Expiration date: 02/2025

Composition and form of issue

Avacard pills 

1 tablet contains amlodipine 5 mg, lisinopril 5 or 10 mg

in a package of 10, 30 and 100 PCs.

Pharmacological action:

Aquagard - combination drug containing active substances: lisinopril and amlodipine.

Lisinopril

Inhibitor of angiotensin converting enzyme (ACE), reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to direct reduction in the excretion of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. It reduces the total peripheral vascular resistance (OPSS), blood PRESSURE, preload, pressure in the pulmonary capillaries, causing an increase in minute blood volume and increased myocardial tolerance to stress in patients with chronic heart failure. It expands the artery to a greater extent than veins. Some effects are explained by the effect on the renin-angiotensin-aldosterone system (rals). Long-term use reduces myocardial hypertrophy and resistive artery walls. Improves blood supply to ischemic myocardium.

ACE inhibitors extend the life expectancy of patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who have suffered acute myocardial infarction without clinical manifestations of heart failure.

The beginning of the drug in 1 h, the maximum antihypertensive effect is achieved after 6-7 h and maintained for 24 h. the duration of the effect also depends on the magnitude of the dose. With hypertension, the effect is noted in the first days after the start of treatment, stable action develops after 1-2 months of therapy. With the sharp abolition of lisinopril, there was no marked increase in blood PRESSURE. Lisinopril reduces albuminuria. It does not affect the concentration of glucose in the blood of patients with diabetes and does not lead to an increase in cases of hypoglycemia.

Amlodipine

Blocker of "slow" calcium channels, a derivative of dihydropyridine blocker of "slow" calcium channels (bmcc), has antianginal and antihypertensive effect, blocks calcium channels, reduces the face-membrane transition of calcium ions into the cell (to a greater extent in smooth muscle cells of blood vessels than in cardiomyocytes).

Antianginal effect is due to the expansion of the coronary and peripheral arteries and arterioles: with angina reduces the severity of myocardial ischemia, expanding peripheral arterioles, reduces OPSS, reduces postnagruzku heart, reduces myocardial oxygen demand. Expanding the coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina), prevents spasm of the coronary arteries (incl.Smoking). In patients with stable angina, a single daily dose increases exercise tolerance, increases the time before the onset of angina attack and "ischemic" depression of the ST segment, reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long dose-dependent antihypertensive effect. The antihypertensive effect is due to the direct vasodilating effect on the smooth muscles of the vessels. In hypertension, a single dose provides a clinically significant decrease in blood PRESSURE for 24 hours (in the patient's "lying" and "standing"). Orthostatic hypotension in the appointment of amlodipine is quite rare. Does not cause a decrease in the left ventricular ejection fraction. Reduces the degree of left ventricular hypertrophy. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect.

In diabetic nephropathy does not increase the severity of microalbumiuria. It does not have any adverse effect on metabolism and plasma lipid concentrations and can be used in the treatment of patients with asthma, diabetes and gout. A significant decrease in blood PRESSURE is observed after 6-10 h, the duration of the effect is 24 h. 

Indications

Essential hypertension (in patients, which shows the combined therapy).

Contraindications

• hypersensitivity to any of the drug components or to other dihydropyridine derivatives, other ACE inhibitors,
  
• angioedema in history, including caused by the use of other ACE inhibitors,
  
• hereditary and / or idiopathic angioedema,
  
• hemodynamically significant aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy,
  
• severe hypotension (systolic blood PRESSURE less than 90 mm Hg.V.),
  
• cardiogenic shock,
  
• pregnancy, lactation,
  
• the age of 18,
  
• acute myocardial infarction (during the first 28 days), unstable angina (except prinzmetals angina),
  
• lactose intolerance, lactose deficiency and glucose-galactose malabsorption.
  

Use during pregnancy and breast-feeding

The use of the drug Aquagard not recommended during pregnancy.

When the diagnosis of pregnancy the drug Avacard need to stop as early as possible.

Receiving 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 bones of the skull, intrauterine death). Data on the negative effects of the drug on the fetus in the case of use during the first trimester no. For newborns and infants who have been subjected to intrauterine exposure to ACE inhibitors, it is recommended to conduct careful monitoring for the timely detection of a marked decrease in blood PRESSURE, oliguria, hyperkalemia.

The safety of amlodipine during pregnancy has not been established, so the use during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

Lisinopril penetrates the placenta. There is no data on the penetration of lisinopril into breast milk.

There is no evidence of the release of amlodipine in breast milk.

However, it is known that other bmcc - dihydropyridine derivatives are excreted in breast milk.

