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

Oblong biconvex tablets white or almost white with a risk on both sides and engraved "CF" to the left of the risks and the number "5" to the right of the risks on one side.

Pharmacotherapeutic group:Antihypertensive agent combined (angiotensin-converting enzyme (ACE) inhibitor + blocker of "slow" calcium channels)

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Equator® is a combined preparation containing active ingredients: amlodipine and lisinopril.

Amlodipine

The dihydropyridine derivative is a blocker of "slow" calcium channels (BCCC). It blocks "slow" calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels, rather than in cardiomyocytes).

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 the overall peripheral vascular resistance (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 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 attacks and "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 hypotensive effect. Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. When hypertension single dose provides a clinically significant decrease in blood pressure (BP) over 24 hours (with the patient "lying" and "standing").

Orthostatic hypotension with amlodipine is rare. Amlodipine does not cause a decrease in exercise tolerance, or a fraction of the left ventricular ejection. 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 therapy of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.

Patients with cardiovascular diseases (CCC) (including coronary atherosclerosis with single vessel damage and up to stenosis of 3 or more arteries, carotid atherosclerosis) who underwent myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or in patients with anginal pectoris use of amlodipine prevents the development of thickening of intima-media of carotid arteries, reduces the mortality from myocardial infarction, stroke, PTCA, aorto-coronary shunting; leads to a decrease in the number of hospitalizations for unstable angina and the progression of chronic heart failure (CHF); reduces the frequency of interventions aimed at restoring coronary blood flow.

Does not increase the risk of death or development of complications and deaths in patients with CHF (III-IV Functional class (FC) according to the classification of the New York Heart Association (NYHA)) on the background of therapy with digoxin, diuretics and ACE inhibitors.

In patients with CHF (III-IV functional class by classification NYHA) non-ischemic etiology in the use of amlodipine, there is a possibility of pulmonary edema.

Lisinopril

Lizinopril is an ACE inhibitor that prevents the conversion of angiotensin I into angiotensin I. Reducing angiotensin II leads to a direct reduction in the secretion of aldosterone. Lisinopril reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral resistance of blood vessels, blood pressure, preload and pressure in the pulmonary capillaries. In patients with chronic heart failure lisinopril increases the minute volume of blood and leads to an increase in the tolerance of the myocardium to the load. Lisinopril provides a more pronounced expansion of the arteries than the veins. Some of the effects of lisinopril are mediated by its effect on the tissue renin-angiotensin system. Prolonged use of it leads to a decrease in myocardial hypertrophy and the walls of arteries of resistive type.

Lizinopril improves myocardial blood supply in ischemia.In patients with chronic heart failure, the use of ACE inhibitors increases life expectancy; in patients with a history of myocardial infarction and without heart failure lisinopril slows the progression of left ventricular dysfunction.

The effect occurs within 1 hour after taking lisinopril inside. The maximum effect develops within 6-7 hours; the effect lasts for 24 hours. In patients with hypertension, the effect is observed during the first days after the start of treatment; a stable effect is achieved within 1-2 months of treatment. With a sharp reversal of lisinopril, no significant increase in blood pressure was noted. Lisinopril provides both a reduction in blood pressure and a decrease in albuminuria. In patients with hyperglycemia lisinopril helps restore the function of the damaged endothelium glomeruli. In patients with diabetes mellitus lisinopril does not affect the concentration of glucose in the blood; The use of lisinopril does not lead to an increase in the incidence of hypoglycemia.

Equator®

A combined preparation containing amlodipine and lisinopril, prevents the development of possible side effects caused by one of the active substances. For example, a blocker of "slow" calcium channels, causing the expansion of arterioles, can lead to a delay in sodium and fluid in the body, which, in turn, can lead to activation of the renin-angiotensin-aldosterone system. The ACE inhibitor blocks this process and normalizes the reaction to the salt load.

Pharmacokinetics:

Amlodipine

Suction: after ingestion amlodipine is well absorbed from the gastrointestinal tract (GIT). The average absolute bioavailability is 64-80%, Cmah in serum is observed after 6-12 hours. Equilibrium concentrations (Css) are achieved after 7-8 days of therapy. Food intake does not affect the absorption of amlodipine.

Distribution and binding to blood plasma proteins: the average volume of distribution is 21 l / kg body weight, indicating that most of the drug is in the tissues, and the smaller - in the blood. Most of the drug in the blood (97.5%) binds to blood plasma proteins. Amlodipine penetrates the blood-brain barrier.

Metabolism / excretion: amlodipine is subjected to a slow but active metabolism in the liver in the absence of a significant "primary passage" effect through the liver. Metabolites do not have significant pharmacological activity. The half-life period (T1 / 2) from the blood plasma varies from 35 to 50 h, which allows taking the medication once a day. T1 / 2 with repeated use - about 45 hours. About 60% of the ingested dose is excreted by the kidneys mainly in the form of metabolites, 10% - unchanged, and 20-25% - through the intestines 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

Elderly patients: in elderly patients (over 65 years of age) amlodipine withdrawal is slowed (T1 / 2 - 65 h) compared with young patients, however this difference has no clinical significance.

