of a liver easy or moderate severity which were given a single dose of a zofenopril of calcium marked radioactive isotope, values of Tmaks and Smaks for the zofenoprilat were similar to the values received at healthy patients. However PPK values (the areas under a curve, AUC) at patients with cirrhosis were approximately twice more in comparison with PPK values at normal patients, indicating that patients with dysfunction of a liver easy or moderate severity should appoint a half of an initial dose of Zokardisa® appointed to patients with normal function of a liver.
Data on pharmacokinetics of a zofenopril and the zofenoprilat at patients with dysfunction of a liver of heavy degree are absent therefore to these patients zofenoprit is contraindicated.
The pharmacodynamics
Favorable action of Zokardisa® in cases of arterial hypertension and acute myocardial infarction is result, mainly, of suppression plasmatic system renin-angiotensin-aldosteronovoy. Result of inhibition of APF (Ki of 0.4 nanometers in lungs of a rabbit for argininovy salt of the zofenoprilat) is decrease in level of angiotensin II in blood plasma which leads to decrease in vasoconstrictive activity and to hyposecretion of Aldosteronum. In spite of the fact that this decrease is rather small, along with loss of sodium and liquid perhaps some increase in potassium concentration in blood serum. On secretion of renin the increase in activity of plasma renin is result of the termination of negative feedback of angiotensin II.
The activity of plasma APF within 24 hours after single dose of a zofenopril of calcium in a dose of 30 mg and 60 mg is suppressed respectively for 53.4% and 74.4%.
As a result of inhibition of APF the activity of the circulating and local kallikrein-kinin system which promotes a peripheral vazodilatation by activation of a prostaglandinovy system increases. It is possible that the hypotensive effect of a zofenopril of calcium is connected with this mechanism which is perhaps, one of the causes of side effects.
At patients with arterial hypertension the use of Zokardisa® leads to a lowering of arterial pressure in a prone position and standing approximately to the same extent with lack of compensatory increase in heart rate. Average system vascular resistance after use of Zokardisa® tends to reduction.
From some patients the achievement of an optimum lowering of arterial pressure requires several weeks of therapy. The stable hypotensive effect is reached by long therapy.
Sudden interruption of therapy was not connected with sharp increase in arterial blood pressure. Now the actions of Zokardisa® given relatively on incidence and mortality of the patients having arterial hypertension no.
Though manifestation of hypotensive action was observed at persons of all studied races, nevertheless reaction of an organism at the patients of negroid race having arterial hypertension (usually it is populations in which the lowrenine form of arterial hypertension is observed) on monotherapy by APF inhibitor on average is less expressed than at patients of other races. At additional therapy by diuretics this difference is not observed.
The clinical effect reached as a result of timely use of Zokardisa® in a myocardial infarction can be connected with many factors, such as decrease in level of angiotensin II in plasma (i.e. suppression of process of remodeling of ventricles which can negatively influence the forecast in case of a heart attack) and increase in concentration of dilators in plasma and cells (prostaglandin - a kinin system).
Randomized placebo - controlled clinical trial of a zofenopril is carried out with participation of 1556 patients a myocardial infarction of a front wall who were not exposed to thrombolytic therapy. Treatment was begun within 24 hours and continued for 6 weeks. Frequency of primary combined final point (heavy heart failure and/or death within 6 weeks) was reduced at patients who were treated zofenoprily (zofenoprit 7.1%, placebo of 10.6%). Within one year the survival rate in group of the patients accepting Zokardis® was higher, than in group of not accepting Zokardis®.
Combined use of APF inhibitors and blockers of receptors of angiotensin II was investigated in two large-scale, randomized, controlled studies (ONTARGET (ONgoing Telmisartan Alone and in a combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)).
ONTARGET represented the research conducted at patients with a cardiovascular or cerebrovascular disease in the anamnesis or the diabetes 2 types which is followed by signs of damage of a target organ. VA NEPHRON-D represented the research conducted at patients with diabetes 2 types and a diabetic nephropathy. These researches did not reveal significant favorable impact on an outcome of renal and/or cardiovascular diseases and on mortality from them while in comparison with monotherapy the increased risk of development of a hyperpotassemia, acute damage of kidneys and/or hypotonias took place. Considering similarity of pharmakodinamichesky properties, these results are also applicable for other APF inhibitors and blockers of receptors of angiotensin II.
