Equator

Active material: Amlodipine, Lisinopril
When ATH: C09BB
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.04
Manufacturer: GEDEON RICHTER Ltd. (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills round, flat, white or nearly white, chamfered, with Valium on one party and chasing “A L” on the other side.

Excipients: magnesium stearate, sodium carboxymethyl starch type A, microcrystalline cellulose.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Combined antihypertensive drug, soderzhashtiy lisinopril and amlodipine.

Lisinopril – ACE inhibitor, reduces blood levels of angiotensin II and aldosterone, while increasing levels of bradykinin – sosudorasshiryayushtego mediator. It affects the tissue renin-angiotensin system. It lowers blood pressure and systemic vascular resistance, before- and afterload, the pressure in the pulmonary capillaries, no effect on heart rate, thus possible to increase the cardiac output and increased blood flow in the kidney. It expands the artery to a greater extent, than veins. It improves blood flow to ischemic myocardium. Prolonged use reduces myocardial hypertrophy and arterial wall resistance. It increases tolerance to physical stress infarction in patients with chronic heart failure. Playing a role in the restoration of endothelial function, damaged as a result of hyperglycemia.

It increases life expectancy of patients with chronic heart failure. Slows the progression of left ventricular dysfunction after myocardial infarction, uncomplicated heart failure.

The hypotensive effect observed after 1 hours after oral administration, peaking through 6 no. Duration of action is dose-dependent and is 24 no. Prolonged treatment effectiveness is not reduced. In a dramatic withdrawal of treatment with a sharp increase in blood pressure does not occur.

Although the primary effect, proyavlyayushtiysya in vozdeystvii renin-angiotensin-alydosteronovuyu sistemu, effective and hypertension with low renin.

Lisinopril lowers albuminuria is not only due to the reduction of blood pressure, but also due to changes in glomerular hemodynamics and tissue structure. No effect on blood sugar levels in diabetic patients, and does not increase the incidence of hypoglycemia.

Amlodipine – Calcium channel blockers slow III generation, It has antianginal and hypotensive action. Prevents entry of calcium into the cells of the myocardium and, more, smooth muscle cells in the vascular wall. Reduces the tone of smooth muscles of arterioles, PR and, Consequently, FROM.

It has antianginal effects by expanding arteries and arterioles and afterload reduction. It reduces the need for oxygen and energy consumption of the myocardium, tk. It does not cause reflex tachycardia. Probably, due to the expansion of the coronary arteries and arterioles increases oxygen supply to the intact (especially in vasospastic angina) and ischemic areas of the myocardium. When angina improves exercise tolerance, prevents the development of angina attack and the formation of ischemic ST interval, reducing the frequency of angina attacks and need for nitroglycerin. It does not affect the conduction and myocardial contractility.

It has long, dose-dependent hypotensive effect. Do not reduce the left ventricular ejection fraction. Reduces left ventricular hypertrophy. It has anti-atherosclerotic and cardioprotective effect in ischemic heart disease. Application for digoxin therapy, diuretics and ACE inhibitors does not increase the risk of death in patients with chronic heart failure (III-IV FC according to the NYHA classification).

Medlennaya absorption, broad distribution in the body and slow elimination provides sustained action, allowing to take the drug 1 time / day. More, than 24 h provides significant from a clinical point of view, reduction in blood pressure in the sitting position and lying down. Action develops gradually, through 2-4 hours after administration and not accompanied by arterial hypotension.

It inhibits platelet aggregation, increases glomerular filtration, It has a weak natriuretic effect, diabetic nephropathy does not increase microalbuminuria.

It has no negative impact on the metabolic processes, It does not change the level of plasma lipids. You can assign patients with concomitant asthma, diabetes and gout.

The combination of lisinopril amlodipine in a medicinal product can prevent the development of possible adverse effects, protivoregulyatsiey caused any of the active substances. So, Calcium channel blockers slow, directly expanding arterioles, can lead to sodium retention and body fluids and, Consequently, can activate the renin-angiotensin-aldosterone system. ACE inhibitor blocks this process, normalizes the response to salt loading.

