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Amlodipine, Lisinopril

Micro Labs Ltd
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2019-09-19
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Clinical Pharmacology

Equacard is a combined preparation containing active ingredients: lisinopril and amlodipine.
Lisinopril
Angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases prostaglandin synthesis. Reduces total peripheral vascular resistance (OPSS), blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increase the tolerance of the myocardium to the load in patients with chronic heart failure. Expands arteries to a greater extent than veins. Some effects are attributed to effects on the renin-angiotensin-aldosterone system (RALS). With prolonged use, hypertrophy of the myocardium and the walls of resistive arteries is reduced. Improves blood supply to ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients after acute myocardial infarction without clinical manifestations of heart failure.
The onset of action of the drug after 1 h, the maximum antihypertensive effect is achieved after 6-7 hours and lasts for 24 hours. The duration of the effect also depends on the size of the dose taken. In case of arterial hypertension, the effect is noted in the first days after the start of treatment, a stable action develops after 1-2 months of therapy. With abrupt cancellation of lisinopril, no pronounced increase in blood pressure was observed. Lisinopril reduces albuminuria. Does not affect the concentration of glucose in the blood of patients with diabetes mellitus and does not lead to an increase in cases of hypoglycemia.
Amlodipine
The “slow” calcium channel blocker, a dihydropyridine derivative of the “slow” calcium channel blocker (BMCC), has antianginal and antihypertensive effects, blocks calcium channels, reduces the granulome-calcium transition of calcium ions into the cell (to a greater extent in vascular smooth muscle cells than in cardiomyocytes).
Antianginal action due to the expansion of the coronary and peripheral arteries and arterioles: with angina reduces the severity of myocardial ischemia; expanding peripheral arterioles, reduces the round focal disease, reduces the afterload on the heart, reduces the need for myocardium in oxygen. Expanding the coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the flow of oxygen to 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 before the onset of an attack of angina and “ischemic” depression of the ST segment, reduces the frequency of attacks of stenocardia and the 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 vascular smooth muscle. In case of arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient's position "lying" and "standing".) Orthostatic hypotension when prescribing amlodipine is quite rare. Does not cause a decrease in the left ventricular ejection fraction. Decreases the degree of hypertrophy left ventricular myocardium. 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 the metabolism and plasma lipid concentration and can be used in the treatment of patients with bronchial asthma, diabetes and gout. A significant decrease in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

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Indications

Essential hypertension (for patients who are recommended combination therapy).

Composition

1 tablet contains amlodipine 5 mg, lisinopril 10 mg.

Amlodipine, Lisinopril is marketed under different brands and generic names, and comes in different dosage forms:

Brand nameManufacturerCountryDosage form
Equacard Micro Labs Ltd India pills
Equator Gedeon Richter Hungary pills

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Amlodipine, Lisinopril

Dosage and Administration

pills of the drug Equacard are taken orally once a day, regardless of the time of meals, drinking plenty of fluids.
Adults
The recommended dose is 1 tablet of the drug Equacard 1 time / day. At the beginning of therapy with Equacard, symptomatic arterial hypotension may develop, which occurs more often in patients with impaired water and electrolyte balance due to previous diuretic therapy. The admission of diuretics should be discontinued 2-3 days before the start of therapy with Equacard.
In cases where the cancellation of diuretics is impossible, the initial dose of Equacardum is 1/2 tablet (5 mg + 5 mg) 1 time / day, after which, patient should be monitored for several hours after possible symptomatic arterial development. hypotension.

Adverse reactions

The frequency of adverse reactions listed below was determined accordingly to the following (classification of the World Health Organization): very often - at least 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

Since the cardiovascular system: often - pronounced decrease in blood pressure, orthostatic hypotension; infrequently - acute myocardial infarction, tachycardia, palpitations; Raynaud's syndrome; rarely - bradycardia, tachycardia, aggravation of symptoms of chronic heart failure, impaired atrioventricular conduction, chest pain.

From the side of the central nervous system: often - dizziness, headache; infrequently - mood lability, paresthesias, sleep disorders, stroke; rarely - confusion, asthenic syndrome, convulsive muscle twitching of the limbs and lips, drowsiness.

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

On the part of the respiratory system: often cough; infrequently - 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: infrequently - pruritus, rash; rarely - angioedema of the face, extremities, lips, tongue, larynx, urticaria, alopecia, psoriasis; very rarely, excessive sweating, vasculitis, pemphigus, photosensitivity, toxic epidermal necrolysis (Layel syndrome), erythema multiforme, Stevens-Johnson syndrome.