Combined use of APF inhibitors and blockers of receptors of angiotensin II contraindicated at patients with a diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) represented the research conducted for identification of positive effect from addition of an aliskiren to standard therapy by APF inhibitors or blockers of receptors of angiotensin II at patients with diabetes 2 types and a chronic disease of kidneys, a cardiovascular disease, or having both diseases. This research was interrupted in connection with the increased risk of undesirable outcomes earlier. Cardiovascular diseases mortality and developing of a stroke were more frequent in the group accepting aliskiren than in the group accepting placebo, and messages about the undesirable phenomena and the serious undesirable phenomena (hyperpotassemia, hypotension and a renal failure) which are of interest were more frequent in the group accepting aliskiren than in the group accepting placebo.
Indications
- treatment of essential arterial hypertension easy and moderate severity
- treatment in the first 24 hours of patients with an acute myocardial infarction with signs or symptoms (or without those) heart failure which concerning a hemodynamics are stable and by which did not carry out thrombolytic therapy.
The route of administration and doses
of Zokardis® can be accepted to, in time or after a meal. The dose has to be picked up individually.
Arterial hypertension
Selection of a necessary dose should be carried out by measurement of arterial blood pressure just before acceptance of the following dose. The dose should be increased at an interval of four weeks.
Patients without water-salt deficit
Treatment it is necessary to begin with a dose 15 mg once a day and to raise a dose to achievement of optimum arterial blood pressure.
Usually effective dose makes 30 mg a day.
The maximum dose makes 60 mg a day, accepted in one or two receptions.
In case of inefficiency other hypotensive drugs, such, for example, as diuretics can be added.
Patients with suspicion on existence water solevoogo deficit
Arterial hypotension after reception of the first dose can be observed at patients from group of the increased risk (see. "Special instructions"). At the beginning of therapy it is necessary to eliminate with inhibitors of the angiotensin-converting enzyme (ACE) salt and/or water deficit, to stop therapy by diuretics within two-three days prior to intake of APF inhibitor, since the dose making 15 mg a day. If it is impossible, then it is necessary to begin with a dose 7.5 mg a day.
Patients with high risk of approach of heavy acute arterial hypotension should be observed attentively preferably in stationary conditions until the maximum effect after use of the first dose, and every time when increase a dose of APF inhibitor and/or diuretic is reached. All this also concerns patients with stenocardia or a cerebrovascular disease at which excessive arterial hypotension can lead to a myocardial infarction or to an acute disorder of cerebral circulation.
A dosage at patients with damage of kidneys or being on treatment by a hemodialysis
At the patients having arterial hypertension with pathology of kidneys of easy degree (clearance of creatinine & gt, 45 ml/min.) the same doses and the mode of reception Zokardisa® (once a day), as at patients with normal function of kidneys can be applied. At patients with average and heavy degree of a renal failure (the clearance of creatinine & lt, 45 ml/min.) Zokardis® should be applied in a half therapeutic dose, the dosage mode (once a day) does not demand change.
The initial dose and the dose Zokardisa® mode for the patients having arterial hypertension and being on dialysis makes the quarter of a dose appointed to patients with normal function of kidneys.
Recent clinical trials showed the high frequency of anafilaktoidnopodobny reactions at the patients accepting APF inhibitors during a hemodialysis using dialysis membranes with a high capacity or during an aferez of lipids of low density (see. "Special instructions").
The dosage
At elderly patients with normal clearance of creatinine is not required from elderly patients corrections of a dose.
At elderly patients with the lowered clearance of creatinine (less than 45 ml/min.) the reception of a half of a day dose is recommended.
The clearance of creatinine can be calculated, proceeding from serumal creatinine, on the following formula:
Clearance (140 – age) x the weight (kg)
of creatinine (ml/min.) = ____________________________
syvorot. creatinine (mg/dl) x 72
formula Given above allows to calculate clearance of creatinine at men. For women the received value should be increased by 0.85.
The dosage in abnormal liver functions
At the patients having arterial hypertension and an abnormal liver function easy or moderate severity, an initial dose of Zokardisa® makes a half of the dose applied at patients with normal function of a liver.
To patients with heavy degree of an abnormal liver function of Zokardis® it is contraindicated.
Children
Safety or efficiency of use of Zokardisa® for children was not established. Therefore at children it should not be applied.
The acute myocardial infarction
Treatment of Zokardisom® should be begun within 24 hours after emergence of the first symptoms of a myocardial infarction and to continue within six weeks.