Pharmacokinetics

Lisinopril

Absorption

After ingestion unaltered enters the systemic circulation and in 6 h reaches C_max plasma (90 ng / ml). Absorption sostavlyaet 30% (6-60%), bioavailability 29%.

Distribution

Associated exclusively with ACE.

Penetrates the GEB and placental barrier.

Metabolism

Do not metabolized.

Deduction

Excreted in the urine as unchanged, T_1/2 12.6 no. After removing most of the free fraction of lisinopril displayed, associated with ACE, providing lasting therapeutic effect.

Pharmacokinetics in special clinical situations

In renal insufficiency the excretion of lisinopril slows. Displayed with dialysis.

Amlodipine

Absorption

After oral administration of amlodipine is slowly and almost completely (90%) absorbed from the gastrointestinal tract. C_max plasma levels achieved after 6-10 no. Treated effect “first pass” through the liver. Bioavailability 64-80%.

Distribution

The equilibrium state is achieved on 7-8 day regular admission. V_d about 20 l / kg.

The binding to plasma proteins – 95-98%. It penetrates through the BBB.

Metabolism

Subjected to intensive metabolism in the liver (90%). Most converted in the liver into inactive metabolite.

Deduction

10% amlodipine is excreted in the urine in unchanged form, 60% – as metabolites; 20-25% – in the form of metabolites with bile through the intestines; It passes into breast milk. Total clearance 500 ml / min.

Excretion is biphasic. T_1/2 the final phase 35-50 time.

Pharmacokinetics in special clinical situations

T_1/2 with hypertension – 48 no, in elderly patients – to 65 no, hepatic failure – to 60 no, T_1/2 and increases in severe heart failure, It does not affect the degree of renal impairment. Around the same time achieved C_max plasma in young and elderly patients. In elderly patients, the clearance of amlodipine is slightly lower, T_1/2 AUC and longer. Do not dialyzed. Portability is the same, therefore, dose adjustment in elderly patients is not required.

Equator^®

The interaction between the active ingredients, members of the drug, unlikely. AUC, and the amount of time to reach C_max plasma, T_1/2 It does not change compared with each individual active substance. Eating does not affect the absorption of active substances. Prolonged circulation in the body of both active substances allows the drug 1 time / day.

Testimony

- Essential hypertension (When the need for combination therapy).

Dosage regimen

Recommended for use in cases, when taking medication, containing the individual active substances of the Equator^® at the same doses, It does not provide the necessary control of blood pressure.

Patient, not receiving antihypertensives daily dose – 1 tab. regardless of the meal.

In the case of previous therapy with diuretics for 2-3 days before the start of the reception of the Equator^® diuretic should be discontinued. If you can not cancel a diuretic, the initial dose of the Equator^® is 1/2 tab. / day. After taking the drug the patient is required to provide medical supervision for several hours because of the possible development of symptomatic hypotension.

At Heart Failure and severe hypertension maintenance dose is 1 tab.

At renal insufficiency and QC 30-70 ml / min appoint half the usual starting dose (tk. elimination of lisinopril is carried out by the kidneys). The maintenance dose depends on the individual patient's response, during therapy requires regular monitoring of renal function, Sodium and potassium levels in the blood.

At liver diseases elimination of amlodipine may be delayed, therefore, the initial dose of the Equator^® is 1/2 tab. per day. Use of the drug in these patients requires special care.

Side effect

Cardio-vascular system: 1-3% – orthostatic hypotension; rarely – Arrhythmia, palpitations, tachycardia (probably, due to excessive reduction of blood pressure in patients at high risk of myocardial infarction, cerebrovascular stroke).

From the central and peripheral nervous system: 8% – headache, 3% – dizziness; 1-3% – weakness; rarely – hypersomnia, muscular fasciculation of limbs and lips, asthenia, mood lability, confusion.

The respiratory system: 5% – dry cough.

From the digestive system: possible 1-3% – diarrhea, nausea, vomiting; 1% – increase in liver enzymes and bilirubin in the blood (especially for kidney, diabetes and hypertension, renovascular); rarely – bowel dysfunction, dry mouth, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis, giperplaziya right, decreased appetite.

