Ekvacard (Tablets) Instructions for Use

Marketing Authorization Holder

Micro Labs Limited (India)

ATC Code

C09BB03 (Lisinopril and Amlodipine)

Active Substances

Lisinopril (Rec.INN registered by WHO)

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Ekvacard	Tablets 5 mg+5 mg: 10, 20, 30 or 100 pcs.
		Tablets 5 mg+10 mg: 10, 20, 30 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets pink in color, round, flat-cylindrical, with a bevel, with a score on one side.

Excipients: lactose 106.34 mg, corn starch 58.86 mg, povidone 5.7 mg, talc 3.8 mg, magnesium stearate 1.95 mg, Ponceau 4R dye 0.1 mg.

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

Tablets white in color, round, flat-cylindrical, with a bevel, with a score on one side.

Excipients: lactose 100.625 mg, corn starch 58.66 mg, povidone 5.7 mg, talc 3.8 mg, magnesium stearate 2 mg.

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

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Combined antihypertensive agent (CCB + ACE inhibitor)

Pharmacological Action

A combined drug containing active substances: Lisinopril and Amlodipine.

Lisinopril

An angiotensin-converting enzyme (ACE) inhibitor, it reduces the formation of angiotensin II from angiotensin I. The decrease in angiotensin II content leads to a direct reduction in aldosterone secretion. It reduces the degradation of bradykinin and increases the synthesis of prostaglandins. It reduces total peripheral vascular resistance (TPR), blood pressure, preload, pulmonary capillary pressure, causes an increase in cardiac output and an increase in myocardial tolerance to stress in patients with chronic heart failure. It dilates arteries to a greater extent than veins. Some effects are explained by the impact on the renin-angiotensin-aldosterone system (RAAS). With long-term use, it reduces hypertrophy of the myocardium and walls of resistive-type arteries. It improves blood supply to the ischemic myocardium.

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

The onset of the drug’s action is within 1 hour, the maximum antihypertensive effect is achieved in 6-7 hours and persists for 24 hours. The duration of the effect also depends on the dose taken. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months of therapy. A sharp increase in blood pressure was not observed upon abrupt withdrawal of lisinopril. Lisinopril reduces albuminuria. It does not affect blood glucose concentration in patients with diabetes mellitus and does not lead to an increased incidence of hypoglycemia.

Amlodipine

A slow calcium channel blocker, a dihydropyridine derivative, a slow calcium channel blocker (CCB), it has antianginal and antihypertensive action, blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).

The antianginal action is due to the dilation of coronary and peripheral arteries and arterioles: in angina, it reduces the severity of myocardial ischemia; by dilating peripheral arterioles, it reduces TPR, decreases cardiac afterload, and reduces myocardial oxygen demand. By dilating coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases oxygen supply to the myocardium (especially in vasospastic angina); prevents spasm of coronary arteries (including that caused by smoking). In patients with stable angina, a single daily dose increases exercise tolerance, increases the time to onset of angina attack and “ischemic” ST-segment depression, and reduces the frequency of angina attacks and consumption of nitroglycerin and other nitrates.

It has a long-term, dose-dependent antihypertensive effect. The antihypertensive action is due to a direct vasodilatory effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in both the “lying” and “standing” positions of the patient). Orthostatic hypotension is quite rare when amlodipine is prescribed. It does not cause a decrease in left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy. It does not affect myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, and has a weak natriuretic effect.

In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have any adverse effect on metabolism and plasma lipid concentrations and can be used in the therapy of patients with bronchial asthma, diabetes mellitus, and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

Ekvacard^®

The combination of lisinopril with amlodipine in one medicinal product helps prevent the development of possible undesirable effects caused by counter-regulation by any of the active substances. Thus, a slow calcium channel blocker, by directly dilating arterioles, can lead to sodium and fluid retention in the body, and consequently, can activate the RAAS. The ACE inhibitor blocks this process and normalizes responses to salt load.

Pharmacokinetics

Lisinopril

After oral administration, Lisinopril is absorbed from the gastrointestinal tract on average by 25%, but absorption can vary from 6 to 60%. Bioavailability is 29%. C_max in blood plasma is reached after 7 hours. Food intake does not affect the absorption of lisinopril. Lisinopril slightly binds to blood plasma proteins. Permeability through the blood-brain and placental barrier is low.

Lisinopril is not biotransformed in the body.

It is excreted by the kidneys unchanged. T_1/2 is 12.6 hours. The clearance of lisinopril is 50 ml/min. The decrease in serum concentration of lisinopril occurs in two phases.

