Equator - instructions for use, doses, side effects, contraindications

Active substances: 5 mg of amlodipine (in the form of amlodipine besylate 6.94 mg) and 10 mg of lisinopril (in the form of lisinopril dihydrate 10.88 mg).

Excipients: magnesium stearate 1.00 mg, sodium carboxymethyl starch (type A) 4.00 mg, microcrystalline cellulose (type 101) 90.54 mg, microcrystalline cellulose (type 12) 86.64 mg.

Description:

White or almost white round flat tablets with a bevel, with a risk on one side and with engraving "A+L" - another.

Pharmacotherapeutic group:antihypertensive agent combined (angiotensin-converting enzyme inhibitor and blocker of "slow" calcium channels).

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Combined drug containing active ingredients: lisinopril and amlodipine. Lisinopril - inhibitor of angiotensin-converting enzyme (ACE), reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases synthesis prostaglandins. Reduces the total. peripheral vascular resistance (OPSS), arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume crand increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin-aldosterone system (RAAS).

With long-term use, myocardial hypertrophy and the walls of arteries of resistive type decrease. Improves the blood supply of the ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with chronic cardiac insufficiency, slow the progression of left ventricular dysfunction in patients,who underwent myocardial infarction without clinical manifestations of heart failure. The onset of action is 1 hour after ingestion. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable effect develops after 1-2 months. With a sharp withdrawal of the drug, there was no pronounced increase in blood pressure. Despite the primary effect, which manifests itself in the effect on RAAS, it is also effective in hypertension with low renin activity. In addition to reducing blood pressure lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood the patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia. Amlodipine - a derivative of dihydropyridine, a blocker of "slow" calcium channels (BCCI), has an antianginal and antihypertensive effect. Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes).

Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles: with stenocardia reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reducesthe need for myocardium in oxygen. Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the flow of oxygen into the myocardium (especially with vasospastic angina); prevents spasm of the coronary arteries (including caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, slows the development of angina pectoris and the "ischemic" depression of the segment ST, reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

Has a long-term dose-dependent antihypertensive effect. Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant decrease in blood pressure over a period of 24 hours (in the patient's position "lying" and "standing"). Orthostatic hypotension in the appointment of amlodipine is rare.Does not cause a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductivity of the myocardium, does not cause a reflex increase in the heart rate (HR), inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have any adverse effects on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

Amlodipine + lisinopril

The combination of lisinopril with amlodipine in a single medicine can prevent the development of possible undesirable effects caused by one of the active substances. So, BCCC, directly expanding the arterioles, can lead to a delay in sodium and fluid in the body, and therefore can activate RAAS. The ACE inhibitor blocks this process.

Pharmacokinetics:

Lisinopril

Suction

After oral administration lisinopril absorbed from the gastrointestinal tract (GIT), its absorption can vary from 6 to 60%. Bioavailability is 29%. Eating does not affect the absorption of lisinopril.

Distribution

Almost does not bind to blood plasma proteins. The maximum concentration (Cmah) in the plasma of 90 ng / ml is reached after 6-7 hours. Permeability through the blood-brain and placental barrier is low.

Metabolism

Lizinopril is not biotransformed in the body.

Excretion

It is excreted by the kidneys unchanged. Half-life (T1 / 2) is 12.6 hours.

Pharmacokinetics in selected patient groups

In elderly patients, the concentration of lisinopril in the blood plasma and the area under the concentration-time curve (AUC) in 2 times more, than at patients of young age.

In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced.

In patients with renal insufficiency, the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, with an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.

Lizinopril is excreted from the body by hemodialysis.

Amlodipine

Suction

After oral administration amlodipine slowly and almost completely (90%) is absorbed from the digestive tract. The bioavailability of amlodipine is 64% -80%. Food intake does not affect the absorption of amlodipine.

Distribution

Most of the drug in the blood (95% -98%) binds to blood plasma proteins. FROMmah in serum is observed after 6-10 hours. Equilibrium concentrations (Css) are achieved after 7-8 days of therapy. The average volume of distribution is 20 l / kg body weight, indicating that most of the drug is in the tissues, and the smaller is in the blood.

Metabolism

Amlodipine undergoes a slow but active metabolism in the liver in the absence of a significant "primary transmission" effect. Metabolites do not have significant pharmacological activity.

Excretion

The derivation consists of two phases, T1/2 The final phase is 30-50 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites, 10% - in unchanged form, and 20-25% - in the form of metabolites through the intestine with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).

