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

Active substances: amlodipine besylate 6.94 mg (equivalent to 5.00 mg of amlodipine), lisinopril dihydrate 21.76 mg (equivalent to 20.00 mg of lisinopril);

Excipients: cellulose microcrystalline (type 101) - 181.08 mg, microcrystalline cellulose (type 12) - 173.28 mg, sodium carboxymethyl starch (type A) - 8.00 mg, magnesium stearate - 2.00 mg.

Description:

White or almost white, round, biconvex tablets with engraving “CF2” on one side.

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 - Angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to direct reduction of aldosterone release. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance (OPSS), arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some of the effects are explained by exposure to tissue renin-angiotensin-aldosterone system (RAAS).

With prolonged 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 heart failure, 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 in patients with diabetes mellitus and does not increase the incidence 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 andarterioles: with stenocardia reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for myocardium in oxygen. Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the supply of oxygen in 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 reduction in blood pressure for 24 hours (in the patient's "lying" and "standing" position). 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 conductance of the myocardium, does not cause a reflex increase in 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 effect 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 is not affects 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. The 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%. Eating does not affect absorption amlodipine.

Distribution

Most of the amlodipine, which is in the blood (95% -98%), binds to blood plasma proteins. Stam 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 amlodipine 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 "first pass" effect. Metabolites do not have significant pharmacological activity.

Excretion

The elimination consists of two phases, T1 / 2 of the final phase of 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, T1 / 2 prolongation suggests that with prolonged use, amlodipine cumulation in the body will be higher (T1/2 - before 60 hours). Renal failure does not significantly affect 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 individual active substance. Food intake does not affect the absorption of active substances.

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 stenosis of the single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, liver dysfunction, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency), ischemic disease heart, coronary insufficiency, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), chronic heart failure non-ischemic etiology (CHF) 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 conditions (including as a result of diarrhea, vomiting), elderly age, hemodialysis with high-permeability dialysis membranes with high permeability (AN69®).

Pregnancy and lactation:

The use of Equator® is not recommended during pregnancy.

When diagnosing pregnancy, taking Equator® should be stopped 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, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal 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 who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked 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 breast-feeding is not recommended.

If the drug is needed during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake. The recommended dose is one tablet of the Equator® daily. The maximum daily dose is one tablet of the Equator® preparation.

Patients with renal insufficiency

To determine the optimal initial and maintenance dose for patients with renal insufficiency, the dose should be titrated and determined individually, 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 20 and 5 mg, respectively.During treatment with Equator®, it is necessary to monitor kidney function, potassium and sodium in the blood serum. In case of impaired renal function, the preparation of 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 20 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).