From the urinary system: increased creatinine, BUN (especially for kidney, diabetes and hypertension, renovascular); rarely – impairment of renal function, frequent urination, oligurija, anurija, acute renal failure, uremia, proteinuria.

Metabolism: hyperkalemia.

Dermatological reactions: 1-3% – itching, skin rash, redness of the skin; rarely – increased perspiration, alopecia.

Allergic reactions: rarely – hives; 0.1% – angioneurotic edema of the face, limbs, lips, language, epiglottis, larynx. In such cases, stop treatment and monitor the patient until the complete disappearance of all symptoms.

From the hematopoietic system: leukopenia, neutropenia, agranulocytosis (the effect of an ACE inhibitor), thrombocytopenia, erythropenia, long term treatment may be a slight decrease in hemoglobin concentration and hematocrit.

Other: 1-3% – swelling of the ankles legs, chest pain, arthralgia; rarely – syndrome, accompanied by the appearance of antinuclear antibodies, acceleration of ESR and arthralgia, impotence.

Adverse reactions are usually poorly defined, and the transient nature, cancellation of the treatment required in rare cases. Side effects, caused by a combination drug, there are no more, than in the case of reception of each component separately.

Contraindications

- Hereditary or idiopathic hemodynamically significant stenosis of the aortic or mitral valve;

- Gipertroficheskaya cardiomyopathy;

- Severe hypotension;

- Cardiogenic shock;

- A history of angioedema, incl. caused by the use of other ACE inhibitors;

- Pregnancy;

- Lactation;

- Childhood and adolescence up 18 years (due to lack of data on efficacy and safety in this age group);

- Hypersensitivity to the drug or to other dihydropyridine derivatives.

FROM caution use in patients with cerebrovascular diseases (incl. when cerebrovascular insufficiency), CHD, coronary insufficiency, bradycardia, tachycardia, chronic heart failure, decompensated, with mild to moderate hypotension, acute myocardial infarction and one month after the, severe autoimmune diseases (incl. scleroderma, SLE), the oppression of bone marrow hematopoiesis, diabetes, hyperkalemia, condition after kidney transplantation, renal failure, a diet with restriction of sodium, in elderly patients, hepatic failure.

Pregnancy and lactation

The drug is contraindicated during pregnancy.

In identifying pregnancy treatment should be discontinued as soon as possible.

Acceptance of lisinopril in II and III trimester of pregnancy may cause fetal death and injury as a result of its impact on the kidneys (hypotension, renal failure, hyperkalemia). Reducing the amount of amniotic fluid may cause deformation of the skull and face, disruption of limb development, pulmonary hypoplasia and fetal death. Information about these and other actions in the earlier stages of pregnancy are absent.

The drug is contraindicated during lactation because of the isolation of amlodipine in breast milk. Data, indicating penetration of lisinopril in breast milk, no.

Cautions

Treatment can begin only after the correction of hyponatremia and recovery in the event of dehydration bcc.

After the first dose of the drug should be carefully monitored for changes in blood pressure. Perhaps a significant reduction in blood pressure to the development of symptomatic hypotension in patients, receiving diuretics and in a state of dehydration and / or hyponatremia resulting hyperhidrosis, prolonged vomiting or diarrhea. If hypotension give the patient a horizontal position and if necessary I / O solution is introduced, vospolnyayushtiy OCK (infusion of saline).

In heart failure, decompensated, CHD, cerebrovascular diseases Equator^® can cause hypotension, myocardial infarction or stroke.

When aortic stenosis, hypertrophic cardiomyopathy appointment vasodilator requires caution.

During treatment requires monitoring of body weight and seeing your dentist.

You should regularly monitor the pattern of peripheral blood for early detection of possible agranulocytosis.

If the kidney function, eg, Renal artery stenosis (especially, bilateral or stenosis of the artery only kidney), giponatriemii, Dehydration, circulatory failure, the drug can cause deterioration in kidney function and acute renal failure, reversible after cessation of treatment.

With the defeat of liver T_1/2 amlodipine increases, such patients the drug is prescribed with caution, after evaluating the ratio of benefits and risks.

Perhaps the development of reaction to an ACE inhibitor in the form of facial angioedema, limbs, lips, language, epiglottis or larynx, demands the immediate cessation of drug treatment and the establishment of medical supervision of the patient until the complete disappearance of all symptoms.