Pharmacokinetics in selected patient groups

In elderly patients (over 65 years of age) the excretion of amlodipine is slowed (T1/2 - 65 h) compared with young patients, but this difference has no clinical significance. In patients with hepatic insufficiency, lengthening T1/2 suggests that with prolonged use of cumulation drugs the body will be higher (T1/2 - up to 60 hours). Renal insufficiency does not have a significant effect on the kinetics of amlodipine. Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Amlodipine + lisinopril

Interaction between the active ingredients of the preparation Equator® is unlikely. AUC the time of reaching and the value of the maximum concentration, the half-lives do not undergo changes in comparison with the indices of each separately of the active substance. Eating does not affect the absorption of active ingredients.

Indications:

Essential hypertension (patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to lisinopril or other ACE inhibitors;

- Hypersensitivity to amlodipine or other dihydropyridine derivatives;

- Hypersensitivity to other components of the drug;

- Quincke's edema in the anamnesis, incl. Against the background of the use of ACE inhibitors;

- Hereditary or idiopathic angioedema;

- Hemodynamically significant stenosis of the aorta or mitral valve;

- Hypertrophic obstructive cardiomyopathy;

- Severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- Cardiogenic shock;

- Unstable angina (with the exception of Prinzmetal angina);

- Heart failure after acute myocardial infarction (within the first 28 days);

- Pregnancy and lactation;

- Age to 18 years (effectiveness and safety not established).

Carefully:

Severe renal dysfunction, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, a condition after kidney transplantation, azotemia, hyperkalemia, primary, hyperaldosteronism, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency), ischemic heart disease, coronaryinsufficiency / weakness syndrome sinus node (pronounced bradycardia, tachycardia), CHF of non-ischemic etiology III-IV functional class by classification NYHA, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction), autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), oppression of bone marrow hematopoiesis, diabetes mellitus, diet with restriction of table salt, hypovolemic condition (including as a result of diarrhea, vomiting), advanced age, hemodialysis using high-permeability dialysis membranes with high permeability (AN69®).

Pregnancy and lactation:

Application during pregnancy and lactation

The use of Equator® is not recommended during pregnancy.

When diagnosing pregnancy, taking the drug. Equator® should be discontinued immediately.

Admission of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, kidney failure, Hyperkalemia, hypoplasia of the skull bones, intrauterine death). Data on the negative effects of the drug on the fetus in the case of use during the first trimester of pregnancy is not. For newborns and infants,which have undergone intrauterine exposure to ACE inhibitors, is recommended to be closely monitored for the timely detection of a pronounced decrease in blood pressure, oliguria, and hyperkalemia.

The safety of amlodipine during pregnancy is not established, so the use of amlodipine is not recommended during pregnancy.

Lizinopril penetrates the placenta and can be excreted in breast milk. There is no evidence that amlodipine is excreted in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk.

The use of Equator during breastfeeding is not recommended. If the drug is needed during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

Tablets of the drug Equator ® are taken orally, once a day, regardless of time drinking a sufficient amount of liquid.

The recommended dose is 1 tablet of the drug Equator® 1 time per day. Maximum daily dose - 1 tablet of Equator®.

At the beginning of therapy with Equator®, symptomatic arterial hypotension, which occurs more often in patients with impaired water-electrolyte balance, due to previous therapy with diuretics. Admission diuretikov should be discontinued 2-3 days before the start of therapy with the drug Equator®. In cases where the cancellation of diuretics is not possible, the initial dose of the preparation Equator® is 1/2 / tablets once a day, after taking it for several hours should be monitored patients due to the possible development of symptomatic arterial hypotension.

Patients with renal insufficiency

To determine the optimal initial and maintenance dose for patients with renal the insufficiency of the dose must be titrated and determined on an individual basis, applying separately lisinopril and amlodipine. Equator® is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively. During treatment with the drug Equator® it is necessary to control kidney function, potassium and sodium in the blood serum. In the event of a degraded function

kidneys, taking Equator® should be discontinued and replaced with lisinopril and amlodipine in adequate doses.

Patients with hepatic insufficiency

Excretion of amlodipine may be delayed in patients with impaired hepatic function. Clear recommendations on the dosage regimen in such cases are not established, therefore the preparation Equator® should be administered with caution in patients with hepatic insufficiency.