It is necessary to apply the following scheme of a dosage:
1 and 2 days: To 7.5 mg there are each 12 hours
3 and 4 days: To 15 mg there are each 12 hours
the 5th day and further: To 30 mg there are each 12 hours
in case of low systolic arterial blood pressure (£120 mm Hg.) in an initiation of treatment or within the first three days after a myocardial infarction, the daily dose should not be increased. In case of arterial hypotension (£100 mm Hg.) treatment can be continued by a dose which was already earlier well transferred. In case of heavy arterial hypotension (systolic arterial blood pressure is less than 90 mm Hg., at two consecutive measurements with an interval not less than one hour) the reception of Zokardisa® should be stopped.
After 6 weeks of treatment the condition of patients has to be analyzed and treatment should be stopped at patients without symptoms of dysfunction of a left ventricle or heart failure. If these signs remained, treatment can be continued for a long time.
Patients should perform also the corresponding standard treatment, such as treatment by nitrates, aspirin or beta-blockers.
A dosage at elderly patients
of Zokardis® it is necessary to apply with care at patients 75 years with a myocardial infarction are more senior.
The dosage at patients with damage of kidneys or
the Efficiency and safety of use of Zokardisa® for patients which are on dialysis with a myocardial infarction and with a renal failure or exposed to dialysis was not established. Therefore at such patients of Zokardis® it is not necessary to apply.
The dosage at patients in abnormal liver functions
Efficiency and safety of use of Zokardisa® for patients with a myocardial infarction and with an abnormal liver function was not established. Therefore at such patients this drug should not be used.
Side effects
are listed below all side effects observed in clinical practice at the patients treated by Zokardisom®.
Often (≥1/100, but & lt, 1/10)
- dizziness, a headache
- cough
- nausea, vomiting
- increased fatigue
Infrequently (≥1/1000, but ≤1/100)
- rash
- myotonia
- an asthenia
Seldom (≥1/10000, but & lt, 1/1000)
a Quincke's disease
the Following side effects were observed in connection with intake of APF inhibitors:
Seldom (≥1/10000, but & lt, 1/1000)
- a depression, differences of mood, sleep disorder and confusion of consciousness
- blurring of sight
- a ring in ears
- hyperaemia of integuments
- short wind, sinusitis, rhinitis, a glossitis, bronchitis and a bronchospasm
- a hyperhidrosis
- erectile dysfunction
- disturbances of urination
It is very rare (≤1/10000)
- a hypoglycemia
- a Quincke's disease with localization in a small intestine
- peripheral hypostasis and thorax pain
Frequency is unknown (it is impossible to estimate on the available data)
- an agranulocytosis and a pancytopenia
- hemolytic anemia at patients with deficit glyukozo-6-fosfatdegidrogenazy
- paresthesia, a disgeziya, balance disturbance
- at an initial stage of therapy and at increase in a dose the heavy arterial hypotension was observed. This phenomenon is characteristic of certain risk groups (see. "Special instructions"). Along with arterial hypotension such symptoms as dizziness, feeling of weakness, a disorder of vision can be observed, occasionally - consciousness disturbance (syncope)
- concerning APF inhibitors in connection with arterial hypotension was reported about separate cases of appearance of tachycardia, heartbeat, arrhythmias, stenocardia, a myocardial infarction
- appearance of a Quincke's disease with involvement of the person and an oropharyngeal zone at a small number of patients contacted effect of APF inhibitors. In some cases the Quincke's disease with involvement of upper airways caused obstruction of airways with a lethal outcome
- abdominal pains, diarrhea, a constipation or dryness in a mouth
- the pancreatitis and intestinal impassability connected with APF inhibitors
- cholestatic jaundice and hepatitis
- allergic reactions and reactions of hypersensitivity, such as itching, small tortoiseshell, multiformny erythema, Stephens-Johnson's syndrome, epidermal toxic necrolysis, psoriazopodobny rashes, alopecia. These phenomena can be followed by fever, myalgia, an arthralgia, an eosinophilia and/or the raised caption of anti-nuclear antibodies (ANA)
- myalgia
- a renal failure or an acute renal failure
- increase in level of urea and creatinine in blood which after drug withdrawal return to normal, in particular in the presence of a renal failure, heavy heart failure and renovascular hypertensia
- the lowered level of hemoglobin and a hematocrit, reduction of quantity of thrombocytes and leukocytes
- increase in content of enzymes of a liver and bilirubin in serum.
Messages about possible undesirable reactions
the Message about possible side effects after registration of medicine plays an important role. It allows to continue observation of a ratio "advantage/risk" concerning this medicine. From workers of health care it is required to report about any possible side effects via the national warning system.