Patients with hepatic impairment: lengthening T1 / 2 in patients with liver failure suggests that with prolonged use, cumulation of the drug in the body will be higher (T1 / 2 - up to 60 hours).

Patients with renal insufficiency: renal failure does not have a significant effect on the kinetics of amlodipine.

Lisinopril

Suction

When taking lisinopril inside of the gastrointestinal tract, 25% of the active substance is absorbed. Absorption of lisinopril does not depend on food intake. The average level of absorption is 30%, bioavailability is 29%.

Distribution and binding to blood plasma proteins

The maximum concentration (Cmah) in the blood plasma is achieved within 6-8 hours after ingestion.

Lizinopril poorly binds to plasma proteins, poorly penetrates the blood-brain barrier.

Metabolism

Lizinopril does not undergo biotransformation in the body.

Excretion

The half-life is 12 hours.

Pharmacokinetics in selected patient groups

Patients with CHF

In patients with CHF, absorption and clearance of lisinopril are reduced. In this category of patients, the absolute bioavailability of lisinopril is reduced by about 16%.

Patients with renal insufficiency

Violation of kidney function leads to an increase AUC (the area under the concentration-time curve) and the half-life of lisinopril, but these changes become clinically significant only when the glomerular filtration rate (GFR) decreases below 30 ml / min / 1.73 m². With mild and moderate renal failure (creatinine clearance (CK) from 30 to 80 ml / min), the mean AUC increases by 13%, while in severe renal failure (SC from 5 to 30 ml / min), the mean value increases AUC in 4,5 times.

Patients with hepatic insufficiency

In patients with cirrhosis of the liver, the absorption of lisinopril is reduced (by approximately 30%), but the effect of the drug is increased (approximately 50%) compared to healthy volunteers due to reduced clearance.

Patients of advanced age (over 65 years)

In elderly patients, the concentration of lisinopril in the blood plasma and the area under the concentration-time curve are 2 times higher than in young patients.

Equator®

The interaction between the active ingredients of the drug Equator® is unlikely. Values AUC, FROMmah, time to reach Cmah, and also T1 / 2, do not undergo changes in comparison with the indices of each individual active substance. Eating does not affect the absorption of active ingredients. Long-term circulation of both active substances in the body allows you to take the drug once a day.

Indications:Arterial hypertension (in patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to lisinopril or any other ACE inhibitor.

- Hypersensitivity to amlodipine or any other dihydropyridine derivative.

- Hypersensitivity to any of the excipients.

- Angioedema in history, including in connection with the use of ACE inhibitors.

- Hereditary or idiopathic angioedema.

- Shock (including cardiogenic).

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

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

- Hemodynamically significant obstruction of the left ventricular outflow tract (for example, with severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis.

- Hemodynamically unstable heart failure after acute myocardial infarction.

- Simultaneous use with aliskiren and preparations containing aliskiren, in patients with diabetes mellitus and / or moderate or severe renal dysfunction (glomerular filtration rate (GFR) of less than 60 ml / min / 1.73 m² body surface area.

- Simultaneous use with angiotensin II receptor antagonists (APA II) in patients with diabetic nephropathy

- Pregnancy and the period of breastfeeding.

- Children under the age of 18 years (effectiveness and safety not established).

Carefully:

Aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency), coronary heart disease, coronary insufficiency, CHF of non-ischemic genesis of FC III-IV, acute myocardial infarction (also within 1 month after acute myocardial infarction), Prinzmetal angina, sinus node weakness syndrome (severe tachycardia or bradycardia), severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), intake of potassium-sparing diuretics , potassium preparations and salt substitutes based on potassium, hyperkalemia, hyponatremia, myelosuppression, diabetes mellitus, bilateral stenosis of the renal arteries, stenosis of the renal artery in patients with unity hydrochloric kidney, post-renal transplant,renal failure, azotemia, hemodialysis using membranes with high permeability, primary aldosteronism, a diet with salt restriction, conditions associated with a decrease in the volume of circulating blood (including vomiting and diarrhea), advanced age, liver failure, concomitant use with inhibitors or inducers isoenzyme CYP3A4, simultaneous use with preparations containing aliskiren, or angiotensin II receptor antagonists (increased risk of hypertension, hyperkalemia and renal failure with double blockade of RAAS), in patients of the Negroid race.

Pregnancy and lactation:

Pregnancy

The use of the drug Equator® is contraindicated during pregnancy.

Data on the use of Equator® in pregnant women are not available in the context of adequate controlled clinical trials. If pregnancy is diagnosed, immediately stop treatment with Equator®. Patients planning a pregnancy should consult a doctor to prescribe antihypertensive therapy with an established safety profile during pregnancy.

Amlodipine

The safety of amlodipine during pregnancy is not established, so its use in pregnancy is possible only if the benefit to the mother exceeds the risk for the fetus and the newborn.

Lisinopril

The use of ACE inhibitors in the 2-3 trimesters of pregnancy can lead to the death of the fetus and the newborn. It is recommended that careful monitoring of newborns and infants exposed to intrauterine exposure to ACE inhibitors be made to detect a significant reduction in blood pressure, oliguria and hyperkalemia in a timely manner. Perhaps the appearance of hypochlorism, hypoplasia of the facial bones, deformation of the bones of the face and skull, lung hypoplasia and abnormalities of kidney development in the child.