From the urinary system: often - impaired renal function; infrequently - uremia, acute renal failure; very rarely - anuria, oliguria, proteinuria.

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

Metabolism: very rarely - hypoglycemia.

From the laboratory indicators: infrequently - an increase in blood urea concentration, hypercreatininemia, hyperkalemia, increased activity of “liver” 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 side of the central nervous system: often - headache (especially at the beginning of treatment), dizziness, fatigue, drowsiness; infrequently - general malaise, hypesthesia, asthenia, paresthesia, peripheral neuropathy, tremor, insomnia, emotional lability, unusual dreams, nervousness, anxiety, depression, anxiety, increased sweating; rarely - convulsions, apathy, agitation; very rarely - ataxia, amnesia.

From the digestive system: often - nausea, abdominal pain; infrequently - vomiting, change of 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.

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

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

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

From the reproductive system and mammary glands: infrequently - gynecomastia, impotence.

On the part of the respiratory system: infrequently - shortness of breath, rhinitis; very rarely - cough.

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

Skin Covers: infrequently - alopecia: rarely - dermatitis; very rarely - alopecia, xeroderma, cold sticky sweat, impaired skin pigmentation.

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

From the senses: infrequently - tinnitus, blurred vision, diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, eye pain; very rarely - parosmia.

Metabolism: very rarely - hyperglycemia.

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

Contraindications

  • hypersensitivity to any of the components of the drug or to other derivatives of dihydropyridine, 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 aorta or mitral valve or hypertrophic obstructive cardiomyopathy;
  • severe hypotension (systolic blood pressure less than 90 mm Hg);
  • cardiogenic shock;
  • pregnancy, lactation;
  • age up to 18 years;
  • acute myocardial infarction (during the first 28 days), unstable angina (with the exception of Prinzmetal stenocardia);
  • lactose intolerance, lactose deficiency and glucose-galactose malabsorption.

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 in case of impaired kidney function. Therefore, these combinations should be used only on the basis of an individual physician's decision with regular monitoring of serum potassium and kidney function.
With simultaneous use with diuretics and other antihypertensive drugs, the antihypertensive effect of lisinopril is enhanced.
With simultaneous use with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors (COX-2)), 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 kidney function. This effect is usually reversible.
Lisinopril slows down the excretion of lithium preparations, therefore, with simultaneous use, there is a reversible increase in its concentration in the blood plasma, which can increase the likelihood of developing adverse events, so you should regularly monitor the concentration of lithium in the blood serum.
With simultaneous use with antacids and tyramine wheels, the absorption of lisinopril from GHG decreases.
Ethanol enhances the effect of lisinopril.
When used simultaneously with 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-adrenergic blockers may enhance the antihypertensive effect. With the simultaneous use of ACE inhibitors and gold preparations in / in (sodium aurothiamalate), a symptom complex is described, including facial flushing, nausea, vomiting, and a decrease in blood pressure.
Combined use with allopurinol, procainamide, cytostatics can lead to leukopenia.
Amlodipine
Amlodipine can be safely used for the treatment of arterial hypertension along with thiazide diuretics, alpha-blockers or ACE inhibitors.
Unlike other AMCCs, clinically significant interaction of amlodipine was not found when used together with NSAIDs, including indomethacin.
It is possible to enhance the antianginal and hypotensive effects of BMCA when used together with thiazide and “loop” diuretics, ACE inhibitors and nitrates, as well as enhancing their antihypertensive action while using alpha1-adrenergic blockers.
When used together, erythromycin increases amlodipine Cmax in young patients by 22% and in elderly patients by 50%.
Beta-blockers when used simultaneously with amlodipine may be caused, exacerbation of chronic heart failure.
Although in the study of amlodipine, a negative inotropic effect was usually not observed, however, some BMCCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (eg, amiodarone and quinidine).
A single dose of 100 mg of sildenafil in patients with arterial hypertension does not affect the parameters of amlodipine pharmacokinetics.
The 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 (alcohol-containing beverages): Amlodipine, when taken once and repeated at a dose of 10 mg, does not affect the pharmacokinetics of ethanol.
Antiretrovirals (ritonavir) increases plasma concentrations of BCCA, including amlodipine.
Neuroleptics and isoflurane enhance the hypotensive action of dihydropyridine derivatives.
Calcium preparations can reduce the effect of BCCA.
The combined use of amlodipine with lithium preparations may increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, noise and ears).
Amlodipine does not alter the pharmacokinetics of cyclosporine.
Does not affect the concentration of serum digoxin and its renal clearance.
It has no 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 binding to plasma proteins, digoxin, phenytoin, warfarin, and indomethacin.
Grapefruit juice: a single dose 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 dose does not have a significant effect on the pharmacokinetics of amlodipine.

