Universal reference book for medicines
Product name: EQUAKARD (EKVACARD)

Active substance: amlodipine, lisinopril

Type: Antihypertensive drug

Manufacturer: MICRO LABS (India)
Composition, form of production and packaging
Tablets of
pink color, round, flat-cylindrical, with a facet, with a risk on one side.

1 tab.

amlodipine 5 mg

lisinopril 5 mg

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

10 pieces.
- blisters (1) - packs of cardboard.
10 pieces.
- blisters (2) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (10) - packs of cardboard.
Tablets of white color, round, flat-cylindrical, with a facet, with a risk on one side.

1 tab.

amlodipine 5 mg

lisinopril 10 mg

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

10 pieces.
- blisters (1) - packs of cardboard.
10 pieces.
- blisters (2) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
10 pieces.
- blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2013.

PHARMACHOLOGIC EFFECT

Combined drug containing active ingredients: lisinopril and amlodipine.

Lisinopril

The angiotensin-converting enzyme (ACE) inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing angiotensin II leads to a direct decrease in the release of aldosterone.
Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance (OPSS), blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to the load in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on the renin-angiotensin-aldosterone system (PALS). With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease. Improves the blood supply of the ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent acute myocardial infarction without clinical manifestations of heart failure.

The beginning of the drug after 1 hour, the maximum antihypertensive effect is achieved after 6-7 hours and persists for 24 hours. The duration of the effect also depends on the amount of the dose taken.
With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months of therapy. With a sharp reversal of lisinopril, there was no pronounced increase in blood pressure. Lizinopril reduces albuminuria. Does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.
Amlodipine

The "slow" calcium channel blocker, the dihydropyridine derivative of the "slow" calcium channel blocker (BCCI), has an antianginal and antihypertensive effect, blocks calcium channels, reduces the granemembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

Antianginal effect is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia;
expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for myocardium in oxygen. Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium, increases the 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, increases the time until the onset of an attack of angina and "ischemic" depression of the ST segment, reduces the incidence of angina attacks and the consumption of nitroglycerin and other nitrates.
Has a long-term dose-dependent antihypertensive effect.
Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient's "lying" and "standing" position). Orthostatic hypotension in the appointment of amlodipine is rare. Does not cause a decrease in the fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases the rate of glomerular filtration, has a weak natriuretic effect.
When diabetic nephropathy does not increase the severity of microalbumiuria.
Does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 h, the duration of the effect is 24 h.
Ecquard В®

The combination of lisinopril with amlodipine in a single medicine can prevent the development of possible undesirable effects caused by the contradiction of any of the active substances.
So, the blocker of the "slow" calcium channels, directly expanding the arterioles, can lead to a delay in sodium and fluid in the body, and.therefore, can activate the RAAS. The ACE inhibitor blocks this process, normalizes the reactions to the load with salts.
PHARMACOKINETICS

Lisinopril

After oral administration, lisinopril is absorbed from the gastrointestinal tract by an average of 25%, but the absorption can vary from 6 to 60%.
Bioavailability is 29%. C max in blood plasma is achieved after 7 hours. Food intake does not affect the absorption of lisinopril. Lizinopril slightly binds to blood plasma proteins.Permeability through the blood-brain and placental barrier is low.
Lizinopril 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 insufficiency (creatinine clearance less than 30 ml / min), the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, with an increase in the time to reach C max in the blood plasma and an increase in T 1/2 .

In elderly patients, the C max drug in blood plasma and AUC is 2 times greater than in young patients.

In patients with liver cirrhosis, the bioavailability of lisinopril is reduced by 30%, and the 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 ingestion, amlodipine is slowly absorbed from the digestive tract.
The average absolute bioavailability is 64%, C max in serum is observed after 6-9 hours. Equilibrium concentrations (C ss ) are achieved after 7-8 days of therapy.
The intake of food does not affect the absorption of amlodipip.
The average V d is 21 l / kg body weight, indicating that most of the drug is in the tissues, and the smaller is in the blood. Most of the amlodipine, which is in the blood (95%), binds to blood plasma proteins. Amlodipine undergoes a slow, active metabolism in the liver in the absence of a significant "primary passage" effect. Metabolites do not have significant pharmacological activity. After a single ingestion of T 1/2 , it varies from 35 to 50 hours, with repeated use T 1/2 is approximately 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 / c / kg (7 ml / min / kg, 0.42 l / h / kg).
In elderly patients (over 65 years), amlodipine withdrawal is slowed (T 1/2 is 65 hours) compared with young patients, but this difference is not clinically significant.Elongation of T 1/2 in patients with hepatic insufficiency suggests that with prolonged use, cumulation of the drug in the body will be higher (T 1/2 to 60 h).
Renal failure does not significantly affect the kinetics of amlodipine. In patients with impaired renal function, changes in amlodipine and plasma concentrations are not correlated with the degree of renal failure. A slight increase in T 1/2 is possible.
Amlodipine penetrates the blood-brain barrier.
When hemodialysis is not removed.
Ecquard В®