Women of childbearing age should apply effective methods of contraception in the treatment of lisinopril.

Lizinopril can penetrate the hematoplacental barrier. Treatment with lisinopril should not be started during pregnancy. Patients planning a pregnancy should consult a doctor to prescribe antihypertensive therapy with an established safety profile during pregnancy.

Breastfeeding period

Amlodipine

It is not known whether the amlodipine in breast milk. However, it is known that other BCCC derivatives of dihydropyridine penetrate breast milk.

Lisinopril

Data on the penetration of lisinopril into breast milk are absent.

Equator®

The use of Equator® during breastfeeding is contraindicated.

Dosing and Administration:

Inside, regardless of food intake. The recommended dose is one tablet of the Equator® preparation daily, at the same time each day, with plenty of water. The maximum daily dose is one tablet of the Equator® preparation.

Doses

Equator® is indicated only for those patients whose optimal maintenance dose of lisinopril and amlodipine is 10 mg and 10 mg, respectively. If necessary, dose adjustment amlodipine and lisinopril should be applied separately.

With the development of arterial hypotension at the beginning of therapy with the drug Equator®: with the development of arterial hypotension the patient should lie on his back, stop taking the drug and consult a doctor. Transient arterial hypotension usually does not require withdrawal of the drug, but the need to reduce the dose should be assessed.If it is necessary to select a dose, you should use medicines amlodipine and lisinopril apart.

If you find that you forgot to take the dose of the Equator® preparation, wait until the next dose and take the usual dose. Do not take a double dose to reimburse the missed dose.

Special patient groups

Patients with renal insufficiency

During therapy with Equator®, kidney function, as well as potassium and sodium in the serum, should be monitored. In case of impaired renal function, it is necessary to cancel the preparation of Equator® and to prescribe the therapy with correctly selected doses of individual components.

Patients with hepatic insufficiency

Possible delay in the excretion of amlodipine in patients with impaired liver function. Clear recommendations for the dose of the drug Equator ® in such cases are not established, so patients with violations of the liver drug should be administered with caution.

Children and adolescents (under 18 years of age)

The safety and efficacy of Equator® in children and adolescents have not been established.

Elderly patients (over 65 years of age)

Treatment of elderly patients should be done with caution.

Clinical studies have identified age-related changes in the efficacy or safety profile of amlodipine and lisinopril.

Side effects:

The incidence of adverse reactions in patients taking the combined drug did not exceed that of patients receiving one of the active substances. Adverse reactions corresponded to the data previously obtained for amlodipine and / or lisinopril. Adverse reactions were mild, transient and rarely required discontinuation of therapy. The most common adverse reactions with the combined drug were headache (8%), cough (5%) and dizziness (3%).

The frequency of adverse reactions is given separately for lisinopril and amlodipine. Below are the undesirable drug reactions (NLR) recorded during the separate use of amlodipine-1 and lisinopril-2.

The frequency of undesired reactions was determined as follows:

Very often: 1/10 cases (≥10%)

Frequently: 1/100 cases (≥1% and <10%)

Infrequently: 1/1000 cases (≥0.1% and <1%)

Rarely: 1/10000 cases (≥0.01% and <0.1%)

Very rarely: less than 1/10000 cases (<0.01%).

The frequency is unknown (the frequency could not be established based on the available data).

In each group, undesirable reactions are presented in order of decreasing severity.

Violations of the blood and lymphatic system

Reduction of hemoglobin^{2 (rarely)}, a decrease in hematocrit^{2 (rarely)}, oppression of bone marrow hematopoiesis^{2 (very rarely)}, leukopenia^{1.2 (very rarely)}, thrombocytopenia^{1.2 (very rarely)}, agranulocytosis^{2 (very rarely)}, hemolytic anemia^{2 (very rarely)}, neutropenia^{2 (very rarely)}, anemia^{2 (very rarely)}, lymphadenopathy^{2 (very rarely)}.

Immune system disorders

Allergic reactions^{1 (very rarely)}, autoimmune disorders^{2 (very rarely)}.

Disorders from the endocrine system

Syndrome of inadequate secretion of antidiuretic hormone^{2 (rarely)}.

Disorders from the metabolism and nutrition

Hyperglycaemia^{1 (very rarely)}, hypoglycaemia^{2 (very rarely)}.

Disorders of the psyche

Lability moods ^{1,2 (infrequently)}, sleep disorders^{2 (infrequently)}, hallucinations^{2 (infrequently)}, insomnia^{1 (infrequently)}, ^{anxiety1 (infrequently)}, depression^{1 (infrequently), 2 (frequency unknown)}, confusion^{1.2 (rare)}.

Disturbances from the nervous system

Dizziness^{1.2 (often)}, headache^{1.2 (often)}, drowsiness^{1 (often)}, vertigo^{2 (infrequently)}, paresthesia ^{1,2 (infrequently)}, dysgeusia^{1,2 (infrequently)}, faint ^{1 (infrequently), 2 (frequency unknown)}, tremor^{1 (infrequently)}, hypoesthesia^{1 (infrequently)}, parosmia^{2 (rarely)} (impaired sense of smell), hypertonic muscle^{1 (very rarely)}, peripheral neuropathy^{1 (very rarely)}, extrapyramidal disorders^{1 (frequency unknown)}.