Elderly patients (over 65 years of age)

In clinical studies, age-related changes in efficacy or safety profile for amlodipine and lisinopril have not been observed. To determine the optimal maintenance dose, it is necessary to determine the dosing regimen individually, using separately lisinopril and amlodipine. Equator® is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg, respectively.

Side effects:

The incidence of adverse reactions in patients receiving the combined drug was not higher than in patients receiving one of the active substances. Adverse reactions corresponded to the previously obtained data on amlodipine and / or lisinopril.Adverse reactions were mild, transient and rarely required the withdrawal of treatment. The most common adverse reactions with the combination of drugs were: headache (8%), cough (5%), dizziness (3%).

The frequency of adverse reactions is given separately for lisinopril and amlodipine.

The data are presented according to the system-organ classes in accordance with the classification MedDRA and with the following frequency: very often (> 1/10); often (from> 1/100 to <1/10); infrequently (from> 1/1 000 to <1/100); rarely (from> 1/10 000 to <1/1 000); very rarely (<1/10 000); frequency is unknown (can not be established based on available data).

Class of organ system MedDRA	Frequency	Undesirable effects of lisinopril	The undesirable effects of amlodipine
Disturbances from the hematopoietic and lymphatic system	Rarely	Inhibition of bone marrow hematopoiesis, Agranulocytosis, Leukopenia, neutropenia, Thrombocytopenia, Hemolytic anemia, Anemia, Lymphadenopathy.	Thrombocytopenia
Immune system disorders	Rarely	Vasculitis, Positive reactions to antinuclear antibodies	Hypersensitivity
Disorders from the metabolism and nutrition	Rarely	Hypoglycaemia	Hyperglycaemia
Mental disorders	Infrequently	Change in mood, sleep disorders	Sleep disturbance, mood changes
Mental disorders	Rarely	Disorders of the psyche
Disturbances from the nervous system	Often	Dizziness, headache	Drowsiness, dizziness, headache
	Infrequently	Systemic dizziness, paresthesia, dysgeusia	Syncope, tremor, dysgeusia, hypesthesia, paresthesia
	Rarely		Peripheral Neuropathy
Disturbances on the part of the organ of sight	Infrequently		Visual disturbances
Violations from the organ of hearing and labyrinth	Infrequently		Noise in ears
Heart Disease	Often Infrequently	Myocardial infarction, tachycardia, heart palpitations	Cardiopalmus
Heart Disease	Rarely		Myocardial infarction, ventricular tachycardia, atrial fibrillation, arrhythmia
Disorders from the vascular system	Often Infrequently	Orthostatic hypotension Violations of cerebral circulation, Raynaud's syndrome	Hyperemia of the skin
	Rarely		Vasculitis
Disturbances from the respiratory system, chest and mediastinal organs	Very infrequent Very rarely	Cough Rhinitis Bronchospasm, allergic alveolitis / eosinophilic pneumonia, sinusitis	Disnea, rhinitis Cough
Infringements from digestive systems	Often Infrequently	Diarrhea, vomiting Abdominal pain, nausea, indigestion	Abdominal pain, nausea Vomiting, indigestion, change in the rhythm of bowel movements, dry mouth
	Rarely	Dry mouth
	Rarely	Pancreatitis, angioedema	Pancreatitis, gastritis, gingival hyperplasia
		intestines
Infringements from liver and bile excretory ways	Rarely	Liver failure,	Hepatitis, jaundice, cholestasis
		hepatitis, cholestatic
		jaundice
Infringements from skin and subcutaneous fatty tissue	Infrequently	Allergic reactions angioedema face, limbs, lips, tongue, vocal folds and / or larynx, skin rash, itchy skin	Alopecia, skin rash purple, discoloration skin, increased sweating, itching
Infringements from skin and subcutaneous fatty tissue	Rarely	Psoriasis, urticaria rash, alopecia
	Rarely	Toxic epidermal necrolysis, Stevens- Johnson, multiforme erythema. Vulgar pemphigus, increased sweating.	The erythema multiforme, angioedema, urticaria rash
Infringements from musculoskeletal	Infrequently		Arthralgia, myalgia, convulsions in muscles, back pain
systems and connective tissue
Infringements from kidney and urinary tract	Often	Impaired renal function
	Infrequently		Upset, nocturia, increased frequency of urination
	Rarely	Acute renal failure, uremia
	Rarely	Oliguria / anuria
Infringements from reproductive system and dairy glands	Infrequently	Impotence	Impotence, gynecomastia
Infringements from reproductive system and dairy glands	Rarely	Gynecomastia
General (system) and local reactions	Often		Peripheral edema, increased fatigue
General (system) and local reactions	Infrequently	Increased fatigue, asthenia	Pain in the chest, pain, malaise, asthenia
Infringements from laboratory indicators	Infrequently	Increase in concentration urea and creatinine in serum, hyperkalemia, increased activity of "liver" enzymes.	An increase in body weight, weight loss
	Rarely		An increase in body weight, weight loss
	Rarely	Reduction of hemoglobin and hematocrit, hyperbilirubinemia, hyponatremia
	Rarely		Increased activity of "liver" enzymes