Pregnancy and Lactation

The use of the drug Equacard is not recommended during pregnancy.
When diagnosing pregnancy, taking the drug Equacard should be stopped as soon as possible.
Acceptance of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (pronounced decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death) are possible. Data on the negative effects of the drug on the fetus in the case of use during the first trimester is not. It is recommended to carefully monitor newborns and infants who have undergone intrauterine effects of ACE inhibitors, in order to timely detect a pronounced decrease in blood pressure, oliguria, and 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 penetrates through the placenta. There is no data on the penetration of lisinopril into breast milk.
There are no data indicating the release of amlodipine in breast milk.
However, it is known that other BCCA - dihydropyridine derivatives, are excreted in breast milk.
The use of the drug Equacard® in the period of breastfeeding is not recommended.
If the use of the drug is necessary during lactation, breastfeeding should be stopped.

Special instructions

Treatment with Equacard can be started only after correction of hyponatremia and restoration of circulating blood volume.
After taking the first dose of the drug, careful control of blood pressure is recommended, a significant decrease in blood pressure with the development of symptomatic arterial hypotension is possible. Most often, a pronounced decrease in blood pressure occurs with a decrease in BCC, caused by diuretic therapy, a decrease in the content of table salt in food, dialysis, diarrhea or vomiting.
In case of arterial hypotension, the patient is given a horizontal position and, if necessary, a solution is introduced in / in to fill the volume of the circulating fluid (infusion of 0.9% sodium chloride solution).
Similar rules should be followed when using the drug Ekvakard patients with coronary artery disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
With aortic stenosis, hypertrophic obstructive cardiomyopathy, the administration of a vasodilator requires caution.
During the period of therapy with Equacard®, it is necessary to control body weight and salt intake, the purpose of the appropriate diet is shown.
It is necessary to maintain oral hygiene and observation at the dentist (to prevent pain, bleeding and gingival hyperplasia).
During the period of 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, in renal artery stenosis (especially bilateral or in arterial stenosis of a single kidney), hyponatremia, dehydration, circulatory failure, taking the drug can cause deterioration of renal function and acute renal failure, reversible after treatment is stopped. Monitoring of patients with impaired renal function is necessary.
Elderly patients may increase amlodipine T1 / 2 and reduce the clearance of the drug. Need more careful monitoring of patients in this category.
If liver function is abnormal, the half-life of amlodipine increases, so patients are prescribed the drug with caution, after evaluating the benefits and risks. When using ACE inhibitors, it is possible to develop angioedema of the face, extremities, lips, tongue, epiglottis or larynx, requiring immediate cessation of drug treatment and the establishment of medical observation until the full regression of symptoms. Angioedema with laryngeal edema can be fatal. Swelling of the tongue, epiglottis, or larynx can be the cause of airway obstruction, therefore, it is necessary to immediately carry out appropriate therapy (0.3-0.5 ml of 1: 1000 solution of epinephrine (adrenaline) s / c) and / or measures to ensure the airway patency. In cases where edema is localized only on the face and lips, the condition most often disappears without treatment, however, it is possible to use antihistamines.
The risk of developing angioedema increases in patients who have a history of angioedema due to the use of ACE inhibitors.
Patients taking ACE inhibitors during the desensitization procedure for hymenoptera poison, extremely rarely, can develop life-threatening anaphylactoid reactions. This can be avoided by temporarily stopping the treatment with an ACE inhibitor before each desensitization procedure on the bimenopter.
Surgical intervention / general anesthesia: when using agents for general anesthesia with antihypertensive effects and when performing extensive surgical interventions, lisinopril inhibits the formation of angiotensin-II in response to compensatory renin secretion. With such arterial hypotension, blood pressure is normalized by increasing the volume of circulating blood.
Before surgery (including dental surgery), the surgeon / anesthetist 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), who simultaneously take ACE inhibitors. In such cases, it is necessary to consider the possibility of using another type of membrane for dialysis or another antihypertensive agent. When selecting the dose, it should be borne in mind that in elderly patients both active substances are determined in the blood in greater concentration, and the effectiveness does not change.
When using ACE inhibitors, cough was noted. The cough is dry, long-lasting, which disappears after stopping treatment with an ACE inhibitor. In the differential diagnosis of cough, cough caused by the use of an ACE inhibitor should also be considered.