Disturbances on the part of the organ of sight

Visual impairment (including diplopia)^{1 (often)}.

Hearing and balance disorders

Noise in ears^{1 (infrequently)}.

Ondestruction from the heart

Heart palpitations^{1 (often), 2 (infrequently)}, myocardial infarction^{1 (very} ^{rarely), 2 (infrequently)}, tachycardia^{2 (infrequently)}, ventricular tachycardia^{1 (infrequently)}, arrhythmia^{1 (infrequently)}, bradycardia^{1 (infrequently)}, atrial fibrillation^{1 (infrequently)}.

Vascular disorders

Orthostatic hypotension and related symptoms^{2 (often)}, "tides" of blood to the skin of the face^{1 (often)}, acute disturbance of cerebral circulation^{2 (infrequently)} (due to a marked decrease in blood pressure in groups of patients at increased risk), Raynaud's syndrome^{2 (infrequently)}, vasculitis^{1 (very rarely)}, hypotension^{1 (infrequently)}.

Disturbances from the respiratory system, chest and mediastinal organs Dyspnea^{1 (often)}, coughing^{1 (infrequently), 2 (often)}, rhinitis^{1,2 (infrequently)}, bronchospasm^{2 (very rarely)}, allergic alveolitis^{2 (very rarely)}, eosinophilic pneumonia^{2 (very rarely)}, sinusitis^{2 (very rarely)}.

Disorders from the gastrointestinal tract

Abdominal pain^{1 (often), 2 (infrequently)}, nausea^{1 (often), 2 (infrequently)}, dyspepsia^{1 (often), 2 (infrequently)}, change in the rhythm of defecation^{1 (often)}, diarrhea^{1.2 (often)}, constipation^{1 (often)}, vomiting^{1 (infrequently),} ^{2 (often)}, dry mouth ^{1 (infrequently),2( rarely)}, pancreatitis^{1.2 (very rarely)}, gastritis^{1 (very rarely)}, intestinal angioedema^{2 (very rarely)}, gingival hyperplasia¹ ^(highly ^rarely).

Disturbances from the liver and bile ducts

Hepatitis^{1 (very rarely)}, hepatitis (including hepatic-cellular or cholestatic)^{2 (very rarely)}, jaundice^{1.2 (very rarely)}, liver failure^{2 (very} ^rarely), increased activity of "hepatic" enzymes ^{1 (very rarely)}.

Disturbances from the skin and subcutaneous tissues

Alopecia ^{1 (infrequently), 2 (rarely)}, exanthema^{1 (infrequently)}, purple^{1 (infrequently)}, depigmentation of the skin^{1 (infrequently)}, hyperhidrosis^{1 (infrequently), 2 (very rarely)}, itchy skin^{1,2 (infrequently)}, rash^{1,2 (infrequently)}, hives^{1 (infrequently), 2 (rarely)}, psoriasis^{2 (rarely)}, erythema multiforme^{1.2 (very rarely)}, angioedema^{1 (very} ^{rarely), 2 (rarely)}, exfoliative dermatitis^{1 (very rarely)}, toxic epidermal necrolysis^{2 (very rarely)}, Stevens-Johnson syndrome^{1.2 (very rarely)}, angioedema^{1 (very rarely)}, photosensitivity^{1 (very rarely)}, vulgar pemphigus^{2 (very rarely)}, benign skin lymphadenosis *^{2 (very rarely)}, hypersensitivity / angioedema, swelling of the face, hands and feet, lips, tongue, glottis and / or larynx^{2 (rarely)}. (*: reported a symptomatic complex that may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia / arthritis, positive response to antinuclear antibodies (ANA), increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, skin rash , photosensitization or other changes from the skin).

Disturbances from musculoskeletal and connective tissue

Muscle cramps^{1 (often)}, swelling in the ankle^{1 (often)}, arthralgia^{1 (infrequently)}, myalgia^{1 (infrequently)}, backache^{1 (infrequently)}.

Disorders from the kidneys and urinary tract

Impaired renal function^{2 (often)}, upset urination^{1 (infrequently)}, nocturia^{1 (infrequently)}, frequent urination^{1 (infrequently)}, acute renal failure^{2 (rarely)}, uremia^{2 (rarely)}, oliguria^{2 (very rarely)}, anuria^{2 (very rarely)}.

Violations of the genitals and mammary gland

Gynecomastia^{1 (infrequently), 2 (rarely)},impotence ^{1,2 (infrequently)}.

General disorders and disorders at the site of administration

Edema^{1 (very often)}, increased fatigue^{1 (often), 2 (infrequently)}, asthenia^{1 (often), 2 (infrequently)}, chest pain^{1 (infrequently)}, pain^{1 (infrequently)}, malaise^{1 (infrequently)}.

Impact on laboratory and instrumental research results: increase in the concentration of creatinine and urea^{2 (infrequently)}, hyperkalemia^{2 (infrequently)}, hyperbilirubinemia^{2 (rarely)}, hyponatraemia^{2 (rarely)}, increased activity of "hepatic" enzymes^{2 (frequency is unknown)}, decrease or increase in body weight^{1 (infrequently)}.