Pharmacokinetic interaction between active ingredients in the formulation is unlikely.
AUC, the time of reaching and the values ​​of C max , T 1/2 do not undergo changes in comparison with the indices of each individual active substance. Eating does not affect the absorption of active substances. Long circulation in the body of both active substances makes it possible to take the drug 1 time / day.
INDICATIONS

- Essential hypertension (patients who are shown combined therapy).

DOSING MODE

Tablets of the drug Ecquard В® are taken orally once a day, regardless of the time of eating, squeezed with enough liquid.

Adults

The recommended dose is 1 tablet of the drug Ecquard В® 1 time / day.
At the beginning of therapy with the drug Ecquard В® , symptomatic arterial hypotension may develop, which often occurs in patients with disturbances of the water-electrolyte balance due to previous therapy with diuretics. Diuretics should be discontinued 2-3 days before therapy with Ecquard В® is started.
In cases where the elimination of diuretics is not possible, the initial dose of the drug Ecquard В® is 1/2 tablet (5 mg + 5 mg) 1 time / day, after taking it, for several hours should be monitored for the patient due to the possible development of symptomatic arterial hypotension.

Renal impairment

In patients with impaired renal function, it is recommended to use the drug Ecuquard В® at a dose of 5 mg + 5 mg (an increase in T 1/2 of lisinopril).
The maintenance dose is selected depending on the tolerability of the therapy, it is required to monitor the function of the kidneys, the content of potassium and sodium in the blood plasma.
Dysfunction of the liver

In patients with impaired hepatic function it is recommended to use the drug Ecquard В® in a dose of 5 mg + 5 mg (increase T 1/2 amlodipine).

SIDE EFFECT

The frequency of adverse reactions listed below was determined according to the following (classification of the World Health Organization): 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 reports.
Lisinopril

From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension;
infrequently - acute myocardial infarction, tachycardia, palpitation; Raynaud's syndrome; rarely bradycardia, tachycardia, aggravation of symptoms of chronic heart failure, violation of atrioventricular conduction, chest pain.
From the side of the central nervous system: often - dizziness, headache;
infrequently - lability of mood, paresthesia, sleep disturbance, stroke; rarely - confusion, asthenic syndrome, convulsive twitching of the muscles of the limbs and lips, drowsiness.
On the part of the system of hematopoiesis 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;
infrequently - rhinitis; very rarely - sinusitis, bronchospasm, allergic alveolitis / eosinophilic pneumonia, dyspnea.
On the part of the digestive system: often - diarrhea, vomiting;
infrequently - indigestion, changes in taste, abdominal pain; rarely dryness of the oral mucosa; very rarely - pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis, hepatic insufficiency, interstitial edema, anorexia.
From the skin: rarely - skin itching, rash;
rarely - angioedema, swelling of the face, limbs, lips, tongue, larynx, urticaria, alopecia, psoriasis; very rarely-increased sweating, vasculitis, pemphigus, photosensitivity, toxic epidermal necrolysis (Lyell'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 side of the reproductive system: infrequently - impotence, rarely - gynecomastia.

From the side of metabolism: very rarely - hypoglycemia.

On the part of laboratory indicators: infrequently - increased urea concentration in the blood, hypercreatininaemia, hyperkalemia, increased activity of "liver" transaminases, rarely - hyperbilirubinemia, hyponatremia, increased erythrocyte sedimentation rate, false positive results of the test for antinuclear antibodies.