In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced, bioavailability is 16%.

In patients with renal failure (creatinine clearance (CrCl) less than 30 ml/min), the concentration of lisinopril is several times higher than the concentrations in the blood plasma of healthy volunteers, and an increase in the time to reach C_max in blood plasma and an increase in T_1/2 are noted.

In elderly patients, C_max of the drug in blood plasma and AUC are 2 times greater than in young patients.

In patients with liver cirrhosis, the bioavailability of lisinopril is reduced by 30%, and clearance by 50% compared to patients with normal liver function.

In elderly patients, the concentration of lisinopril in the blood is increased by an average of 60%.

Amlodipine

After oral administration, Amlodipine is slowly absorbed from the gastrointestinal tract. The mean absolute bioavailability is 64%, C_max in serum is observed after 6-9 hours. Steady-state concentrations (C_ss) are reached after 7-8 days of therapy.

Food intake does not affect the absorption of amlodipine. The mean V_d is 21 L/kg of body weight, which indicates that most of the drug is in the tissues, and a smaller part is in the blood. Most of the amlodipine in the blood (95%) is bound to blood plasma proteins. Amlodipine undergoes slow but active metabolism in the liver in the absence of a significant first-pass effect. Metabolites do not have significant pharmacological activity. After a single oral dose, T_1/2 varies from 35 to 50 hours, with repeated use T_1/2 is approximately 45 hours. About 60% of the orally administered dose is excreted by the kidneys mainly as metabolites, 10% unchanged, and 20-25% through the intestine with bile. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 L/h/kg).

In elderly patients (over 65 years), the elimination of amlodipine is slowed (T_1/2 is 65 hours) compared to young patients, but this difference has no clinical significance. The prolongation of T_1/2 in patients with hepatic insufficiency suggests that with long-term use, accumulation of the drug in the body will be higher (T_1/2 up to 60 hours). Renal failure does not significantly affect the kinetics of amlodipine. In patients with impaired renal function, changes in amlodipine concentration in blood plasma do not correlate with the degree of renal failure. A slight increase in T_1/2 is possible.

Amlodipine penetrates the blood-brain barrier. It is not removed by hemodialysis.

Ekvacard^®

Pharmacokinetic interaction between the active substances included in the drug is unlikely. AUC, time to reach and values of C_max, T_1/2 do not change compared to the indicators of each individual active substance. Food intake does not affect the absorption of active substances. The long circulation in the body of both active substances makes it possible to take the drug once a day.

Indications

• Essential hypertension (for patients who are indicated for combination therapy).

ICD codes

Dosage Regimen

Ekvacard^® tablets are taken orally once a day, regardless of meal time, with a sufficient amount of liquid.

Adults

The recommended dose is 1 tablet of Ekvacard^® once a day. At the beginning of therapy with Ekvacard^®, symptomatic arterial hypotension may develop, which occurs more often in patients with water-electrolyte imbalance due to previous diuretic therapy. Diuretic intake should be discontinued 2-3 days before starting therapy with Ekvacard^®.

In cases where diuretic withdrawal is not possible, the initial dose of Ekvacard^® is 1/2 tablet (5 mg+5 mg) once a day, after which the patient should be observed for several hours due to the possible development of symptomatic arterial hypotension.

Renal impairment

In patients with impaired renal function, it is recommended to use Ekvacard^® at a dose of 5 mg+5 mg (due to increased T_1/2 of lisinopril). The maintenance dose is selected depending on the tolerance of the therapy; monitoring of renal function, plasma potassium and sodium levels is required.

Hepatic impairment

In patients with impaired liver function, it is recommended to use Ekvacard^® at a dose of 5 mg+5 mg (due to increased T_1/2 of amlodipine).

Adverse Reactions

The frequency of adverse reactions listed below was determined according to the following (World Health Organization classification): very common – not less than 10%; common – not less than 1%, but less than 10%; uncommon – not less than 0.1%, but less than 1%; rare – not less than 0.01%, but less than 0.1%; very rare – less than 0.01%, including individual reports.

Lisinopril

From the cardiovascular system common – pronounced decrease in blood pressure, orthostatic hypotension; uncommon – acute myocardial infarction, tachycardia, palpitation; Raynaud’s syndrome; rare – bradycardia, tachycardia, worsening of symptoms of chronic heart failure, impaired atrioventricular conduction, chest pain.

From the central nervous system common – dizziness, headache; uncommon – mood lability, paresthesia, sleep disorders, stroke; rare – confusion, asthenic syndrome, convulsive twitching of limb and lip muscles, drowsiness.