Overdose:

Symptoms: Overdose can lead to excessive peripheral vasodilation with severe arterial hypotension, collapse, disturbance of water-electrolyte balance, renal failure, dyspnea, tachycardia, bradycardia, dizziness, anxiety, cough.

Treatment: symptomatic therapy, control of cardiac activity, blood pressure, diuresis and water-electrolyte balance, if necessary - its correction. With a pronounced decrease in blood pressure, the patient is given a horizontal position with raised legs; if necessary, intravenous infusion of 0.9% sodium chloride solution; if these measures did not lead to a sufficient result, a peripheral vasopressor (dopamine) may be required to maintain blood circulation. Intravenous administration of calcium gluconate can have a positive effect on the reverse development of effects caused by calcium channel blockade. If necessary, intravenous angiotensin II.

Because of the slow absorption of amlodipine in some cases, the stomach is washed, used Activated carbon.

Lizinopril is excreted by hemodialysis. Due to the strong connection of amlodipine with blood proteins, hemodialysis of amlodipine is ineffective.

Interaction:

Lisinopril

Substances affecting the potassium content :, potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), potassium-containing food additives, potassium-containing salt substitutes and any other drugs that lead to an increase in potassium in the blood serum (eg, heparin) can lead to hyperkalemia when combined with ACE inhibitors, especially in patients with acutely insufficiency, and other kidney diseases in the anamnesis. When prescribing a drug that affects the potassium content, concomitantly with lisinopril, the potassium content in the blood serum should be monitored. Therefore, the simultaneous appointment should be carefully justified and carried out with extreme caution and regular monitoring of both the potassium content in the blood serum and the function of the kidneys.

Potassium-sparing diuretics can be taken together from preparation Equator® only under the condition of careful medical supervision.

Diuretics: If a diuretic is prescribed to a patient receiving Equator®, the antihypertensive effect, as a rule, increases. Simultaneous application should be to conduct with care. Lisinopril softens the potassium -uretic effect of diuretics.

Other antihypertensive drugs: simultaneous administration of these drugs can enhance the antihypertensive effect of the drug Equator®. Simultaneous reception with nitroglycerin, other nitrates or vasodilators can lead to a marked decrease in blood pressure.

Tricyclic antidepressants / antipsychotics / general anesthetics / narcotic analgesics: Simultaneous administration with ACE inhibitors can lead to a marked decrease in blood pressure.

Ethanol enhances the antihypertensive effect.

Allopurinol, procainamide, cytostatics or immunosuppressants, (systemic glucocorticosteroids) may lead to an increased risk of developing leukopenia when used concomitantly with ACE inhibitors.

Antacids and colestramine with simultaneous administration with ACE inhibitors reduce the bioavailability of the latter.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors; it is necessary to carefully monitor the achievement of the desired effect.

Hypoglycemic preparations: while concurrent administration of ACE inhibitors and hypoglycemic drugs(insulin and hypoglycemic agents for oral administration) may increase the likelihood of lowering blood glucose and the risk of hypoglycemia. This phenomenon is most often observed during the first week of combined treatment and in patients with renal insufficiency.

Non-steroidal anti-inflammatory drugs (NSAIDs): long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g / day, can reduce the antihypertensive effect of ACE inhibitors. The additive effect of NSAIDs and ACE inhibitors is manifested in an increase in serum potassium levels and can lead to impaired renal function. These effects are usually reversible. It is very rare to develop acute renal failure, especially in elderly and dehydrated patients.

Lithium preparations: the elimination of lithium can be slowed down during simultaneous administration with ACE inhibitors and therefore, the concentration of lithium in serum should be monitored during this period. When combined with lithium preparations, it is possible to intensify the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Preparations of gold: while simultaneous use of ACE inhibitors and gold preparations (sodium aurotomy malate) intravenously, a symptom complex including facial flushing, nausea, vomiting and arterial hypotension is described.