The use of the drug Aquatard in the period of breast-feeding is not recommended.

If the use of the drug is necessary during lactation, breastfeeding should be stopped.

Dosage and administration

Tablet drug Aquagard taken orally once a day regardless of meal times, drinking plenty of fluids.

Adults

The recommended dose is 1 tablet of the drug Aquagard 1 times/day. At the beginning of therapy with the drug Equacard, symptomatic hypotension may develop, which more often occurs in patients with impaired water-electrolyte balance due to previous diuretic therapy. Priam diuretics should be discontinued 2-3 days before beginning therapy with drug Aquagard.

In cases where cancellation is impossible diuretics, the initial dose Aquagard is 1/2 tablet (5 mg+5 mg) 1 times/day., after taking which, for a few hours should provide monitoring of the patient because of the possible development of symptomatic hypotension.

Side effect

The frequency of adverse reactions listed below was determined according to the following (world health organization classification): very often - not less than 10%, often - not less than 1%, but less than 10%, infrequently - not less than 0.1%, but less than 1%, rarely - not less than 0.01%, but less than 0.1%, very rarely - less than 0.01%, including individual messages.

Lisinopril

On the part of the cardiovascular system: often-a marked decrease in blood PRESSURE, orthostatic hypotension, infrequent acute myocardial infarction, tachycardia, palpitations, Raynaud's syndrome, rarely - bradycardia, tachycardia, worsening of symptoms of chronic heart failure, violation of atrioventricular conduction, chest pain.

From the Central nervous system: often-dizziness, headache, infrequent-lability of mood, paresthesia, sleep disorders, stroke, rarely - confusion, asthenic syndrome, convulsive twitching of the muscles of the limbs and lips, drowsiness.

From the hematopoietic system and lymphatic system:rarely - reduction of hemoglobin, hematocrit, very rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, erythropenia, hemolytic anemia, lymphadenopathy, autoimmune diseases.

From the respiratory system: often-cough, infrequent-rhinitis, very rarely-sinusitis, bronchospasm, allergic alveolitis / eosinophilic pneumonia, shortness of breath.

From the digestive system: often-diarrhea, vomiting, infrequently - dyspepsia, changes in taste, abdominal pain, rarely - dryness of the oral mucosa, very rarely - pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis, liver failure, interstitial edema, anorexia.

On the part of the skin: infrequent-itching, rash, rarely-angioedema of the face, limbs, lips, tongue, larynx, urticaria, alopecia, psoriasis, very rarely-increased sweating, vasculitis, pemphigus, photosensitization, toxic epidermal necrolysis (Lyle's syndrome), erythema multiforme, Stevens-Johnson syndrome.

From the urinary system: often-a violation of kidney function, infrequently-uremia, acute renal failure, very rarely-anuria, oliguria, proteinuria.

From the reproductive system: infrequently-impotence, rarely-gynecomastia.

From the metabolism: very rarely - hypoglycemia.

From the laboratory indicators: infrequently - increasing the concentration of urea in the blood, hypercreatinemia, hyperkalemia, increased activity of "hepatic" transaminases, rarely - hyperbilirubinemia, hyponatremia, increased erythrocyte sedimentation rate, false positive test results for antinuclear antibodies.

From the musculoskeletal system: rarely-arthralgia / arthritis, myalgia.

Amlodipine

From the Central nervous system: often-headache (especially at the beginning of treatment), dizziness, increased fatigue, snotty, infrequent-General malaise, hypesthesia, asthenia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, increased excitability, depression, anxiety, increased sweating, rarely-convulsions, apathy, agitation, very rarely-ataxia, amnesia, amnesia Oh?

From the digestive system: often-nausea, abdominal pain, infrequent - vomiting, changes in the mode of defecation (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry mouth, thirst, rarely - hyperplasia of the gums, increased appetite, very rarely - pancreatitis, gastritis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of "liver" transaminases, hepatitis.

Of the cardiovascular system: often- peripheral edema (ankles and feet), palpitations, "tides" of blood to the skin, infrequently - excessive decrease in blood pressure, orthostatic hypotension, vasculitis, rarely - the development or worsening of chronic heart failure is very rare - fainting, shortness of breath, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, pulmonary edema, migraine.

From the hematopoietic and lymphatic systems: very rare - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the urinary system: infrequently-pollakiuria, painful urge to urinate, nicturia, very rarely-dysuria, polyuria.

On the part of the reproductive system and mammary glands: infrequently - gynecomastia, impotence.

From the respiratory system: infrequently - shortness of breath, rhinitis, very rarely-cough.