If the flow of any of the above unwanted reactions deteriorates or a new undesired reaction occurs, not specified in this manual, you should see a doctor.

Overdose:

Amlodipine

Symptoms: marked decrease in blood pressure with 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 (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, elevating the position of the lower extremities, monitoring heart and lung performance, monitoring the volume of circulating blood and diuresis. To restore the vascular tone - the use of vasoconstrictor (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urine retention, constipation, anxiety, irritability.

Treatment: symptomatic therapy, infusion of 0.9% solution of sodium chloride and vasopressors (if possible), control of blood pressure, maintenance of water-electrolyte balance. It is possible to conduct hemodialysis (See "Special instructions - Hemodialysis").

Interaction:

Amlodipine

Contraindicated drug combinations

Dantrolene (intravenous administration)

In laboratory animals, cases of ventricular fibrillation with a lethal outcome and collapse on the background of verapamil and intravenous dantrolene were observed, accompanied by hyperkalemia. Due to the risk of hyperkalemia, simultaneous administration of "slow" calcium channel blockers, including amlodipine, in patients prone to malignant hyperthermia, as well as in the treatment of malignant hyperthermia, should be avoided.

Unrecommended combinations of drugs

Grapefruit juice

Taking amlodipine with grapefruit or grapefruit juice is not recommended, as in some patients the bioavailability of amlodipine may increase, which leads to an increase in the effects of lowering blood pressure.

Combinations of medicines that require special care when applied

Inductors of isoenzyme CYP3A4

Data on the influence of inducers of isoenzyme CYP3A4 on the pharmacokinetics of amlodipine are absent. Simultaneous reception of isoenzyme inducers CYP3A4 (for example, rifampicin, St. John's wort products) and amlodipine may lead to a decrease in plasma concentrations of amlodipine. Caution should be exercised when using the Equator® and isoenzyme inducers simultaneously CYP3A4.

Inhibitor inhibitors CYP3A4

Simultaneous reception of amlodipine and strong or moderate inhibitors CYP3A4 (protease inhibitors, for example, ritonavir, antifungal agents of the azole group, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. Therefore, monitoring of the clinical condition and dose adjustment of the Equator® preparation may be required.

Combinations of medicines that require caution when used

Simvastatin

Multiple admission of amlodipine at a dose of 10 mg in combination with simvastatin at a dose of 80 mg led to an increase in the exposure of simvastatin by 77% compared with simvastatin monotherapy.Thus, patients receiving amlodipine, should be taken simvastatin in a daily dose of not more than 20 mg.

Calcium preparations

Can reduce the effect of BCCI.

Lithium preparations

When BCCC is combined with lithium preparations (there is no data for amlodipine), the manifestation of their neurotoxicity may be enhanced (nausea, vomiting, diarrhea, ataxia, tremor, or tinnitus).

Baclofen

Increased antihypertensive effect. It is necessary to monitor blood pressure and kidney function, if necessary - adjust the dose of amlodipine.

Amifostine

It is possible to increase the antihypertensive effect of amlodipine.

Glucocorticosteroids

Reduction of antihypertensive action (fluid retention and sodium ions due to the action of corticosteroids).

Tricyclic antidepressants of antipsychotics

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Tacrolimus

With simultaneous use with amlodipine, there is a risk of increasing tacrolimus concentration in the blood plasma. In order to avoid the toxicity of tacrolimus when used simultaneously with amlodipine, the concentration of tacrolimus in the blood plasma of the patients should be monitored and the dose of tacrolimus corrected, if necessary.

Tasononemine: with simultaneous application amlodipine can increase the system exposure tasononemine in the blood plasma. In such cases, regular monitoring of the tasononemine in the blood and a dose adjustment if necessary.

Other interactions with amlodipine

For the treatment of hypertension amlodipine can be safely applied with thiazide diuretics, alpha-adrenoblockers, beta-blockers and ACE inhibitors. In patients with stable angina, simultaneous use of amlodipine with other antianginal drugs, such as nitrates long and short action, beta-blockers.

Probably, increased antianginal and antihypertensive action of BCCK with simultaneous use with thiazide and loop diuretics, ACE inhibitors. beta-blockers and nitrates, as well as enhancement of their antihypertensive action in the appointment with alpha-1-adrenoblockers and neuroleptics.

Amlodipine does not cause a negative inotropic effect. Nevertheless, some BCCI may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause lengthening of the interval QT (eg, amiodarone and quinidine).

Unlike other BCCI, there was no significant interaction of amlodipine (3rd generation BCCC) and NSAIDs, including indomethacin.

Securely assign amlodipine from oral hypoglycemic drugs. One-time reception sildenafil in a dose of 100 mg in patients with essential hypertension did not affect the pharmacokinetics of amlodipine. A joint multiple dose of amlodipine at a dose of 10 mg and atorvastatin in a dose of 80 mg led to an insignificant change in the pharmacokinetic parameters of atorvastatin in a state of equilibrium concentration.