Amlodipine

Inhibitor inhibitors CYP3A4: studies among elderly patients have shown that diltiazem inhibits the metabolism of amlodipine, probably through CYP3A4 (plasma concentration increases by almost 50% and the effect of amlodipine increases). It is impossible to exclude the possibility that stronger inhibitors of the isoenzyme CYP3A4 (those. ketoconazole, itraconazole, ritonavir) may increase the serum amlodipine concentration to a greater extent than diltiazem. Simultaneous use should be carried out with caution.

Inductors of isoenzyme CYP3A4: simultaneous use with antiepileptic by means (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidon), rifampicin, herbal preparations containing St. John's Wort {Hypericum perforatum), can lead to a decrease in the concentration of amlodipine in the blood plasma. Clinical control with possible correction of amlodipine dose during treatment with isoenzyme inducers CYP3A4 and after their cancellation.Simultaneous use should be carried out with caution.

As a monotherapy amlodipine well combined with thiazide and loop diuretics, agents for general anesthesia, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacid preparations (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine , non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration. Amlodipine has no significant effect on the pharmacokinetics of ethanol.

Calcium preparations can reduce the effect of blockers of "slow" calcium channels. Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

It is possible to reduce the antihypertensive effect of the Equator® preparation with simultaneous administration with estrogenic agents, adrenostimulants.

Procainamide, quinidine and other drugs that extend the interval QT, can contribute to its considerable elongation.

Special instructions:

Arterial hypotension

A marked decrease in blood pressure with the development of clinical symptoms can be observed in patients with a decrease in the volume of circulating blood and / or sodium content due to diuretics, fluid loss or other reasons, for example, increased perspiration, prolonged vomiting and / or diarrhea. Preferably, the recovery of fluid and / or sodium loss is performed prior to the initiation of therapy with the Equator® preparation.

It is necessary to monitor BP after taking the initial dose. Similar conditions apply to patients with ischemic, heart disease or cerebrovascular disease, in whom a marked decrease in blood pressure can lead to myocardial infarction or stroke.

Aortic and mitral stenosis

Like all vasodilators, Equator® should be administered with caution to patients with obstruction of the left ventricular outflow tract and stenosis mitral valve.

Impaired renal function

In some patients with arterial hypertension without pronounced manifestations of renovascular diseases, an increase in the concentration of serum creatinine and urea was observed, in most cases minimal or transient, more pronounced with concurrent administration of an ACE inhibitor and a diuretic.This is most typical for patients with a history of kidney disease.

To determine the optimal maintenance dose, the dosage regimen should be determined individually, using separately lisinopril and amlodipine, with simultaneous monitoring of kidney function. Equator® is indicated only to those patients, in which the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 and 5 mg, respectively.

In the case of a decrease in kidney function, the preparation of Equator® should be discontinued and replaced by monotherapy with drugs in adequate doses. In addition, a dose reduction or elimination of diuretics may be required.

Angioedema

Angioedema of the face, extremities, lips, tongue, vocal folds and / or larynx was recorded in patients taking ACE inhibitors, including lisinopril. In these cases, the preparation of Equator® should be discontinued immediately and the patient should be carefully monitored until the symptoms disappear completely.

Edema of the face, lips and extremities usually passes by itself, nevertheless, for reduce the severity of symptoms should use antihistamines. Angioedema, accompanied by swelling of the larynx, can lead to death.If you detect edema of the tongue, pharynx or larynx, which are the cause of airway obstruction, emergency measures should be urgently started. The proper measures include: the use of 0.1% epinephrine (adrenaline) solution subcutaneously in a dose of 0.3 to 0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines and simultaneous monitoring of life- important functions.

Patients taking ACE inhibitors rarely had angioneurotic edema of the intestine. These patients complained of abdominal pain (with or without nausea and vomiting); in some cases of a previous angioedema, the face was not observed, and the activity of C-1 esterase was within normal limits. Angioedema of the intestine is diagnosed by computer tomography of the gastrointestinal tract, or after ultrasound, or in surgical intervention; symptoms disappeared after discontinuation of the ACE inhibitor. When performing differential diagnosis of abdominal pain in patients taking ACE inhibitors, you should also consider angioedema of the intestine.

