Equator

General characteristics. Structure:

Active ingredients: 5 mg of an amlodipin (in the form of an amlodipin of a bezilat of 6,94 mg) and 10 mg of lisinopril (in the form of lisinopril of a dihydrate of 10,88 mg).

Excipients: magnesium stearate, carboxymethylstarch of sodium (type A), cellulose microcrystallic.

Pharmacological properties:

Pharmacodynamics. The combined drug containing active ingredients: lisinopril and амлодипин.

Lisinopril belongs to inhibitors of the angiotensin-converting enzyme (ACE), reduces levels of angiotensin II and Aldosteronum in blood, at the same time increasing the level of bradikinin - a vasodilating mediator. The system renin-angiotenzinovye influences on fabric. Reduces the general peripheric vascular resistance and the arterial pressure (AP), before - and an afterload, pressure in pulmonary capillaries, does not influence the frequency of a cordial rhythm, at the same time increase in minute volume of heart and strengthening of a blood-groove in kidneys is possible. Expands arteries more than veins. Improves blood supply of an ischemic myocardium. At prolonged use the hypertrophy of a myocardium and walls of arteries of resistant type decreases. Increases tolerance of a myocardium to exercise stresses at patients with chronic heart failure. Plays a part in recovery of function of the endothelium damaged as a result of a hyperglycemia. Increases life expectancy at chronic heart failure. Slows down progressing of dysfunction of a left ventricle after the myocardial infarction which is not complicated by heart failure. The hypotensive effect is observed in 1 hour after administration of drug inside, reaching a maximum in the 6th hour. Duration of action depends on a dose and makes the 24th hour. At prolonged treatment efficiency does not decrease. At the sharp termination of treatment of a syndrome of "cancellation" with sharp increase in the ABP does not arise. Despite primary effect which is shown in impact on renin-angiotensin-aldosteronovuyu system it is effective also at arterial hypertension with the low level of a renin. Lisinopril reduces an albuminuria not only thanks to decrease in the ABP, but also as a result of change of a hemodynamics of the glomerular device and its fabric structure. Does not influence sugar level in blood at patients with a diabetes mellitus and does not increase the frequency of cases of a hypoglycemia.

Amlodipin - a blocker of "slow" calcium channels of the III generation, has anti-anginal and hypotensive effect. Interferes with intake of calcium in cells of a myocardium and, more, in smooth muscle cells of a vascular wall. Reduces a tone of unstriated muscles of arterioles, peripheric vascular resistance and, therefore, Ad.Okazyvayet anti-anginal action due to expansion of arterioles and arteries and decrease in an afterload. Reduces oxygen requirement and power consumption of a myocardium since does not cause reflex tachycardia. Possibly, due to expansion of coronary arteries and arterioles increases supply with oxygen unimpaired (especially at vasospastic stenocardia) and ischemic sites of a myocardium. At stenocardia improves portability of an exercise stress, interferes with development of an attack of stenocardia and formation of an ischemic interval of ST, reducing the frequency of attacks of stenocardia and need for nitroglycerine use. Does not influence conductivity and contractility of a myocardium. Has long, dozozavisimy hypotensive effect. Does not reduce fraction of emission of a left ventricle. Reduces a hypertrophy of a left ventricle. Has anti-sclerous and cardioprotective effect at coronary heart disease. Its use against the background of therapy by digoxin, diuretics and APF inhibitors does not increase risk of death at patients with chronic heart failure (the III-IV Art. on NYHA classification). Slow absorption, wide distribution in an organism and slow removal provides the long action allowing to accept drug of 1 times a day. More, than on 24 h provides decrease in the ABP, considerable from the clinical point of view, in a sitting position and lying. Action develops gradually, in 2-4 h after reception and is not followed by arterial hypotension. Slows down aggregation of thrombocytes, strengthens glomerular filtering, has a weak natriuretic effect, at a diabetic nephropathy does not strengthen a microalbuminuria. Does not make negative impact on metabolic processes, does not change the level of plasma lipids. It can be appointed the patient with the accompanying bronchial asthma, a diabetes mellitus and gout. The lisinopril combination with amlodipiny in one medicine allows to prevent development of the possible undesirable effects caused by antiregulation any of active ingredients. So, a blocker of "slow" calcium channels, directly expanding arterioles, can lead to a delay of sodium and liquid in an organism, and, therefore, renin-angiotensin-aldosteronovuyu can activate system. APF inhibitor blocks this process, normalizes reactions to loading salts.