From the hematopoietic and lymphatic systems rare – decrease in hemoglobin, hematocrit; very rare – leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, erythrocytopenia, hemolytic anemia, lymphadenopathy, autoimmune diseases.

From the respiratory system common – cough; uncommon – rhinitis; very rare – sinusitis, bronchospasm, allergic alveolitis/eosinophilic pneumonia, dyspnea.

From the digestive system common – diarrhea, vomiting; uncommon – dyspepsia, taste disturbances, abdominal pain; rare – dry oral mucosa; very rare – pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis, liver failure, interstitial edema, anorexia.

From the skin uncommon – skin itching, rash; rare – angioedema of the face, extremities, lips, tongue, larynx, urticaria, alopecia, psoriasis; very rare – increased sweating, vasculitis, pemphigus, photosensitivity, toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, Stevens-Johnson syndrome.

From the urinary system common – impaired renal function; uncommon – uremia, acute renal failure; very rare – anuria, oliguria, proteinuria.

From the reproductive system uncommon – impotence, rare – gynecomastia.

From metabolism very rare – hypoglycemia.

From laboratory parameters uncommon – increased blood urea concentration, hypercreatininemia, hyperkalemia, increased activity of “liver” transaminases, rare – hyperbilirubinemia, hyponatremia, increased erythrocyte sedimentation rate, false-positive test results for antinuclear antibodies.

From the musculoskeletal system rare – arthralgia/arthritis, myalgia.

Amlodipine

From the central nervous system common – headache (especially at the beginning of treatment), dizziness, increased fatigue, drowsiness; uncommon – general malaise, hypesthesia, asthenia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, increased excitability, depression, anxiety, increased sweating; rare – convulsions, apathy, agitation; very rare – ataxia, amnesia.

From the digestive system common – nausea, abdominal pain; uncommon – vomiting, change in bowel habits (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry oral mucosa, thirst; rare – gingival hyperplasia, increased appetite; very rare – pancreatitis, gastritis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of “liver” transaminases, hepatitis.

From the cardiovascular system common – peripheral edema (ankles and feet), palpitation, “flushing” of blood to the skin of the face; uncommon – excessive decrease in blood pressure, orthostatic hypotension, vasculitis; rare – development or worsening of the course of chronic heart failure; very rare – syncope, dyspnea, heart rhythm disturbances (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 uncommon – pollakiuria, painful urge to urinate, nocturia; very rare – dysuria, polyuria.

From the reproductive system and mammary glands uncommon – gynecomastia, impotence.

From the respiratory system uncommon – dyspnea, rhinitis; very rare – cough.

From the musculoskeletal system uncommon – muscle cramps, myalgia, arthralgia, back pain, arthrosis; rare – myasthenia.

From the skin uncommon – alopecia: rare – dermatitis; very rare – alopecia, xeroderma, cold clammy sweat, skin pigmentation disorder.

Allergic reactions rare – skin itching, rash (including erythematous, maculopapular rash); very rare – urticaria, angioedema, erythema multiforme.

From the sensory organs uncommon – ringing in the ears, visual impairment, diplopia, accommodation disorder, xerophthalmia, conjunctivitis, eye pain; very rare – parosmia.

From metabolism very rare – hyperglycemia.

Other uncommon – weight loss, weight gain, taste perversion, nosebleed, chills.

Contraindications

• Hypersensitivity to any component of the drug or to other dihydropyridine derivatives, other ACE inhibitors;
• History of angioedema, including that caused by the use of other ACE inhibitors;
• Hereditary and/or idiopathic angioedema;
• Hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy;
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
• Cardiogenic shock;
• Pregnancy, lactation period;
• Age under 18 years;
• Acute myocardial infarction (within the first 28 days), unstable angina (except for Prinzmetal’s angina);
• Lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

With caution: cerebrovascular diseases (including cerebral circulation insufficiency), coronary artery disease, coronary insufficiency, arterial hypotension, systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), bone marrow hematopoiesis suppression, hyperkalemia, condition after kidney transplantation, renal and/or hepatic insufficiency, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology III-IV functional class according to NYHA classification, decompensated heart failure, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days), elderly age, bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia, hemodialysis using high-flux dialysis membranes (AN69^®), azotemia, primary hyperaldosteronism, conditions accompanied by a decrease in circulating blood volume (CBV) (including as a result of diarrhea, vomiting); use in patients on a salt-restricted diet.

Use in Pregnancy and Lactation

Use of the drug Ekvacard^® is not recommended during pregnancy.