Anaphylactic reactions in patients on hemodialysis

In patients who underwent hemodialysis through a polyacrylonitrile membrane (eg, AN-69®) and who simultaneously received ACE inhibitors, cases of anaphylactic shock have been reported, so it is necessary to avoid this combination. Patients are recommended to use either another type of dialysis membrane, or an antihypertensive drug of another pharmacotherapeutic group.

Anaphylactic reactions in patients during apheresis of low-density lipoproteins (LDL)

Rarely in patients who received ACE inhibitors during the apheresis of LDL with dextran sulfate, life-threatening anaphylactic reactions developed. Such reactions were prevented by abolishing the administration of ACE inhibitors prior to each apheresis procedure.

Desensitization from aspen or bee venom

Anaphylactic reactions developed in patients who took ACE inhibitors with desensitization of Hepaticoptera (eg, wasps or bees), such life-threatening situations can be avoided with the timely withdrawal of ACE inhibitors.

Effects on the liver

In rare cases, the administration of ACE inhibitors was accompanied by a syndrome,which began with cholestatic jaundice or hepatitis and grew into fulminant liver necrosis and, in several cases, resulted in death. The mechanism of this syndrome is unclear. Patients who receive Equator® and who develop jaundice or have an increase in activity of "liver" enzymes should cancel the drug, followed by monitoring their condition.

Liver failure

In patients with impaired hepatic function, the half-life of amlodipine is longer. At the moment, recommendations on the dosage regimen have not been developed, and therefore this medication should be administered with caution, having previously determined the expected benefit and the potential risk of treatment.

Neutropenia / agranulocytosis

In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after the withdrawal of the ACE inhibitor. Equator® should be used with extreme caution in patients with systemic connective tissue diseases, with immunosuppressive therapy,during treatment with allopurinol or procainamide or a combination of these aggravating factors, especially in the presence of a previous impairment of kidney function. Some of these patients developed serious infectious diseases, in which, in several cases, no response to antibiotic treatment was received. Periodically, in such patients during the treatment with the Equator® drug, it is recommended to conduct laboratory tests (blood count with calculating the leukocyte formula), and also to warn them about the need to report the appearance of the first signs of an infectious disease.

Cough

Cough was often recorded during the use of ACE inhibitors. As a rule, cough is unproductive, persistent and stopped after the drug was discontinued. With a differential diagnosis of cough, one must also consider the cough caused by the use of ACE inhibitors.

Surgery / general anesthesia

Patients undergoing extensiveoperative intervention or during general anesthesia with drugs leading to hypotension, lisinopril can block the formation of angiotensin II after compensatory release of renin.If arterial hypotension develops, probably as a result of the above mechanism, it is possible to correct the increase in the volume of circulating blood.

Elderly patients

Older patients with impaired renal function should be corrected for the dose of the drug Equator®.

Hyperkalemia

In some patients who received ACE inhibitors, an increase in the content potassium in the blood serum. The risk group for the development of hyperkalemia is patients with renal failure, diabetes, acute cardiac insufficiency, dehydration, metabolic acidosis or with simultaneous intake of potassium-sparing diuretics, potassium-containing food additives, potassium-containing salt substitutes or any other drugs that lead to an increase potassium content in serum (eg, heparin). If it is necessary to simultaneously take the above drugs, you need to monitor the content of potassium in the blood serum.

Patients with low body weight, patients of low growth and patients with severe a violation of liver function may require a dose reduction.

Equator® does not have any adverse effect on the metabolism and lipids of blood plasma and can be used in the treatment of patients with bronchial asthma, sugar diabetes and gout.

During the treatment, it is necessary to control the mass of the bodies with observation by the dentist (for prevention of soreness, bleeding and gingival hyperplasia).

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

The use of Equator® can affect the ability to drive vehicles and complex mechanisms. Predominantly at the beginning of treatment, transient arterial hypotension and dizziness may occur. Therefore, at the beginning of treatment, it is recommended to avoid driving vehicles, working with mechanisms and performing other work requiring increased concentration of attention.

Form release / dosage:

Tablets, 5 mg + 10 mg.

Packaging:10 tablets in a blister of white PVC foil / polyethylene / PVDC and lacquered hard aluminum foil. 1, 2, 3 or 6 blisters in a cardboard box with the attached instructions for use.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-002321

Date of registration:08.12.2011

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER-RUS, CJSC Russia

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp20.03.2014

Illustrated instructions

Instructions

Equator® (Ekvator®)