Pharmacokinetics. Lisinopril, being an active form of APF inhibitor, in not changed look gets to system blood circulation and in 6 h after intake reaches the maximum concentration in blood (90 ng/ml). Absorption of 30% (6-60%), bioavailability of 29%. Takes up only with APF, the elimination half-life of 12,6 h is not metabolized, removed with urine in not changed look. After removal of the most part of free lisinopril the fraction connected with APF is removed, providing long therapeutic effect. Gets through hematoencephalic and placental barriers. The patient with a renal failure appoint in smaller doses because of the broken secretory function of kidneys; it is dialyzed. After intake амлодипин slowly and almost completely (90%) it is soaked up from digestive tract and in 6-10 h reaches the maximum concentration. Reaches a saturation stage in a blood plasma for 7-8 days of regular reception. Bioavailability of 64-80%. The volume of distribution is about 20 l/kg. Communication with proteins of a blood plasma - 95-98%. Gets through a blood-brain barrier. Has effect of "primary passing", it is intensively metabolized in a liver (90%). The most part turns in a liver into an inactive metabolite. 10% of an amlodipin are allocated with urine in not changed look, 60% - in the form of metabolites, 20-25% - in the form of metabolites with bile through intestines; gets into breast milk. General clearance of 500 ml/min. Removal consists of two phases, an elimination half-life of a final phase 35-50 hour; it is not dialyzed. The elimination half-life at arterial hypertension - 48 h, at elderly patients, at a liver failure to 60 h, T1/2 increases to 65 h also at heavy heart failure, without reflecting degree of a renal failure. Approximately in one and too time the maximum concentration at young people and at elderly patients are reached. At elderly patients, the clearance of an amlodipin is slightly lower, the elimination half-life and the area under curve (AUC) are higher. Portability is identical therefore correction of a dose for elderly patients is not required. Interaction between deystvuyuishchm the substances which are a part of the drug Equator is improbable. AUC, time of achievement and size of the maximum concentration, elimination half-lives do not undergo changes in comparison with indicators of each separately taken active ingredient. Meal does not influence absorbability of active agents. Long circulation in an organism of both active ingredients does possible administration of drug of 1 times a day.

Indications to use:

Essential hypertensia (the patient to whom the combination therapy is shown).

Route of administration and doses:

Use of the Equator is offered if arterial pressure can be held in balance a combination of the drugs containing separately identical with the combined drug of a dose of lisinopril and an amlodipin.
Drug dose – for patients who do not accept other anti-hypertensive drugs – one tablet a day. Because food does not influence absorption of active ingredients, drug can be accepted irrespective of meal.
- It is offered to patients who accepted previously diuretics in two-three days prior to the beginning of a course of therapy by the Equator to interrupt a rate of diuretic. If it is impossible, an initial dose of drug 1/2 of a tablet in days. In this case, after reception of the first dose of drug, it is reasonable to keep the patient under medical observation because symptomatic hypotonia can develop. (See the Special Instructions point.)
- At a renal failure it is necessary to lower an initial dose of drug because release of lisinopril happens through kidneys. The maintenance dose needs to be defined individually, depending on reaction to drug and at rather often carried out control of functional indicators of kidneys and level of potassium and sodium in blood serum.
- At a liver failure allocation of an amlodipin from an organism can be late. The exact instruction of a dose is not available, but such patients can accept drug with extra care.

Features of use:

Considerable symptomatic hypotonia at patients who have a hyponatremia and/or a hypovolemia, in connection with reception of diuretics or from loss of a large amount of liquid for other reason (intensive sweating, long vomiting, diarrhea) can be observed. At emergence of hypotonia the patient needs to accept a prone position, in case of need to enter intravenously normal saline solution of sodium of chloride.
Prior to the beginning of a therapy course, it is necessary to eliminate a hyponatremia or a hypovolemia and at reception of the first doses of drug it is necessary to monitor effect of drug on arterial pressure.
In case of a stenosis of an aorta or a hypertrophic cardiomyopathy as all drugs expanding vessels, and the Equator it is necessary to apply with care, because of existence of a subaortic stenosis.