System class bodies MedDRA		Frequency	Undesirable effects of lisinopril		The undesirable effects of amlodipine
Violations from		Highly	Oppression		Thrombocytopenia
side of the hematopoietic and lymphatic system		rarely	bone marrow hematopoiesis, Agranulocytosis, Leukopenia, neutropenia, Thrombocytopenia, Hemolytic anemia, Anemia, Lymphadenopathy.
Violations from		Highly	Vasculitis,		Increased
the immune side		rarely	A positive test for		sensitivity
systems			antinuclear antibodies
Disorders from the metabolism and nutrition		Highly rarely	Hypoglycaemia		Hyperglycaemia
Mental		Infrequently	Changing the mood,		Insomnia, unusual
disorders			sleep disorders		dreams, mood changes, increased excitability, depression, anxiety.
		Rarely	Disorders of the psyche		Apathy, agitation.
Violations from the sides of the nervous system		Often	Dizziness, headache, drowsiness.		Drowsiness, dizziness, headache.
		Infrequently	Systemic dizziness, paresthesia, dysgeusia, convulsive twitching of the muscles of the extremities and lips.		Syncope, tremor, dysgeusia, hypesthesia, paresthesia.
		Rarely	Confusion of consciousness		Migraine
		Highly rarely			Peripheral neuropathy, ataxia, amnesia, parosmia.
Disturbances on the part of the organ of sight		Infrequently			Visual disturbances (diplopia, accommodation disorder), xerophthalmia, conjunctivitis, pain in the eyes.
Violations from the organ of hearing and labyrinth		Infrequently			Noise in ears
Heart Disease		Often Infrequently Rarely Highly rarely	Myocardial infarction, violation of atrioventricular conduction, bradycardia, tachycardia, heart palpitations, worsening of the course of CHF,chest pain.		Cardiopalmus Exacerbation of the course of CHF. Myocardial infarction, ventricular tachycardia, fibrillation auricles, arrhythmia.
Violations from hand vascular		Often	The pronounced decrease AD, orthostatic hypotension		Hyperemia of the skin
systems
		Infrequently	Disturbance of the cerebral blood circulation, Raynaud's syndrome		The pronounced decrease AD, orthostatic hypotension.
		Highly rarely			Vasculitis
Disturbances from the respiratory system, chest and mediastinal organs		Often Infrequently Rarely Highly rarely	Dry cough Rhinitis Dyspnea Bronchospasm, allergic alveolitis / eosinophilic pneumonia, sinusitis		Disneve, rhinitis, nosebleeds. Cough
Violations from hand digestive systems		Often	Diarrhea, vomiting		Pain in the abdomen, nausea.
		Infrequently	Pain in the abdomen, nausea, disorder digestion.		Vomiting, indigestion, constipation or diarrhea, dryness in mouth, anorexia, thirst.
		Rarely	Dry mouth		Increased appetite.
		Highly rarely	Pancreatitis, intestinal angioedema		Pancreatitis, gastritis, gingival hyperplasia.
Violations from side of the liver and bile excretory ways		Highly rarely	Hepatic insufficiency, hepatitis, cholestatic jaundice		Hepatitis, jaundice, cholestasis
Violations from the skin and subcutaneous fat cellulose		Infrequently	Allergic reactions / angioedema face, limbs, lips, language, vocal folds and / or larynx, cutaneous		Skin rash, purpura, itching, xeroderma.
		Rarely Highly rarely	rash, skin itch, photosensitization. Psoriasis, urticaria rash, alopecia Toxic epidermal necrolysis, Stevens-Johnson syndrome, multiform erythema. Vulgar pemphigus, increased sweating, pseudolymphoma of the skin *		Dermatitis. Multiform erythema, angioedema, urticaria rash, increased sweating, "cold sweats," alopecia, discoloration of the skin.
Violations from side of osteo- muscular systems and connective fabrics		Infrequently			Arthralgia, myalgia, muscle cramps, pain in the back, arthrosis.
		Rarely	Atrialgia, myalgia, arthritis.		Myasthenia gravis.
Violations from the kidneys and urinary tract ways		Often	Function violation kidney.
		Infrequently			Disorder urination, nocturia, increase frequency of urination
		Rarely	Acute renal
		Highly rarely	insufficiency, uremia. Oliguria / anuria.
Violations from hand reproductive systems and mammary glands		Infrequently	Impotence		Impotence, gynecomastia
		Rarely	Gynecomastia
General (systemic) and local reactions		Often			Peripheral edema, increased fatigue
		Infrequently	Increased fatigue, asthenia		Pain in the chest, pain, malaise, asthenia
Violations from hand laboratory indicators		Infrequently	Increase serum urea and serum creatinine concentrations		An increase in body weight, decrease in body weight.
		Rarely Highly	blood, hyperkalemia, increased activity of "hepatic" enzymes. Reduction of hemoglobin and hematocrit, erythropenia, hyperbilirubinemia, hyponatremia.		Increased activity
	rarely			"hepatic" enzymes

* The development of a complex symptom complex that may include all or some of the following symptoms has been reported: fever, vasculitis, myalgia, arthralgia / arthritis, positive antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity or other changes from the skin.

Overdose:

Amlodipine

Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, the appointment of activated charcoal, maintenance of cardiovascular function, control of the functions of the cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, monitoring the volume of circulating blood (bcc) and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); with the purpose of elimination of consequences of blockade of calcium channels - intravenous introduction of calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, delay urination, constipation, anxiety, increased irritability.

Treatment: gastric lavage, reception of activated charcoal, giving to the patient horizontal position with raised legs, replenishment of BCC - intravenous injection of plasma-substituting solutions, symptomatic therapy,control functions of the cardiovascular and respiratory systems, bcc, urea, creatinine and electrolytes in blood serum, as well as diuresis. Lisinopril can be removed from the body by hemodialysis.

Interaction:

Lisinopril

Substances affecting the content of potassium: potassium-sparing diuretics (for example, spironolactone, amiloride and triamterene), potassium-containing dietary supplements, potassium-containing salt substitutes and any other drugs that lead to an increase in serum potassium (for example, heparin) can lead to hyperkalemia when combined with ACE inhibitors, especially in patients with renal insufficiency and other kidney disease 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 with Equator® only ifcareful medical supervision.

Diuretics: In the case of diuretic administration to a patient receiving Equator®, the antihypertensive effect, as a rule, increases. Simultaneous use should be carried out with caution. 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 colstiraamine 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 drugs: with simultaneous administration of ACE inhibitors and hypoglycemic drugs (insulin and hypoglycemic agents for oral administration) may increase the likelihood of a decrease in 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) (including selective inhibitors of cyclooxygenase-2 (COX-2)): 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 suppresses the metabolism of amlodipine, probably through isoenzyme CYP3A4 (concentration in plasma / serum increases by almost 50% and the effect of amlodipine increases). It is impossible to exclude the possibility that more potent inhibitors of the isoenzyme CYP3A4 (eg, 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 drugs (eg, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort, can lead to a decrease in the concentration of amlodipine in the blood plasma. Control is shown 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-adrenoblockers, ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacid preparations (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine, nonsteroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration.