If pregnancy is diagnosed, administration of the drug Ekvacard^® should be discontinued as early as possible.

Use of ACE inhibitors during the second and third trimesters of pregnancy has an adverse effect on the fetus (possible marked decrease in blood pressure, renal failure, hyperkalemia, skull bone hypoplasia, intrauterine death). There are no data on negative effects of the drug on the fetus in case of use during the first trimester. Newborns and infants who were exposed to ACE inhibitors in utero should be closely observed for timely detection of marked decrease in blood pressure, oliguria, hyperkalemia.

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

Lisinopril crosses the placenta. There are no data on the penetration of lisinopril into breast milk.

There are no data indicating the excretion of amlodipine in breast milk.

However, it is known that other dihydropyridine calcium channel blockers are excreted in breast milk.

Use of the drug Ekvacard^® during breastfeeding is not recommended.

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

Use in Hepatic Impairment

With caution: hepatic insufficiency.

Use in Renal Impairment

With caution: renal insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

With caution: elderly age.

Special Precautions

Treatment with the drug Ekvacard^® can be started only after correction of hyponatremia and restoration of circulating blood volume.

After taking the first dose of the drug, careful monitoring of blood pressure is recommended; a significant decrease in blood pressure with the development of symptomatic arterial hypotension is possible. A marked decrease in blood pressure most often occurs with a decrease in circulating blood volume caused by diuretic therapy, reduced dietary salt intake, dialysis, diarrhea, or vomiting.

In case of arterial hypotension, the patient should be placed in a horizontal position and, if necessary, an intravenous solution replenishing the volume of circulating fluid should be administered (infusion of 0.9% sodium chloride solution).

Similar rules should be followed when using the drug Ekvacard^® in patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

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

During therapy with the drug Ekvacard^®, it is necessary to monitor body weight and salt intake; an appropriate diet is indicated.

Maintenance of oral hygiene and observation by a dentist is necessary (to prevent soreness, bleeding, and gingival hyperplasia).

During the therapy, periodic monitoring of peripheral blood is necessary, since the potential risk of agranulocytosis cannot be excluded; periodic monitoring of peripheral blood is required.

In case of impaired renal function, for example, with renal artery stenosis (especially bilateral or with stenosis of the arteries of a single kidney), hyponatremia, dehydration, circulatory insufficiency, taking the drug may provoke worsening of renal function and acute renal failure, which is reversible after discontinuation of treatment. Monitoring of patients with impaired renal function is necessary.

In elderly patients, the half-life of amlodipine may increase and the clearance of the drug may decrease. More careful observation of patients in this category is necessary.

In case of impaired liver function, the half-life of amlodipine increases; the drug should be prescribed with caution in such patients, after assessing the benefit and risk. When using ACE inhibitors, angioedema of the face, extremities, lips, tongue, epiglottis, or larynx may develop, requiring immediate discontinuation of treatment with the drug and medical observation until symptoms completely regress. Angioedema with laryngeal edema can be fatal. Swelling of the tongue, epiglottis, or larynx can cause airway obstruction, so appropriate therapy should be immediately administered (0.3-0.5 ml of 1:1000 epinephrine (adrenaline) solution subcutaneously) and/or measures to ensure airway patency. In cases where the edema is localized only on the face and lips, the condition most often resolves without treatment, but the use of antihistamines is possible.

The risk of developing angioedema is increased in patients with a history of angioedema from the use of ACE inhibitors.

In patients taking ACE inhibitors during desensitization procedures with hymenoptera venom, life-threatening anaphylactoid reactions can very rarely develop. This can be avoided by temporarily discontinuing ACE inhibitor treatment before each desensitization procedure for hymenoptera.

Surgery/general anesthesia: when using agents for general anesthesia with antihypertensive action and during extensive surgical interventions, Lisinopril inhibits the formation of angiotensin-II in response to compensatory renin release. In such arterial hypotension, blood pressure is normalized by increasing the circulating blood volume.

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

Anaphylactoid reactions have also been noted in patients on hemodialysis using high-flux dialysis membranes (AN69^®) who are simultaneously taking ACE inhibitors. In such cases, the possibility of using another type of dialysis membrane or another antihypertensive agent should be considered. When selecting the dose, it should be taken into account that in elderly patients, both active substances are determined in the blood in a higher concentration, while the effectiveness does not change.

A cough has been observed with the use of ACE inhibitors. The cough is dry, prolonged, and disappears after discontinuation of the ACE inhibitor. When making a differential diagnosis of cough, cough caused by the use of an ACE inhibitor should be taken into account.