Renal failure:
At a renal artery stenosis (especially if narrowing from two parties is observed, or there is only one kidney and narrowing of the mouth of a renal artery is noted) if there is a hyponatremia and/or a hypovolemia, and also in case of a circulatory unefficiency, lisinopril can lead to deterioration in function of kidneys, to an acute renal failure which after therapy interruption, is usually reversible.
At reception of any drug from group of inhibitors of an angiotensin-converting enzyme, and at reception of lisinopril the Quincke's disease, with swelling of the person, extremities, lips, an epiglottis and a throat can appear. In that case it is necessary to stop immediately administration of drug and to leave the patient under observation of the doctor before total disappearance of signs.
If hypostasis meets on a face, lips and extremities, it usually spontaneously passes, but for decrease in intensity of signs it is possible to use antihistaminic drugs.
The Quincke's disease with hypostasis of a throat can lead to a fatal outcome. The paraglossa, an epiglottis or a throat can lead to obstruction of respiratory tracts therefore it is necessary to take immediately following therapeutic measures: to enter subcutaneously 0,1% adrenaline solution in a dose on 0,3-0,5 ml (0,3-0,5 mg) or 0,1 ml (0,1 mg) slowly, intravenously, then it is necessary to enter a glucocorticoid and antihistaminic drug under control of the vital functions of the patient.

Surgical intervention, anesthesia: at big operations or at use of drugs which cause hypotonia lisinopril slows down compensatory release of angiotensin-II. Hypotonia which is noted in this case according to the described mechanism, it is possible to eliminate with introduction of normal saline solution of table salt.
Carrying out a hemodialysis a membrane from polyacryle nitrile (for example, AN 69) to the patient receiving inhibitor of an angiotensin-converting enzyme can lead to an acute anaphylaxis therefore it is necessary to avoid their simultaneous use. It is necessary to use the filter of other type or to appoint anti-hypertensive drug of other group of action.

In certain cases, when the patient accepted inhibitor of an angiotensin-converting enzyme and desensitization to hymenopterous insects was carried out, anaphylactic reaction was noted. This life-threatening reaction can be avoided temporary interruption of a course of therapy by angiotensin-converting enzyme inhibitor.
Because unambiguously it is impossible to exclude a possibility of an agranulocytosis, periodically it is necessary to control a blood pattern.
At use of a standard dose of both active ingredients at advanced age higher level of these ingredients in a blood plasma therefore this patients should establish a drug dose with care though in efficiency of a considerable difference it was not noted at young and elderly patients was noted.
At damage of a liver time of semi-removal of an amlodipin increases. Because there are no exact data, drug can be used with care, with individual assessment of advantage and risk of therapy.

Pregnancy, feeding by a breast
Both reception of all inhibitors of an angiotensin-converting enzyme, and use of the Equator it is contraindicated during pregnancy; at pregnancy detection as it is possible earlier it is necessary to interrupt a therapy course.
Drugs of group of inhibitors of an angiotensin-converting enzyme, as well as lisinopril in the second and third trimester of pregnancy can lead to defeat or death of a fruit.
Use of the Equator during feeding by a breast is not shown because lisinopril is emitted in maternal milk. The possibility of penetration of an amlodipin into maternal milk is not known.
Influence on ability to driving of motor transport and to control of mechanisms
Drug can influence ability to driving of the car and control of mechanisms (especially at first reception) therefore it is necessary to define individually at what dose of drug it is possible to drive the car or to work in the conditions of the increased traumatism.

Side effects:

Side effects usually passing are also a little expressed therefore it is necessary to interrupt a therapy course seldom.
Very often: headache (8%), cough (5%) and dizziness (3%).
Often: weakness, diarrhea, nausea, vomiting, orthostatic lowering of arterial pressure, itch, skin rashes, hypostases, erubescence of the person, thorax pain, arthralgia (1-3%).
Emergence of other side effects meets at less, than 1% - and patients.
Owing to supersensitivity, the Quincke's disease, with swelling of the person, extremities, lips, an epiglottis and a throat can be created (at 0,1% - and patients). In that case it is necessary to interrupt immediately administration of drug, and the patient it is necessary to keep under control the doctor before total disappearance of signs. (See the Special Instructions point.)
Deviations in laboratory parameters
At use of other drugs from group of inhibitors of an angiotensin-converting enzyme, the agranulocytosis was found. Therefore at use of the Equator emergence of an agranulocytosis is possible.
Levels of hemoglobin and hematocrit at prolonged use of drug can slightly decrease.
The hyperpotassemia, increase in level of creatinine, residual nitrogen, and also increase in activity of liver enzymes and level of bilirubin in blood serum can meet, especially, at previously present disease of kidneys, a diabetes mellitus or a renovascular hypertension.