Ethanol (drinks, containing alcohol): amlodipine does not have a significant effect on the pharmacokinetics of ethanol with a single and repeated application in a dose of 10 mg. Interaction Studies cyclosporine and amlodipine in healthy volunteers and in special groups of patients were not performed, except for patients after kidney transplantation. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporin to varying degrees to 40%.It is necessary to monitor the concentration of cyclosporine in patients after kidney transplantation.

With the simultaneous use of amlodipine and digoxin the renal clearance and serum digoxin concentration do not change.

With simultaneous application warfarin with amlodipine prothrombin time does not change.

When used simultaneously with cimetidine the pharmacokinetics of amlodipine does not change.

Amlodipine does not affect the degree of binding digoxin, phenytoin, warfarin and indomethacin with blood plasma proteins in vitro.

Aluminum and magnesium-containing antacids: a single administration of such antacids together with amlodipine does not significantly affect the pharmacokinetics of amlodipine.

Lisinopril

Contraindicated combinations of medicines

Aliskiren

Simultaneous administration of ACE inhibitors with aliskiren and aliskiren-containing preparations in patients with diabetes mellitus and / or moderate or severe renal dysfunction (GFR less than 60 mL / min / 1.73 m² surface area of the body) contraindicated.

The use of ACE inhibitors with angiotensin receptor antagonists II contraindicated patients with diabetic nephropathy.

Unrecommended combinations of drugs

Angiotensin II receptor antagonists (APA II)

In the literature it was reported that in patients with established atherosclerotic disease, chronic heart failure or diabetes with target organ damage, concurrent therapy with an ACE inhibitor and an ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RA AS. Double blockade (eg, with the combination of an ACE inhibitor with an APA II) should be limited separate cases with careful monitoring of kidney function, potassium and blood pressure.

Drugs katya, potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) or potassium-containing salt substitutes

Perhaps the development of hyperkalemia (with a possible fatal outcome), especially if the kidney function is impaired (additional effects associated with hyperkalemia). ACE inhibitors should not be used concomitantly with substances that increase the level of potassium in the blood plasma, except for cases of hypokalemia.The combination of lisinopril and the above remedies is not recommended. If, however, simultaneous application is shown, they should be used, observing safety precautions and regularly monitoring the potassium content in serum.

Lithium preparations

With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in serum lithium concentration and related toxic effects can be noted. The simultaneous use of lisinopril and lithium preparations is not recommended. If this therapy is necessary, a regular monitoring of the concentration of lithium in serum should be carried out.

Combinations of drugs that require extreme caution when used

Insulin and oral hypoglycemic agents

Epidemiological studies have shown that the combined use of ACE inhibitors and hypoglycemic agents (insulins, hypoglycemic agents for oral administration) can enhance their hypoglycemic action until the development of hypoglycemia. This effect, most likely, can be observed during the first weeks of simultaneous therapy, as well as in patients with impaired renal function. Baclofen

Strengthens the antihypertensive effect of ACE inhibitors.You should carefully monitor the level of blood pressure and, if necessary, adjust the dose of antihypertensive drugs.

Diuretics

In patients taking diuretics, especially those taking out fluid and / or salts, at the beginning of therapy with an ACE inhibitor, a significant reduction in blood pressure can be observed. The risk of developing antihypertensive effects can be reduced by eliminating the diuretic, replenishing the loss of fluid or salts before starting therapy with ACE inhibitors. With arterial hypertension in patients with prior therapy diuretics, which could lead to excessive elimination of fluid and / or salts, diuretics should be discontinued before the use of the Equator®.

The function of the kidneys (creatinine concentration) should be monitored in the first weeks of using the Equator®.

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ³3 g / day

Simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors.Simultaneous use of drugs with ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and closely monitor kidney function, both at the beginning of treatment and during treatment.

Estramustine, inhibitors mTOR (sirolimus, everolimus, tessirolimus), neutral endopeptidase inhibitors (omapatrilat, ilepatril, daglutryl, sacubitryl) Simultaneous use with ACE inhibitors is accompanied by an increased risk of developing angioedema.

DPP-4 inhibitors (glyptins)

Linagliptin, saxagliptin, sitagliptin, vildagliptin: when combined with ACE inhibitors, the risk of angioedema due to inhibition of dipeptidyl peptidase-4 activity increasesDPP-IV) glyptin.

Racecadotril (an enkephalinase inhibitor used to treat acute diarrhea)

With simultaneous use with ACE inhibitors, the risk of developing angioedema may increase.

Combinations of medicines, requiring caution when applying

Other antihypertensives (for example,, beta-adrenoblockers, blockers of "slow" calcium channels, diuretics) and vasodilators

It is possible to increase the antihypertensive effect of the drug. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates or other vasodilators, as this may further reduce blood pressure.

Antacids and cholestyramine

Simultaneous use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.

Tricyclic antidepressants, antipsychotics, general anesthetics, barbiturates, phenothiazine, ethanol

With joint admission, it is possible to intensify the action of lisinopril.

Sympathomimetics

Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors. Muscle relaxants

Simultaneous use of muscle relaxants with ACE inhibitors can lead to a marked decrease in blood pressure.

Preparations of gold

When using ACE inhibitors, including lisinopril, by patients receiving intravenously a gold preparation (sodium aurotomy malate), rare cases of nitrite reaction (a symptom complex including facial flushing, nausea, vomiting and arterial hypotension) have been described.