Contraindications
- hypersensitivity to a calcium zofenopril, to the APF any other inhibitor or to one of the excipients which are a part of drug
- the Quincke's disease in the anamnesis connected with the previous treatment by APF inhibitor
- a hereditary/idiopathic Quincke's disease
- heavy degree of an abnormal liver function
- the second and third trimester of pregnancy
- the women of childbearing age who are not applying effective contraception
- a bilateral renal artery stenosis or a unilateral renal artery stenosis in case of one kidney
- combined use of Zokardis and the drugs containing aliskiren is contraindicated to patients with diabetes or a renal failure (SKF & lt, 60 ml/min. / 1.73 to sq.m)
- children's and teenage age up to 18 years
- patients from rare hereditary neperenosimomtyyu galactoses, deficiency of lactose, glucose galactose metabolism disturbance.
Medicinal interactions
combined use
Double blockade system renin-angiotensin-aldosteronovoy is not recommended
Data of clinical trials show that the double blockade the system renin-angiotensin-aldosteronovoy (SRAA) connected with combined use of APF inhibitors and blockers of receptors of angiotensin II or an aliskiren leads to increase in frequency of the undesirable phenomena, such as hypotension, hyperpotassemia and depression of function of kidneys (including an acute renal failure), in comparison with use of one means operating on RAAS.
Kaliysberegayushchy diuretics or potassium additives. APF inhibitors reduce the potassium loss caused by diuretic. Kaliysberegayushchy diuretics, for example, can lead Spironolactonum, Triamterenum or amiloride, potassium additives or substitutes of salts containing potassium to significant increase in level of potassium in serum. If owing to the established hypopotassemia the combined use of these medicines is shown, they should be used with care and also with frequent control of serumal potassium and the ECG.
At combined use the observance of precautionary measures
Diuretics is required (thiazide or loopback).
The previous treatment by high doses of diuretics can lead to dehydration and emergence of risk of developing arterial hypotension at an initial stage of treatment zofenoprily. Hypotensive effects can be reduced by cancellation of diuretics, increase in consumption of liquid or salt or beginning treatment with low doses of a zofenopril.
Lithium. It was reported about reversible increase in concentration of serumal lithium and its toxicity at joint prescribing of lithium with APF inhibitors. Combined use of thiazide diuretics with drugs of lithium can increase risk of lithium intoxication. This danger increases against the background of intake of APF inhibitors which also increase risk of lithium intoxication.
Therefore Zokardis® is not recommended to appoint together with lithium, and in case of such need it is necessary to control carefully lithium level in serum.
Gold. It was reported that at the patients accepting APF inhibitors nitritoidny reactions develop more often (vazodilatation symptoms, including rush of blood, nausea, dizziness and hypotension which can have very difficult character).
The anesthetizing medicines. APF inhibitors can enhance hypotensive effect of the general anesthetics (for example, thiopental)
Drugs / tricyclic antidepressants / anti-psychotics / barbiturates
orthostatic arterial hypotension Can meet.
Other antihypertensives (e.g., beta-blockers, alpha blockers, antagonists of calcium). The additive hypotensive effect or potentiation of effect of drugs is possible. Nitroglycerine, other nitrates and vazodilatator should be applied with care.
Cimetidinum. Increase in risk of emergence of hypotensive effect is possible.
Cyclosporine. The increased risk of dysfunction of kidneys at combined use of APF inhibitors.
Allopyrinolum, procaineamide, cytostatics and immunodepressants. At combined use with APF inhibitors the risk of emergence of reactions of hypersensitivity increases. Data on other APF inhibitors (for example, captopril) indicate the increased risk of a leukopenia when sharing with drugs of this group.
Antidiabetic means. In rare instances APF inhibitors enhance hypoglycemic effects of insulin and oral antidiabetic means (e.g., sulphonylurea) at patients with diabetes. In such cases, at joint appointment with APF inhibitors, perhaps, it is necessary to reduce a dose of antidiabetic means.
A hemodialysis with use of dialysis membranes with a high capacity. At simultaneous use with APF inhibitors the risk of emergence of anaphylactoid reactions increases.
Cytostatics, immunodepressants, system corticosteroids and procaineamide. Combined use with APF inhibitors can result in the increased risk of emergence of a leukopenia.
It is necessary to consider at joint appointment
Non-steroidal anti-inflammatory drugs (including ASK in a dose ³ 3 g/day). Intake of non-steroidal anti-inflammatory drugs can reduce hypotensive effect of APF inhibitor. Besides, it was described that NPVS and APF inhibitors in addition increase the level of serumal potassium while function of kidneys can worsen. These effects are, in principle, reversible and meet especially at patients with impaired renal function. The acute renal failure, especially at patients with impaired renal function, for example, at the elderly or dehydrated patients is in rare instances observed.