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

Amlodipine

From the side of the central nervous system: often - headache (especially at the beginning of treatment), dizziness, fatigue, snotty;
infrequent - general malaise, hypoesthesia, asthenia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, increased excitability, depression, anxiety, increased sweating; rarely - cramps, apathy, agitation; very rarely - ataxia, amnesia.
From the digestive system: often - nausea, abdominal pain;
infrequent - vomiting, changing the mode of defecation (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - pancreatitis, gastritis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of "liver" transaminases, hepatitis.
From the cardiovascular system: often - peripheral edema (ankles and feet), a feeling of palpitations, "hot flashes" of blood to the skin of the face;
infrequently - excessive reduction of blood pressure, orthostatic hypotension, vasculitis; rarely - development or aggravation of the course of chronic heart failure; very rarely - fainting, shortness of breath, heart rhythm disturbances (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, pulmonary edema, migraine.
From the hemopoietic and lymphatic systems: very rarely - thrombocytopenic purpura, leukopenia, thrombocytopenia.

From the urinary system: infrequently - pollakiuria, painful urge to urinate, nocturia;
very rarely - dysuria, polyuria.
On the part of the reproductive system and mammary glands: infrequently - gynecomastia, impotence.

From the respiratory system: infrequently - dyspnea, rhinitis;
very rarely - cough.
From the musculoskeletal system: infrequently - muscle cramps, myalgia.
arthralgia, back pain, arthrosis; rarely - myasthenia gravis.
From the skin: rarely - alopecia: rarely - dermatitis;
very rarely - alopecia, xeroderma, cold sticky sweat, a violation of skin pigmentation.
Allergic reactions: rarely - skin itching, rash (including erythematous, maculopapular rash);
very rarely - hives, angioedema, erythema multiforme.
From the senses: infrequent - ringing in the ears, visual impairment, diplopia, disruption of accommodation, xerophthalmia, conjunctivitis, pain in the eyes;
very rarely - parosmia.
From the side of metabolism: very rarely - hyperglycemia.

Other: infrequent - weight loss, weight gain, taste distortion, epistaxis, chills.

CONTRAINDICATIONS

- hypersensitivity to any of the components of the drug or to other derivatives of dihydropyridine, other ACE inhibitors;

- angioedema in history, including those caused by the use of other ACE inhibitors;

- hereditary and / or idiopathic angioedema;

- hemodynamically significant stenosis of the aorta or mitral valve or hypertrophic obstructive cardiomyopathy;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- cardiogenic shock;

- pregnancy, lactation;

- age up to 18 years;

- Acute myocardial infarction (within the first 28 days), unstable angina (with the exception of Prinzmetal angina);

- lactose intolerance, lactose deficiency and glucose-galactose malabsorption.

With care: cerebrovascular diseases (including cerebrovascular insufficiency), coronary insufficiency, arterial hypotension, systemic diseases of connective tissue (including scleroderma, systemic lupus erythematosus), oppression of bone marrow hematopoiesis, hyperkalemia, condition after transplantation kidney, renal and / or hepatic insufficiency, sinus node weakness syndrome (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology of III-IV functional
(after the first 28 days), elderly age, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, hemodialysis using high-flow dialysis membranes (AN69 В® ), azotemia, primary hyperaldosteronism, conditions accompanied by a decrease in the volume of circulating blood (BCC) (including as a result of diarrhea, vomiting); use in patients on a diet with restriction of table salt.
PREGNANCY AND LACTATION

Use of the drug Ecquard В® is not recommended during pregnancy.

When diagnosing a pregnancy, taking EcacardВ® should be stopped as soon as possible.

Admission of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death).
Information about the negative effects of the drug on the fetus when used during the I trimester there. For newborns and infants who have been exposed to intrauterine ACE inhibitor should be closely monitored for timely detection of significant decrease in blood pressure, oliguria and hyperkalemia.
Safety of application of amlodipine during pregnancy has not been established, therefore use during pregnancy is possible only when the benefit to the mother outweighs the potential risk to the fetus.
Lisinopril crosses the placenta. No data on the penetration of lisinopril passes into breast milk.
There is no evidence on the allocation of amlodipine passes into breast milk.
However, we know that other BCCI - dihydropyridine derivatives are excreted in breast milk.
Application Ekvakard preparation В® breastfeeding is not recommended.
If use of the drug is necessary during lactation, the breast-feeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER

With caution: kidney failure.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

With caution: liver failure.

APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

APPLICATION IN ELDERLY PATIENTS

With caution: the elderly.