Co-trimoxazole (sulfamethoxazole and trimethoprim)

Increased risk of hyperkalemia.

Selective serotonin reuptake inhibitors (escitalopram, paroxetine, fluoxetine, sertraline)

With simultaneous application with SSRIs, it is possible to develop pronounced hyponatremia.

Allopurinol, procainamide, cytotoxic agents (5-fluorouracil, vincristine, docetaxel) Possible development of leukopenia.

Tissue activators of plasminogen (alteplase, reteplase, tenecteplase)

Increased risk of angioedema and simultaneous use with ACE inhibitors.

Special instructions:

When you go to the hospital, tell your doctor that you are taking Equator®.

When using Equator®, the warnings regarding its individual components should be taken into account, as shown below.

Associated with amlodipine

It is necessary to maintain dental hygiene and supervision at the dentist (to prevent soreness, bleeding and gingival hyperplasia).

In elderly patients, T1 / 2 may increase and the clearance of the drug may decrease. Dose changes are not required, but more careful monitoring of patients of this category is necessary.

The effectiveness and safety of the use of the Equator® preparation for hypertensive crisis have not been established.

Despite the absence of the "cancellation" syndrome in BCC, it is desirable to stop amlodipine treatment, gradually reducing the dose of the drug. Against the background of amlodipine in patients with chronic heart failure, Class III and IV NYHA non-ischemic origin, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

Impact on fertility

In some patients receiving blockers of "slow" calcium channels, reversible biochemical changes in the sperm head were found, which can be clinically significant in IVF. However, at present there is insufficient clinical data on the potential impact of amlodipine on fertility.In a preclinical study, undesirable effects on fertility in males were identified.

Associated with lisinopril

Symptomatic arterial hypotension

Most often, a significant reduction in blood pressure occurs with a decrease in the volume of circulating blood caused by the use of diuretics, a decrease in the amount of salt in the food, dialysis, diarrhea, or vomiting (see "Interaction with Other Drugs", "Side Effects"). In patients with chronic heart failure, in combination with renal insufficiency or without it, the development of symptomatic arterial hypotension is possible. It often develops in patients with severe heart failure, which is associated with the use of high doses of diuretics, hyponatremia or impaired renal function. Such patients need careful medical supervision (with careful selection of doses of lisinopril and diuretics). The same recommendations apply to patients with coronary heart disease and cerebrovascular insufficiency, when a rapid decrease in blood pressure can lead to the development of myocardial infarction or stroke.

Patients with a marked decrease in blood pressure should be given a horizontal position; If necessary, an infusion of 0.9% sodium chloride solution is performed. Transient hypotension is not a contraindication to taking the next dose of lisinopril.

In patients with chronic heart failure with normal or low blood pressure, the use of lisinopril may lead to a decrease in blood pressure; as a rule, this does not require the cessation of treatment. If arterial hypotension becomes symptomatic, it is necessary to evaluate the indications for a decrease in the dose of lisinopril or its withdrawal.

Patients with a risk of developing symptomatic arterial hypotension (patients on a salt-free diet or a diet with a low salt content) with or without hyponatremia, as well as in patients receiving high doses of diuretics, must compensate for the deviation (loss of water and salts) prior to treatment.

It is necessary to monitor the effect of the starting dose of lisinopril on blood pressure.

Acute myocardial infarction

It is recommended that a standard treatment (thrombolytics, acetylsalicylic acid, beta-blockers).

Possible simultaneous use of lisinopril with intravenous nitroglycerin or the use of transdermal nitroglycerin.

In patients with acute myocardial infarction and risk of further hemodynamic disorders, worsening of the condition after the administration of vasodilators, therapy with lisinopril should not begin. Such patients include persons with systolic blood pressure ≤ 100 mm Hg. Art. or cardiogenic shock. In patients with systolic blood pressure ≤ 120 mm Hg. Art. it is necessary to reduce the dose within the first 3 days after myocardial infarction. In patients with systolic blood pressure ≤ 100 mm Hg. Art. should reduce the maintenance dose up to 5 mg (or temporarily up to 2.5 mg). In patients with persistent arterial hypotension (systolic BP <90 mm Hg for 1 hour and longer) lisinopril should be canceled.

Impaired renal function

In patients with chronic heart failure, a significant reduction in blood pressure that occurs after the initiation of therapy with ACE inhibitors may lead to an aggravation of renal dysfunction. Cases of acute renal failure were reported.

In patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney, cases of an increase in the concentration of urea and creatinine in serum,associated with the use of ACE inhibitors; as a rule, these violations were transient and discontinued after the withdrawal of lisinopril. They were more common in patients with renal insufficiency.

Patients with acute myocardial infarction and significant renal dysfunction (with a serum creatinine concentration of> 177 μmol / L and / or proteinuria> 500 mg / day) lisinopril should not be appointed. With the development of impaired renal function against the background of treatment with lisinopril (creatinine clearance in the serum> 265 μmol / l or doubling it compared to the baseline), the possibility of lifting lisinopril should be considered.