Antacids. Reduce bioavailability of APF inhibitors.
Sympathomimetics. Can reduce hypotensive effect of APF inhibitors. It is necessary to watch carefully such patients to be convinced of achievement of desirable effect.
Food. Can reduce speed, but not extent of absorption of a zofenopril of calcium.
Additional information
Clinical data on direct interaction of a zofenopril with other medicines which are metabolized by cytochrome P enzymes, no. However researches of metabolism in vitro conducted with zofenoprily showed lack of potential interaction with medicine which is metabolized by cytochrome P enzymes.
Special instructions
Arterial hypotension
As well as other APF inhibitors, Zokardis® can cause a sharp lowering of arterial pressure, especially after the first dose though symptomatic arterial hypotension is seldom observed at patients with uncomplicated arterial hypertension.
Its emergence in patients with disturbance of water salt metabolism owing to therapy by diuretics, diets with salt restriction, owing to dialysis, diarrhea or vomiting is more probable and also at heavy renin - dependent arterial hypertension.
At patients with heavy heart failure and with the accompanying renal failure or without that symptomatic arterial hypotension was observed. This phenomenon is more probable at patients with higher degree of heart failure that is expressed in use of high doses of loopback diuretics, a hyponatremia or renal dysfunction. At patients with the increased risk of symptomatic arterial hypotension the treatment should be begun under careful medical observation, it is preferable in the conditions of a hospital, since low doses. It is necessary to approach selection of further doses with care.
At an initial stage of therapy of Zokardisom® the treatment by diuretics should be stopped, whenever possible, temporarily.
This approach is applicable also to patients with stenocardia or with cerebrovascular pathology at which excessive reduction of arterial blood pressure can lead to a myocardial infarction or an acute disorder of cerebral circulation.
If arterial hypotension develops, the patient it is necessary to put on a back. Intravenous administration of normal saline solution for completion of OCK can be required. Appearance of arterial hypotension after acceptance of the first dose does not exclude the consecutive titrated selection of a dose of medicine after performing effective treatment.
With heart failure and normal or low arterial blood pressure of Zokardis® can cause an additional lowering of arterial pressure in some patients. This effect is predictable and usually does not serve as the reason for treatment cancellation. If arterial hypotension becomes symptomatic, reduction of a dose or cancellation of Zokardisa® can be required.
Arterial hypotension in an acute myocardial infarction
At patients with an acute myocardial infarction, with risk of emergence of additional serious hemodynamic insufficiency owing to treatment by a vazodilatator, treatment of Zokardisom® cannot be begun. Those are patients with systolic arterial blood pressure & lt, 100 mm Hg. or with cardiogenic shock. Treatment of Zokardisom® of such patients with an acute myocardial infarction can lead to heavy arterial hypotension. In case of persistent arterial hypotension (systolic arterial blood pressure & lt, 90 mm Hg. within more than one hour) treatment of Zokardisom® should be interrupted. At patients with heavy heart failure after an acute myocardial infarction of Zokardis® patients should appoint only with a stable hemodynamics.
Patients with an acute myocardial infarction in combination with an abnormal liver function
the Efficiency and safety of use of Zokardisa® for patients with a myocardial infarction in combination with an abnormal liver function was not established. Therefore at such patients this drug should not be used.
Elderly patients
At patients are more senior than 75 years with a myocardial infarction of Zokardis® it is necessary to apply with care.
Patients with renovascular arterial hypertension
At treatment by APF inhibitors of patients with renovascular arterial hypertension and already available bilateral stenosis of renal arteries or a unilateral renal artery stenosis the patients with one kidney have an increased risk of developing of heavy hypotension and renal failure. At the same time treatment by diuretics can serve as the promoting factor. The renal failure can be followed only by little changes of level of serumal creatinine even at patients with a unilateral renal artery stenosis. If nevertheless it is considered necessary absolutely, then treatment of Zokardisom® should be begun in a hospital under fixed medical observation with low doses, carefully selecting the following doses. Treatment by diuretics should be stopped temporarily at the beginning of therapy of Zokardisom®, and within the first several weeks of therapy it is necessary to monitor function of kidneys carefully.
Patients with a renal failure
At patients with a renal failure of Zokardis® it is necessary to apply with care as they need the lowered dose. During therapy it is necessary to carry out the corresponding careful control of function of kidneys. It was reported about a renal failure when prescribing APF inhibitors, mainly, at patients with heavy heart failure or at the kidneys having diseases, including a renal artery stenosis. At some patients without the obvious already existing pathology of kidneys of a proa
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