SPECIAL INSTRUCTIONS

Treatment with Ekvakard В® can begin only after hyponatremia and restore circulating blood volume correction.
After receiving the first dose is recommended careful monitoring of blood pressure, may be a significant reduction in blood pressure with the development of symptomatic hypotension. In most pronounced decrease in blood pressure occurs with a decrease in CBV induced by therapy with diuretics, reduction of salt content in food, dialysis, vomiting or diarrhea.
If hypotension patient attach a horizontal position and if appropriate in / injected solution, granting you volume of the circulating fluid (infusion of 0.9% sodium chloride solution).
Such rules should be followed when using the drug Ekvakard В®Patients with coronary artery disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to heart attack or stroke.
When aortic stenosis, hypertrophic obstructive cardiomyopathy appointment vasodilator requires caution.
During therapy with Ekvakard В® necessary to control body weight and salt intake, shows the assignment of an appropriate diet.
It is necessary to maintain oral hygiene and dental observation y (to prevent pain, bleeding and gingival hyperplasia).
During the therapy requires periodic monitoring of peripheral blood, as we can not exclude the potential risk of agranulocytosis, requires periodic monitoring of peripheral blood.
If the kidney function, such as renal artery stenosis (especially bilateral stenosis or artery only kidneys), hyponatremia, dehydration, circulatory failure, the drug can cause renal impairment and acute renal failure, reversible after cessation of treatment. Necessary to monitor patients with impaired renal function.
Elderly patients may be increased T 1/2 amlodipine and decrease the clearance of the drug. The need for closer monitoring of patients in this category.
In human liver increases the half-life of amlodipine, such drug prescribed to patients with caution after use and risk assessment. When the use of ACE inhibitors may angioedema of the face, extremities, lips, tongue, epiglottis, or larynx requires immediate cessation of drug treatment and the establishment of medical supervision until complete regression of symptoms. Angioedema with laryngeal edema can be fatal. Edema language epiglottis or larynx may be the cause of airway obstruction, however, immediately implement appropriate therapy (0.3-0.5 ml of a 1: 1000 solution of epinephrine (adrenaline) n / k) and / or measures pi ensure airway patency. In cases where the swelling is localized only on the face and lips, the condition often goes untreated,but it is possible the use of antihistamines.
The risk of angioedema increased in patients who have a history of angioneurotic edema by ACE inhibitors.
Patients receiving ACE inhibitors during desensitization procedure Hymenoptera venom is extremely rare, can develop life-threatening anaphylactoid reactions. This can be avoided by temporarily discontinue treatment with an ACE inhibitor prior to each desensitization procedure na gimenopteru.
Surgery / general anesthesia: the means for applying general anesthesia with antihypertensive action and during major surgery lisinopril inhibits the formation of angiotensin-II in response to compensatory renin release. With such a blood pressure hypotension normalized by increasing the circulating blood volume.
Prior to surgery (including dental surgery) should inform the surgeon / anesthetist on the use of an ACE inhibitor.
Anaphylactoid reactions observed in patients undergoing hemodialysis vysokoprotochnyh using a dialysis membrane (AN69 В® ), which are simultaneously taking ACE inhibitors. In such cases it is necessary to consider the possibility of using a different type of dialysis membrane or other antihypertensive agents. When selecting the dose should be noted that in elderly patients, both active ingredients are determined by the blood at a higher concentration, the efficiency is not changed.
With the use of ACE inhibitors coughing was observed. Cough dry, long, which disappear after cessation of treatment with an ACE inhibitor. The differential diagnosis of cough should be considered, and cough caused by the use of an inhibitor of APF.
Effect on vehicle management ability and mechanisms
should be cautious when receiving Ekvakard preparation В® due to the fact that the possible development of hypotension, dizziness and drowsiness, which may affect the ability to drive vehicles and working with potentially dangerous machinery.
OVERDOSE

Lisinopril
Symptoms: marked reduction of blood pressure, the dryness of the oral mucosa, disruption of water-electrolyte balance, renal insufficiency, increased respiration, tachycardia, palpitations, bradycardia, dizziness, anxiety, irritability, cough, drowsiness, urinary retention, and constipation. Treatment: the specific antidote is available. Gastric lavage, application enterosorbents and laxatives. It is shown in / in a 0.9% sodium chloride solution. In the case of bradycardia resistant to treatment, requires the use of an artificial pacemaker. Necessary to monitor blood pressure, indicators of water and electrolyte balance.
Hemodialysis is effective.
Amlodipine