Angioedema, lokalizovannыy person, lips, limbs, usually, spontaneously disappears, receiving antihistamines, It helps to reduce the symptoms.

Angioedema of the larynx may be fatal. Swelling of the tongue, epiglottis and larynx can cause airway obstruction and requires immediate medical intervention: introduction 0.1% epinephrine (adrenaline) n / a (0.3-0.5 ml, ie. 0.3-0.5 mg) or slowly / in (0.1 ml, ie. 0.1 mg), the use of GCS, antihistaminics and monitoring vital body functions.

Surgery / general anesthesia: the application of funds for general anesthesia with the hypotensive effect, and during major surgery Lisinopril inhibits the formation of angiotensin II, in response to compensatory renin release. With such hypotension normalize blood pressure by increasing bcc.

Use of polyacrylic membrane for dialysis during treatment with an ACE inhibitor can cause anaphylactic shock, to avoid their simultaneous use, or to use a different type of dialysis membrane, or other antihypertensive agents.

Desensitization against arthropods during treatment with ACE inhibitors can cause an anaphylactic reaction. The reactions can be avoided, previously temporarily interrupting treatment with an ACE inhibitor.

In the selection of dose should be considered, that elderly patients are both active substances are defined in greater concentration in the blood, the efficiency is not changed.

Effects on ability to drive vehicles and management mechanisms

The drug can affect the ability to drive the vehicle and operate machinery, especially at the beginning of treatment, when the risk of hypotension is more likely. The dose and dosing regimen, where you can drive a car and perform the work, associated with an increased risk of injury, set individually.

Overdose

Symptoms: vasodilation with marked decrease in blood pressure and reflex tachycardia appearance.

Treatment: simptomaticheskaya therapy, Control of cardiac activity, FROM, diuresis and fluid and electrolyte balance, if necessary its correction. In marked decrease in blood pressure, give the patient supine position, Raise the lower limbs; when poor therapeutic response to / in the introduction of the substituents the liquid may require the introduction of dopamine. For termination of amlodipine can be entered into / from calcium gluconate. Because of the slow absorption of amlodipine in some cases washed stomach, activated carbon. Lisinopril is output via hemodialysis; strong degree of protein binding of blood dialysis does amlodipine ineffective.

Drug Interactions

Microsomal oxidation inhibitors can increase the concentration of amlodipine in plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes decrease.

While the use of potassium-sparing diuretics (spironolactone, triamterene, amilorid), potassium supplements, salt substitutes and food supplements, containing potassium, may develop hyperkalemia, especially in patients with impaired renal function. When using such combinations requires special care. Appointment possible after careful evaluation of the benefits and risks of therapy, subject to regular control of the content of potassium in the blood and kidney function.

With the simultaneous use of the drug with diuretic possible sharp decline in blood pressure, other antihypertensives (beta-blockers, calcium channel blockers (including verapamil), ACE inhibitors, nitratami) there is an additive effect (in combination therapy requires caution).

May decrease the effectiveness of the drug, while the use of NSAIDs (particularly with indomethacin, tk. NSAIDs cause sodium retention and block the synthesis of prostaglandins in the kidneys), Estrogen, adrenostimulâtorami, simpatomimetikami (in combination therapy requires caution).

In an application with lithium may deteriorate excretion of lithium, necessary to monitor the level of lithium in the blood plasma (in combination therapy requires caution).

Antacids and cholestyramine reduce the absorption of active substances of the drug from the gastrointestinal tract (in combination therapy requires caution).

Amiodarone, quinidine, beta-blockers, antipsychotics (neuroleptics) may increase the hypotensive effect.

Calcium can reduce the effect of calcium channel blockers.

Prokaynamyd, quinidine and other drugs, prolonging the QT interval, can contribute to a significant increase in its.

It has no effect on the pharmacokinetics of digoxin and warfarin. Cimetidine have no influence on amlodipine farmakokinetiku.

Lisinopril reduces the loss of potassium in the treatment of thiazide diuretics.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 15 ° to 25 ° C. Shelf life – 3 year.