From the musculoskeletal system: infrequent muscle cramps, myalgia. arthralgia, back pain, arthrosis, rarely-myasthenia gravis.

From karnahorove: infrequently - alopecia: rare - dermatitis; very rarely-alopecia, xeroderma, cold clammy sweat, pigmentation disorders of the skin.

Allergic reactions: rarely-itching, rash (including erythematous, maculopapular rash), very rarely - urticaria, angioedema, erythema multiforme.

From the sensory organs: rare - tinnitus, blurred vision, diplopia, violation ccomodation, xerophthalmia, conjunctivitis, eye pain, rarely - parosmia.

From the metabolism: very rarely - hyperglycemia.

Other: infrequently-weight loss, weight gain, taste perversion, nose bleeding, chills.

Special instruction

Drug treatment Aquagard can start only after the correction of hyponatremia and restoration of circulating blood volume.

After taking the first dose of the drug is recommended careful control of blood PRESSURE, perhaps a significant decrease in blood PRESSURE with the development of symptomatic hypotension. Most often, a marked decrease in blood PRESSURE occurs with a decrease in BCC caused by diuretic therapy, a decrease in salt content in food, dialysis, diarrhea or vomiting.

In hypotension, the patient is given a horizontal position and, if necessary, a solution is injected to fill the volume of circulating fluid (infusion of 0.9% sodium chloride solution).

Such rules should be followed when using the drug Equacard in patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood PRESSURE can lead to myocardial infarction or stroke.

In case of aortic stenosis, hypertrophic obstructive cardiomyopathy, the appointment of a vasodilator requires caution.

During the period of drug therapy Aquagard® it is necessary to control body weight and salt intake, shows the assignment of a proper diet.

It is necessary to maintain oral hygiene and supervision at the dentist (to prevent pain, bleeding and hyperplasia of the gums).

During the period of therapy, periodic monitoring of peripheral blood is necessary, since it is impossible to exclude the potential risk of agranulocytosis, periodic monitoring of peripheral blood is required.

In violation of renal function, for example, with renal artery stenosis (especially bilateral or with stenosis of the arteries of the single kidney), hyponatremia, dehydration, circulatory failure, drug administration can provoke deterioration of renal function and acute renal failure, reversible after treatment. Control of patients with impaired renal function is necessary.

In elderly patients may increase T1 / 2 amlodipine and decrease clearance of the drug. More careful monitoring of patients in this category is needed.

In violation of liver function half-life of amlodipine increases, such patients are prescribed the drug with caution, after evaluating the benefits and risks. When using ACE inhibitors may develop angioedema of the face, limbs, lips, tongue, epiglottis or larynx, requiring immediate cessation of treatment with the drug and the establishment of medical supervision to complete regression of symptoms. Angioedema with laryngeal edema can be fatal. Edema of the tongue, epiglottis or larynx can cause airway obstruction, so it is necessary to immediately carry out appropriate therapy (0.3-0.5 ml 1:1000 solution of epinephrine (adrenaline) p/C) and/or PI measures to ensure airway patency. In cases where swelling is localized only on the face and lips, the condition often goes without treatment, but it is possible to use antihistamines.

The risk of angioedema increases in patients who have a history of angioedema from the use of ACE inhibitors.

Patients, taking ACE inhibitors during the procedure of desensitization on the venom of the Hymenoptera, rarely, can develop life-threatening anaphylactoid reactions. This can be avoided if the treatment with an ACE inhibitor is temporarily discontinued before each procedure of desensitization with PA hymenopter.

Surgical intervention / General anesthesia: in the application of funds for General anesthesia with antihypertensive effect and during extensive surgical procedures lisinopril inhibits the formation of angiotensin-II in response to the compensatory renin. With such arterial hypotension, blood PRESSURE is normalized by increasing the volume of circulating blood.

Before surgery (including dental surgery), the surgeon/anesthesiologist should be informed about the use of an ACE inhibitor.

Anaphylactoid reactions are also observed in patients on hemodialysis using high-flow dialysis membranes (AN69), which simultaneously take ACE inhibitors. In such cases, it is necessary to consider the possibility of using another type of membrane for dialysis or other antihypertensive agent. When choosing a dose should be taken into account that in elderly patients, both active substances are determined in the blood at a higher concentration, while the effectiveness does not change.

With the use of ACE inhibitors was noted to cough. Cough dry, long, which disappears after stopping treatment with ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of an ACE inhibitor.

Drug interaction

Lisinopril

With caution, lisinopril should be used simultaneously with potassium - spiking diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations, salt substitutes containing potassium, cyclosporine-the risk of hyperkalemia increases, especially with impaired renal function. Therefore, these combinations should be used only on the basis of an individual decision of the doctor with regular monitoring of serum potassium and kidney function.