It is possible to enhance the anti-anginal and antihypertensive effect of BCCC when combined with thiazide and "loop" diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates, as well as enhance their antihypertensive effects when combined with alpha-adrenoblockers, neuroleptics.

A single dose of 100 mg sildenafil in patients with essential hypertensionhas an effect on the pharmacokinetics parameters of amlodipine.

Repeated use of amlodipine in a dose of 10 mg and atorvastatin in a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin. Antiviral drugs (ritonavir) increase plasma concentrations of BCCI, incl. amlodipine.

Neuroleptics and isoflurane - increased antihypertensive action of dihydropyridine derivatives.

Amlodipine does not significantly affect the pharmacokinetics ethanol.

Calcium preparations can reduce the effect of blockers of "slow" calcium channels. When combined use of amlodipine with lithium preparations possibly increased manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not cause significant changes in pharmacokinetics cyclosporine.

Does not affect the serum concentration of digoxinand its renal clearance.

Has no significant effect on the action warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.

It is possible to reduce the antihypertensive effect of the Equator® preparation when used simultaneously with estrogen, sympathomimetics.

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

In studies in vitro Amlodipine does not affect the binding to blood proteins of digoxin, phenytoin, warfarin and indomethacin.

Reception of amlodipine with grapefruit juice is not recommended, as in some patients this can lead to an increase in the bioavailability of amlodipine, resulting in increased its antihypertensive effect.

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 for other reasons, for example, increased perspiration, prolonged vomiting and / or diarrhea. It is necessary that the restoration of loss fluid and / or sodium was performed prior to the initiation of therapy with Equator®.

It is necessary to monitor BP after taking the initial dose. Similar states refer to patients with ischemic heart disease or cerebrovascular diseases in which a pronounced 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 of the 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, it is necessary to determine the dosage regimen individually, using separately lisinopril and amlodipine, with simultaneous monitoring of kidney function.Equator® is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 20 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 independently, however, to 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.Appropriate measures include the use of a 0.1% solution of epinephrine (epinephrine) subcutaneously in a dose of 0.3-0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines and simultaneous monitoring of life- important functions.

In patients taking ACE inhibitors, there was rarely an intestinal angioedema. These patients complained of abdominal pain (with nausea and vomiting or without them); in some cases of the previous angioedema, the face was not observed and the activity of C-1 esterase was within the normal range. Intestinal angioedema has been diagnosed by computed 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 intestinal angioedema.

Anaphylactic reactions in patients on hemodialysis

In patients who underwent hemodialysis through polyacrylonitrile membranes (for example, 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 withdrawal of an ACE inhibitor before each apheresis procedure.

Desensitization from aspen or bee venom

Sometimes in patients who took ACE inhibitors, when desensitizing the poison Hymenoptera (for example, wasps or bees) anaphylactic reactions developed. Such life-threatening situations can be avoided with the abolition of the ACE inhibitor before the desensitization procedure.

Exposure to the liver

In rare cases, the administration of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and developed 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 drug should be administered with caution, having previously estimated 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 with a combination of these aggravating factors, especially if there is an earlier impairment of kidney function.Some of these patients developed serious infectious diseases, in which a response to antibiotic treatment was not received in several cases. During treatment with the Equator® preparation, periodic monitoring of leukocytes (blood count with counting of the leukocyte formula) in such patients is necessary, as well as 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

In patients who undergo extensive surgery 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 undergo a dose adjustment, applying separately lisinopril and amlodipine.

Hyperkalemia

In some patients who received ACE inhibitors, an increase in the content potassium in the blood serum. Risk group for the development of hyperkalemia consists of patients with renal failure, diabetes, congestive heart failure, dehydration, metabolic acidosis or while receiving potassium-sparing diuretics, potassium-containing food additives, potassium-based salt substitutes or any other medications, leading to an increase of potassium in blood serum (e.g., heparin). If it is necessary to simultaneously take the above drugs, you need to monitor the potassium content in the blood serum.

Patients with reduced body weight, low growth patients and patients with severe liver dysfunction may need a dose reduction.

Ekvator® not exert any adverse effect on metabolism and plasma lipids and can be used to treat patients with asthma, diabetes and gout.

During treatment, it is necessary to control body weight and monitor the dentist (to prevent soreness, bleeding and gingival hyperplasia).

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

The preparation Equator® should be used with caution (the risk of a pronounced decrease in blood pressure and dizziness). 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 + 20 mg.

Packaging:For 10 tablets in a blister of PVC / PE / PVDC and lacquered hard aluminum foil. For 1, 3 and 6 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001645

Date of registration:12.04.2012

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

Manufacturer: & nbsp

GEDEON RICHTER, Plc. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp20.03.2014

Illustrated instructions

Instructions

Equator® (Ekvator®)