Symptoms: marked reduction of blood pressure with possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent hypotension, including the development of shock and death).
Treatment: gastric lavage, administration of activated carbon (especially in the first 2 hours after the overdose), maintaining the function of the cardiovascular system, raised position the lower extremities, monitoring parameters of the heart and lungs, control circulating blood volume (CBV) and diuresis. To restore
vascular tone application vasoconstrictors (in the absence of contraindications for their use); to eliminate the effects of calcium channel blockade in / in a calcium gluconate.
Hemodialysis is not effective.
DRUG INTERACTION

Lisinopril
Caution should be used in conjunction with lisinopril potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations, salt substitutes containing potassium, cyclosporin - increases the risk of hyperkalemia, especially with impaired renal function. Therefore, these combinations should be used only on the basis of the individual solutions at regular physician monitoring the potassium content in blood serum and renal function.
When applied simultaneously with diuretics and other hypotensive agents antihypertensive effect of lisinopril amplified.
While the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2)), estrogen and sympathomimetics reduced antihypertensive effect of lisinopril. NSAIDs, including COX-2, and ACE inhibitors increase the content of potassium in blood serum and can worsen renal function. This effect is usually reversible.
Lisinopril slows excretion of lithium preparations, therefore, while the application is reversible increase in its concentration in blood plasma, which may increase the likelihood of adverse events, so you should regularly monitor the serum lithium concentration.
While the use of antacids and wheels tirami prefecture reduced absorption of lisinopril ZHK'G.
Ethanol increases the effects of lisinopril.
While the use of insulin and hypoglycemic agents for intake increases the risk of hypoglycemia.
When applied simultaneously with lisinopril vasodilators, barbiturates, antipsychotics (neuroleptics) tricyclic antidepressants.
BCCI, beta-blockers may increase the antihypertensive effect. With simultaneous use of ACE inhibitors and gold preparations / v (sodium aurotiamalat) describes a symptom, including facial flushing, nausea, vomiting and reduced blood pressure.
Joint application with allopurinol, procainamide, cytostatics can lead to leukopenia.
Amlodipine

Amlodipine can be safely used for the therapy of hypertension with thiazide diuretics, alpha-blockers or ACE inhibitors.
Unlike other BCCI amlodipine clinically significant interaction was observed when combined with the use of NSAIDs, including indomethacin.
May increase antianginal and hypotensive action BCCI when combined with thiazide and "loop" diuretics, ACE inhibitors and nitrates, as well as strengthening their antihypertensive effect, while the use of alpha1 adrenoblokatorami.
Erythromycin is a joint application increases the C max of amlodipine in younger patients by 22%, and in elderly patients - 50%.
Beta-blockers while the use of amlodipine may be caused, exacerbation of congestive heart failure.
Although the study of amlodipine negative inotropic action is usually not observed, nevertheless, some BCCI may increase the severity of the negative inotropic effects of antiarrhythmic agents causing the lengthening of the interval QT (e.g., amiodarone and quinidine).
A single dose of 100 mg sildenafil in patients with arterial hypertension has no effect on the pharmacokinetic parameters of amlodipine.
Povtornoe amlodipine 10 mg and atorvastatin 80 mg is not accompanied by a significant change in the pharmacokinetics of atorvastatin.
Ethanol (drinks containing alcohol): amlodipine with single and repeated administration in a dose of 10 mg did not affect the pharmacokinetics of ethanol.
Antiretroviral drugs (ritonavir) increase the plasma concentrations of BCCI, including amlodipine.
Neuroleptics and isoflurane increased hypotensive action of dihydropyridine derivatives.
Calcium can reduce the effect of BCCI.
When the joint application of amlodipine with lithium preparations may increase neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, noise and ears).
Amlodipine does not change the pharmacokinetics of cyclosporine.

It has no effect on serum digoxin concentration and its renal clearance.
Has no significant effect on the effect of warfarin (prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In in vitro studies, amlodipine did not affect the binding to plasma proteins, digoxin, phenytoin, warfarin and indomethacin.
Grapefruit juice: simultaneous single dose of 240 mg of grapefruit juice and 10 mg amlodipine inwardly not accompanied by a significant change in the pharmacokinetics of amlodipine.
Aluminum- or magnesium-containing antacids: their single dose has no significant effect on the pharmacokinetics of amlodipine.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of the reach of children, protected from light, at a temperature of no higher than 25 В° C.

Shelf life - 3 years.
Do not use the drug after the expiry date indicated pa package.
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