Hypersensitivity, angioedema

In patients who received ACE inhibitors, including lisinopril, rare cases of angioneurotic edema of the face, extremities, lips, tongue, epiglottis and / or larynx that could occur during any treatment period were recorded. In such cases, you must immediately cancel lisinopril; Monitoring of patients should be carried out until the symptoms disappear completely. Usually cases of angioedema of the face and lips are temporary and do not require anytreatment; it is possible to prescribe antihistamines.

Angioneurotic edema of the larynx can lead to death. An angioneurotic edema of the tongue, epiglottis or larynx can lead to secondary airway obstruction, therefore, an appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) at a concentration of 1: 1000 sc.) Must be started immediately and / or measures taken to ensure the patency respiratory tract.

In rare cases, on the background of therapy with ACE inhibitors, angioedema of the intestine developed. In this case, patients had abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases, without prior angioedema and at a normal level Cl-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of developing angioedema of the intestine during differential diagnosis.

In patients with angioedema, which is not associated with the administration of ACE inhibitors, the use of ACE inhibitors may be associated with a higher risk of developing angioedema (see Contraindications).

Anaphylactic reactions, associated with desensitization of the venom of Hymenoptera insects

There are reports of very rare cases that threaten the life of anaphylactic reactions that developed in patients taking ACE inhibitors during desensitization by the venom of Hymenoptera. To prevent such cases, temporarily discontinue ACE inhibitors before desensitizing.

Hemodialysis

Anaphylactic reactions have also been reported in patients undergoing hemodialysis using membranes with high permeability (for example, AN69), who were simultaneously prescribed ACE inhibitors. Such a group of patients should consider the possibility of using other membranes for dialysis or other antihypertensive drugs.

Cough

The use of ACE inhibitors may be associated with a cough. The dry cough that lasts for a long time tends to disappear after the withdrawal of the ACE inhibitor.When conducting differential diagnosis, one should take into account the possibility of the appearance of a cough associated with the use of ACE inhibitors.

Surgery / general anesthesia

The use of drugs that lower blood pressure during extensive surgery or general anesthesia can lead to inhibition of the formation of angiotensin II in response to the compensatory secretion of renin. A significant reduction in blood pressure, which is considered as the result of this effect, can be controlled by reducing the volume of circulating blood.

Patients taking ACE inhibitors should inform their surgeon / anesthesiologist about this before performing surgery (including dental interventions).

The content of potassium in the blood serum

There have been reported cases of hyperkalemia.

Risk factors for hyperkalemia include renal failure, diabetes mellitus, and simultaneous use of potassium-sparing diuretics (spironolactone, triamterene, as well as amiloride), as well as potassium and salt substitutes based on potassium, especially in patients with impaired renal function.

If it is necessary to simultaneously use lisinopril and the above drugs, you should be careful and regularly monitor the potassium content in the serum.

Double blockade of RAAS

It is proved that simultaneous administration of ACE inhibitors. blockers of angiotensin II receptors or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Thus, it is not recommended to prescribe ACE inhibitors, angiotensin II receptor blockers or aliskiren for a double blockade of the RAAS.

If there are absolute indications for a double blockade of RAAS, then it should be performed under the close supervision of a specialist with frequent monitoring of blood pressure, kidney function and electrolyte content.

Simultaneous use of ACE inhibitors with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus and / or with moderate or severe renal failure (GFR less than 60 mL / min / 1.73 m² body surface area) and is not recommended in other patients.

The simultaneous use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabeticNephropathy and is not recommended in other patients.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of the administration of ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. Caution should be given to the preparation of Equator® in patients with systemic connective tissue diseases, when immunosuppressants, allopurinol or procainamide are used, or a combination of these risk factors, especially in patients with impaired renal function. Some patients had severe infections, in some cases, resistant to intensive antibiotic therapy. When appointing the drug Equator®, it is recommended that such patients periodically check the amount of white blood cells in the blood plasma. Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

Mitral stenosis / aortic stenosis / hypertrophic cardiomyopathy ACE inhibitors should be administered with caution to patients with mitral stenosis, as well as to patients with obstruction of the left ventricular outflow tract (aortic stenosis,hypertrophic cardiomyopathy).

Liver failure

Very rarely, when taking ACE inhibitors, cholestatic jaundice occurs. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. When jaundice or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors should cancel the drug Equator ® and carefully observe the patient.

Ethnic differences

In patients of the Negroid race, angioneurotic edema develops more often than in representatives of other races against the background of the administration of ACE inhibitors. ACE inhibitors may have a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race are more likely to have low renin activity.

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

Data on the impact on the ability to manage vehicles and mechanisms are not available. Because of the possibility of excessive reduction in blood pressure, development of dizziness,drowsiness and other side effects at the beginning of treatment, patients should refrain from driving a car and controlling other vehicles, work with machinery and perform other work requiring concentration.

Form release / dosage:

Tablets, 10 mg + 10 mg.

Packaging:

10 or 14 tablets in a blister of PVC / PE / PVDC - aluminum foil. For 1, 3 and 6 blisters (10 tablets) or 1, 2 and 4 blisters (14 tablets) in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep in original packaging to protect from light and moisture. Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-004629

Date of registration:15.01.2018

Expiration Date:15.01.2023

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

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp20.02.2018

Illustrated instructions

Instructions

Equator® (Ekvator®)