Overdosage

Lisinopril
Symptoms: a pronounced decrease in blood pressure, dryness of the oral mucosa, impaired water and electrolyte balance, renal failure, increased breathing, tachycardia, feeling of heartbeat, bradycardia, dizziness, anxiety, irritability, coughing, drowsiness, urinary retention, constipation.
Treatment: no specific antidote. Gastric lavage, the use of enterosorbents and laxatives. Shown in / in the introduction of a 0.9% solution of sodium chloride. In the case of treatment-resistant bradycardia, an artificial pacemaker should be used. Need to control blood pressure, indicators of water and electrolyte balance. Hemodialysis is effective.
Amlodipine
Symptoms: a pronounced decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of severe and persistent arterial hypotension, including the development of shock and death).
Treatment: gastric lavage, the use of activated carbon (especially in the first 2 hours after an overdose), maintaining the function of the cardiovascular system, the elevated position of the lower extremities, monitoring the performance of the heart and lungs, monitoring circulating blood volume (BCC) and diuresis. Recovery
vascular tone; use of vasoconstrictor agents (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade in / in the introduction of calcium gluconate. Hemodialysis is not effective.

  • Brand name: Equacard
  • Active ingredient: Amlodipine, Lisinopril
  • Dosage form: Pills.
  • Manufacturer: Micro Labs Ltd
  • Country of Origin: India

Studies and clinical trials of Amlodipine, Lisinopril (Click to expand)

  1. Long-term hemodynamic effects at rest and during exercise of newer antihypertensive agents and salt restriction in essential hypertension: Review of epanolol, doxazosin, amlodipine, felodipine, diltiazem, lisinopril, dilevalol, carvedilol, and ketanserin
  2. Cost-effectiveness of Chlorthalidone, Amlodipine, and Lisinopril as First-step Treatment for Patients with Hypertension: An Analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
  3. Effects of lisinopril and amlodipine on microalbuminuria and renal function in patients with hypertension
  4. Differences between amlodipine and lisinopril in control of clinic and twenty-four hour ambulatory blood pressures
  5. Simultaneous Determination of Amlodipine-Enalapril Maleate and Amlodipine-Lisinopril in Combined Tablet Preparations by Derivative Spectrophotometry
  6. Outcomes in Hypertensive Black and Nonblack Patients Treated With Chlorthalidone, Amlodipine, and Lisinopril
  7. Antiproteinuric effect of lisinopril and amlodipine in nondiabetic subjects: a double-blind, randomised prospective study: J.J.W.M. Janssen, R.O.B. Gans, J. van der Meulen, R. Pijpers, P.M. ter Wee. Department of Nephrology, Free University Hospital, Amsterdam, Netherlands
  8. Antiproteinuric effect on lisinopril and amlodipine
  9. Risk of cardiovascular events with amlodipine, lisinopril, or valsartan therapy in hypertension population
  10. Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension
  11. Effects of lisinopril and amlodipine on antioxidant status in experimental hypertension
  12. Comparison between the effects of amlodipine and lisinopril on proteinuria in nondiabetic renal failure: A double-blind, randomized prospective study
  13. Monotherapy treatment success rate of omapatrilat, a vasopeptidase inhibitor, compared with lisinopril and amlodipine in mild to moderate hypertension
  14. Lack of effect of short-term treatment with Amlodipine and Lisinopril on retinal autoregulation in normotensive patients with type 1 diabetes and mild diabetic retinopathy
  15. Sub-Acute Effects of Blood Pressure Lowering with Amlodipine or Lisinopril on Local Carotid Artery Haemodynamics
  16. Amlodipine vs lisinopril for BP: the choice is yours
  17. Amlodipine, lisinopril and intima-media thickness in hypertension
  18. Long-term treatment with either amlodipine or lisinopril reduces left ventricular mass in elderly patients with hypertension
  19. Amlodipine/hydrochlorothiazide/lisinopril overdose
  20. Effects of Lisinopril, Irbesartan, and Amlodipine on the Thrombogenic Variables in the Early and Late Stages of the Treatment in Hypertensive Patients
  21. Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT
  22. Effects of Amlodipine and Lisinopril on Left Ventricular Mass and Diastolic Function in Previously Untreated Patients with Mild to Moderate Diastolic Hypertension
  23. A Comparative Study of the Efficacy and Tolerability of Amlodipine and Lisinopril in the Treatment of Essential Hypertension
  24. Amlodipine/enalapril/lisinopril

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