Effect on ability to drive vehicles and mechanisms

Caution should be exercised when taking the drug Ekvacard^® due to the possible development of arterial hypotension, dizziness, and drowsiness, which may affect the ability to drive vehicles and operate potentially dangerous machinery.

Overdose

Lisinopril

Symptoms: marked decrease in blood pressure, dryness of the oral mucosa, water-electrolyte imbalance, renal failure, increased respiration, tachycardia, palpitation sensation, bradycardia, dizziness, anxiety, increased irritability, cough, drowsiness, urinary retention, constipation. Treatment: specific antidote is absent. Gastric lavage, use of enterosorbents and laxatives. Intravenous administration of 0.9% sodium chloride solution is indicated. In case of bradycardia resistant to treatment, the use of an artificial pacemaker is necessary. Monitoring of blood pressure, water-electrolyte balance indicators is necessary. Hemodialysis is effective.

Amlodipine

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

Treatment: gastric lavage, use of activated charcoal (especially within the first 2 hours after overdose), maintenance of cardiovascular function, elevated position of the lower extremities, monitoring of heart and lung function indicators, control of circulating blood volume and diuresis. To restore vascular tone, use of vasoconstrictors (in the absence of contraindications to their use); to eliminate the consequences of calcium channel blockade, intravenous administration of calcium gluconate. Hemodialysis is not effective.

Drug Interactions

Lisinopril

Lisinopril should be used with caution simultaneously with potassium-sparing 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 based on an individual decision by the physician with regular monitoring of serum potassium levels and renal function.

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

With simultaneous use with nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors), estrogens, as well as sympathomimetics, the antihypertensive effect of lisinopril is reduced. NSAIDs, including COX-2, and ACE inhibitors increase serum potassium levels and may impair renal function. This effect is usually reversible.

Lisinopril slows the excretion of lithium preparations, so with simultaneous use, a reversible increase in its plasma concentration occurs, which may increase the likelihood of adverse events; therefore, serum lithium concentration should be regularly monitored.

With simultaneous use with antacids and cholestyramine, the absorption of lisinopril from the gastrointestinal tract is reduced.

Ethanol enhances the effect of lisinopril.

With simultaneous use with insulin and oral hypoglycemic agents, the risk of hypoglycemia increases.

With simultaneous use of lisinopril with vasodilators, barbiturates, antipsychotic agents (neuroleptics), tricyclic antidepressants, calcium channel blockers, beta-blockers, an enhancement of the antihypertensive effect is possible. With simultaneous use of ACE inhibitors and intravenous gold preparations (sodium aurothiomalate), a symptom complex including facial flushing, nausea, vomiting, and decreased blood pressure has been described.

Concomitant use with allopurinol, procainamide, cytostatics may lead to leukopenia.

Amlodipine

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

Unlike other calcium channel blockers, no clinically significant interaction of amlodipine was found with concomitant use with NSAIDs, including indomethacin.

Enhancement of the antianginal and hypotensive effect of calcium channel blockers is possible with concomitant use with thiazide and “loop” diuretics, ACE inhibitors and nitrates, as well as enhancement of their antihypertensive effect with simultaneous use with alpha1-blockers.

Erythromycin with concomitant use increases the C_max of amlodipine in young patients by 22%, and in elderly patients by 50%.

Beta-blockers when used simultaneously with amlodipine may cause exacerbation of the course of chronic heart failure.

Although a negative inotropic effect was usually not observed in studies of amlodipine, nevertheless, some calcium channel blockers may enhance the severity of the negative inotropic effect of antiarrhythmic agents causing QT interval prolongation (for example, amiodarone and quinidine).

A single dose of 100 mg sildenafil in patients with arterial hypertension does not affect the pharmacokinetic parameters 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 pharmacokinetic parameters of atorvastatin.

Ethanol (beverages containing alcohol): Amlodipine with single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol.

Antiretroviral agents (ritonavir) increase plasma concentrations of calcium channel blockers, including amlodipine.

Neuroleptics and isoflurane enhance the hypotensive effect of dihydropyridine derivatives.

Calcium preparations may reduce the effect of calcium channel blockers.

With concomitant use of amlodipine with lithium preparations, an increase in the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) is possible.

Amlodipine does not change the pharmacokinetics of cyclosporine.

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

It does not have a significant effect on the action of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

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

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

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

Storage Conditions

Store the drug out of the reach of children, in a light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use the drug after the expiration date indicated on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.