Another, seldom found undesirable effects.
- the feeling of heartbeat, tachycardia, is probable from excessive hypotonia, among patients with high risk of a myocardial infarction and stroke of a brain
- change of work of intestines, dryness in a mouth, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis, hyperplasia of gums
- hypostases, urtikariya, sweating, skin itch, alopecia.
- a renal failure, frequent desires on an urination, an oliguria, an anury, an acute renal failure, uraemia, a proteinuria, impotence.
 States with patologichny emergence of ANA (an antibody against nucleic acids), with increase in SOE (blood sedimentation rate) and with joint pains were published; and also emergence of a multiformny (exudative) erythema.

Interaction with other medicines:

To apply with extra care:
- with kaliysberegayushchy diuretics (e.g. Spironolactonum, amiloride, Triamterenum), with potassium and the edible salt containing potassium. In this case the hyperpotassemia can be created, especially at reduced function of kidneys therefore drug can be accepted under observation of the attending physician, at regular control of level of potassium in blood serum and functional indicators of kidneys.
To apply with care:
- with diuretics: the sharp lowering of arterial pressure can be noted (see. Special instructions).
- with other anti-hypertensive means (the additive action).
- with non-steroidal anti-inflammatory drugs (anti-hypertensive action can decrease).
- with lithium salts (extent of release of lithium therefore lithium level in a blood plasma should be controlled regularly can decrease).
- Lisinopril reduces potassium - the allocating effect of diuretics.

Contraindications:

Hypersensitivity to any of components of drug or to other derivatives of dihydropyridine; the Quincke's disease in the anamnesis including caused by use of other APF inhibitors, hereditary or idiopathic; hemodynamically significant stenosis of an aorta or mitral valve or hypertrophic cardiomyopathy; the expressed arterial hypotension; cardiogenic shock; pregnancy; lactation period; age up to 18 years (due to the lack of data on efficiency and safety of drug in this age group).

About Ostorozhnostyyu.Tserebrovaskulyarny diseases (including insufficiency of cerebral circulation), coronary heart disease, coronary insufficiency, the expressed bradycardia, tachycardia, chronic heart failure in a decompensation stage, easy or moderate degree of arterial hypotension, an acute myocardial infarction and within one month after it, a serious autoimmune illness (including a scleroderma, a system lupus erythematosus), oppression of a marrowy hemopoiesis, a diabetes mellitus, a hyperpotassemia, a state after transplantation of kidneys, a renal failure, a diet with sodium restriction, advanced age, a renal and/or liver failure.

USE AT PREGNANCY And during FEEDING GRUDYYU.PRIYOM of drug during pregnancy is contraindicated, at pregnancy identification treatment should be stopped as soon as possible. Reception of lisinopril in the second and third trimesters of pregnancy can do harm to a fruit and lead to his death as a result of impact on his kidneys (hypotonia, a renal failure, a hyperpotassemia). Reduction of amount of amniotic waters can lead to deformation of a skull and person, disturbance of development of extremities, a hypoplasia of lungs and death of a fruit. Data on similar and other influences in earlier durations of gestation are absent.

Administration of drug during feeding by a breast is contraindicated because of penetration of an amlodipin into breast milk. The data indicating penetration of lisinopril into breast milk no.

Overdose:

At overdose it is possible to expect the expressed expansion of peripheral vessels to which the excessive lowering of arterial pressure and reflex tachycardia accompanies. In such cases it is necessary to carry out a symptomatic treatment, it is necessary to lay the patient, to control cardiac performance, arterial pressure and it is necessary to control indicators of exchange of electrolytes and exchange of water, and also to carry out correction of these indicators, in case of need. At heavy hypotonia it is necessary to raise extremities and to add intravenously solutions for infusion, but at insufficiency of this therapy it is necessary to give vasoconstrictors (vazopressor) of peripheral action if their use is not contraindicated. For interruption of blocking of tubules of calcium it is possible to enter intravenously a calcium gluconate.
Because absorption of an amlodipin is dragged out on time, the gastric lavage can be effective.
Lisinopril can be deleted from an organism with a hemodialysis, but амлодипин because of the big connecting ability to proteins is not exposed to a hemodialysis (for the choice of a membrane for dialysis see point 4.4. Special instructions).

Storage conditions:

To store in original packaging at a temperature below 25 °C. To store in the place unavailable to children.

Issue conditions:

According to the recipe

Packaging:

10 tablets in the blister. One, two or three blisters in a cardboard box with the enclosed application instruction.