With simultaneous use with diuretics and other antihypertensive agents, the antihypertensive effect of lisinopril increases.

While the use of non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2)), estrogen, and sympathomimetics, reduced antihypertensive effect of lisinopril. NSAIDs, including COG-2, and ACE inhibitors increase serum potassium and may impair kidney function. This effect is usually reversible.

Lisinopril slows down the excretion of lithium, so while the use of a reversible increase in its concentration in the blood plasma, which can increase the likelihood of adverse events, so you should regularly monitor the concentration of lithium in the blood serum.

While the use of antacids and wheels tirami nom decreases the absorption of lisinopril from GK G.

Ethanol increases the effect of lisinopril.

While the use of insulin and hypoglycemic agents for oral administration increases the risk of hypoglycemia.

With simultaneous use of lisinopril with vasodilators, barbiturates, antipsychotics (neuroleptics), tricyclic antidepressants.

Bmkk, beta-blockers may increase the antihypertensive effect. While the use of ACE inhibitors and gold preparations (sodium aurothiomalate) described a syndrome that includes flushing, nausea, vomiting and decrease in blood pressure.

Combined use with allopurinol, procainamide, cytostatics can lead to leukopenia.

Amlodipine

Amlodipine can be safely used for the treatment of hypertension with thiazide diuretics, alpha-blockers or ACE inhibitors.

Unlike other bmcc clinically significant interaction of amlodipine was not detected in combination with NSAIDs, including indomethacin.

It is possible to increase the antianginal and hypotensive action of bmcc in combination with thiazide and" loop " diuretics, ACE inhibitors and nitrates, as well as strengthening their antihypertensive action while using with alpha1-adrenoblokatorami.

Erythromycin when combined increases Cmax amlodipine in young patients by 22%, and in elderly patients-by 50%.

Beta-blockers while using amlodipine can be caused by an exacerbation of the course of chronic heart failure.

Although in the study of amlodipine negative inotropic action is not usually observed, however, some bmcc may increase the severity of negative inotropic effects of antiarrhythmic agents, causing prolongation of THE Qt interval (eg, amiodarone and quinidine).

A single dose of 100 mg of sildenafil in patients with hypertension has no effect on the parameters of the pharmacokinetics of amlodipine.

Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Ethanol (drinks containing alcohol): amlodipine at a single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiretroviral drugs (ritonavir) increase plasma concentrations of bmcc, including amlodipine.

Neuroleptics and isoflurane enhancement of hypotensive action of dihydropyridine derivatives.

Calcium supplementation may reduce the effect of bmcc.

When combined with the use of amlodipine lithium drugs may increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, noise and ears).

Amlodipine does not change the pharmacokinetics of cyclosporine.

It does not affect the concentration of serum digoxin and its renal clearance.

Does not have a significant effect on the effect of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In in vitro studies, amlodipine does not affect plasma protein binding, digoxin, phenytoin, warfarin, and indomethacin.

Grapefruit juice: simultaneous single administration of 240 mg of grapefruit juice and 10 mg of amlodipine inside is not accompanied by a significant change in the pharmacokinetics of amlodipine.

Aluminum-or magnesium-containing antacids: their single administration does not have a significant effect on the pharmacokinetics of amlodipine.

Overdose

Lisinopril

Symptoms: marked decrease in blood PRESSURE, dryness of the mucous membrane of the oral cavity, violation of water-electrolyte balance, renal insufficiency, increased breathing, tachycardia, palpitations, bradycardia, dizziness, anxiety, increased irritability, cough, drowsiness, urinary retention, constipation. 

Treatment: there is no specific antidote. Gastric lavage, the use of enterosorbents and laxatives. It is shown in / in the introduction of 0.9% sodium chloride solution. In the case of resistant to the treatment of bradycardia, it is necessary to use an artificial pacemaker. It is necessary to control the blood PRESSURE, water-electrolyte balance. Hemodialysis is effective.

Amlodipine

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

Treatment: gastric lavage, the use of activated carbon (especially in the first 2 hours after overdose), maintenance of the cardiovascular system, elevated position of the lower extremities, monitoring of the heart and lungs, control of the volume of circulating blood (BCC) and diuresis. For restoration

vascular tone the use of vasoconstrictors (in the absence of contraindications to their use), to eliminate the effects of blockade of calcium channels in/in the introduction of calcium gluconate. Hemodialysis is not effective.

Storage conditions

The drug should be stored out of reach of children, in a dark place at a temperature not exceeding 25°C.

Shelf life-3 years.