Equacard, tablets 5 mg+10 mg 30 pcs

Equacard is a combination drug containing the active ingredients: lisinopril and amlodipine.

Lisinopril

An angiotensin-converting enzyme (ACE) inhibitor, reduces angiotensin II formation from angiotensin I. Decreased angiotensin II leads to a direct decrease in aldosterone release. Reduces bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance (TPR), BP, preload, pulmonary capillary pressure, causes an increase in the minute blood volume and increases myocardial tolerance to load in patients with chronic heart failure. Dilates arteries more than veins. Some effects are attributed to effects on the renin-angiotensin-aldosterone system (RALS). Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. It improves blood supply of ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, delay progression of left ventricular dysfunction in patients who have had acute myocardial infarction without clinical manifestations of heart failure.

The onset of action of the drug in 1 hour, the maximum antihypertensive effect is achieved in 6-7 hours and lasts for 24 hours. The duration of the effect also depends on the amount of dose taken. In arterial hypertension, the effect is noted in the first days after treatment start, a stable effect develops after 1-2 months of therapy. When lisinopril is abruptly withdrawn, no marked increase in BP has been observed. Lisinopril reduces albuminuria. It does not affect blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.

Amlodipine

. Slow calcium channel blocker, a dihydropyridine derivative slow calcium channel blocker (BMCC), has antianginal and antihypertensive effects, blocks calcium channels, reduces the granemembrane transition of calcium ions into the cell (more in vascular smooth muscle cells than in cardiomyocytes).

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

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilatory effect on vascular smooth muscle. In arterial hypertension a single dose provides clinically significant BP reduction for 24 hours (in patient “lying” and “standing”). Orthostatic hypotension when prescribing amlodipine is rare. It does not cause reduction of left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy. It does not affect myocardial contractility and conduction, does not cause reflex increase in HR, inhibits platelet aggregation, increases glomerular filtration rate, 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 concentration of plasma lipids and can be used for therapy of patients with bronchial asthma, diabetes mellitus and gout. Significant decrease in BP is observed after 6-10 hours, the duration of effect is 24 hours.

Indications

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

Active ingredient

Composition

1 tablet contains amlodipine 5 mg,

lisinopril 10 mg.

How to take, the dosage

Equacard tablets are taken orally once a day regardless of the time of meals, with plenty of fluids.

Adults
The recommended dose is 1 tablet of Equacard once daily. At the beginning of therapy with Equacard could develop symptomatic arterial hypotension which usually occurs in patients with water-electrolyte balance disorders caused by previous therapy with diuretics. Diuretics should be discontinued 2-3 days prior to the start of therapy with the drug Equacard.

In cases when diuretics cannot be stopped the initial dose of Equacard is 1/2 tablet (5 mg + 5 mg) 1 time per day, after its administration the patient should be under supervision for several hours because of possible development of symptomatic arterial hypotension.

Interaction

Lisinopril
Caution should be exercised when using lisinopril concomitantly with potassium-saving 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 a physician with regular monitoring of serum potassium and renal function.
With concomitant use with diuretics and other hypotensive agents, the antihypertensive effect of lisinopril is enhanced.

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

Lisinopril slows excretion of lithium preparations, therefore concomitant use causes reversible increase of its concentration in plasma, which may increase the risk of adverse events, therefore serum lithium concentration should be monitored regularly.

Concomitant use with antacids and pills decreases absorption of lisinopril from GI’H.
Ethanol increases the effect of lisinopril.

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

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

BMCs, beta-adrenoblockers may increase the antihypertensive effect. When concomitant use of ACE inhibitors and intravenous gold drugs (sodium aurothiamalate), a symptomcomplex including facial hyperemia, nausea, vomiting and BP decrease has been described.

Co-administration with allopurinol, procainamide, cytostatics may lead to leukopenia.

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

In contrast to other DMARDs, no clinically significant interaction of amlodipine has been found with NSAIDs, including indomethacin.

The antianginal and hypotensive effect of PBMCs may be enhanced when used with thiazide and loop diuretics, ACE inhibitors and nitrates and their antihypertensive effect may be increased when used simultaneously with alpha1-adrenoblockers.

Eritromycin when used together increases Cmax of amlodipine by 22% in young patients and by 50% in elderly patients.

Beta-adrenoblockers combined with amlodipine may cause exacerbation of chronic heart failure.

While no negative inotropic effects have generally been observed with amlodipine, some DMARDs can exacerbate the negative inotropic effects of antiarrhythmic agents that cause QT interval prolongation (e.g., amiodarone and quinidine).

A single use of sildenafil 100 mg in patients with arterial hypertension has no effect on pharmacokinetic parameters of amlodipine.
Reuse of amlodipine 10 mg and atorvastatin 80 mg does not cause significant changes in pharmacokinetic parameters of atorvastatin.

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

Antiretroviral agents (ritonavir) increase plasma concentrations of PBMCs, including amlodipine.
Neuroleptics and isoflurane increase the hypotensive effect of dihydropyridine derivatives.
Calcium preparations may decrease the effect of PBMCs.

The co-administration of amlodipine with lithium preparations may increase neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not alter the pharmacokinetics of cyclosporine.

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

There is 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 the binding to plasma proteins, digoxin, phenytoin, warfarin and indomethacin.

Grapefruit juice: Concomitant administration of 240 mg of grapefruit juice and 10 mg of oral amlodipine is not accompanied by significant changes in pharmacokinetics of amlodipine.

Aluminum- or magnesium-containing antacids: their single administration has no significant effect on amlodipine pharmacokinetics.

Special Instructions

The treatment with the drug Equacard can be started only after correction of hyponatremia and restoration of circulating blood volume.

After taking the first dose of the drug, close control of BP is recommended, a significant decrease in BP with the development of symptomatic arterial hypotension is possible. Significant BP decrease occurs most often in case of BAC decrease caused by diuretic therapy, reduction of table salt content in food, dialysis, diarrhea or vomiting.
In case of arterial hypotension the patient should be placed horizontally and if necessary, a solution to compensate the volume of circulating fluid (infusion of 0.9% sodium chloride solution) should be infused intravenously.

The same rules should be followed when using the drug Equacard in patients with CHD, cerebrovascular insufficiency, in whom a sharp decrease in BP may lead to myocardial infarction or stroke.

In case of aortic stenosis, hypertrophic obstructive cardiomyopathy the administration of vasodilator requires caution.
During therapy with Equacard® it is necessary to control body weight and table salt intake and administration of appropriate diet is indicated.

Maintain oral hygiene and see a dentist (to prevent soreness, bleeding and gum hyperplasia).

Peripheral blood should be monitored periodically during therapy, since the potential risk of agranulocytosis cannot be excluded, periodic peripheral blood monitoring is required.

In impaired renal function, such as renal artery stenosis (especially bilateral or arterial stenosis of the sole kidney), hyponatremia, dehydration, circulatory insufficiency, administration of the drug may provoke renal function impairment and acute renal failure reversible after stopping treatment. Patients with impaired renal function should be monitored.

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

In patients with impaired hepatic function the half-life of amlodipine is prolonged; in these patients the drug is indicated with caution after benefit and risk assessment. When using ACE inhibitors, angioedema of face, limbs, lips, tongue, epiglottis or larynx may develop, requiring immediate discontinuation of treatment with the drug and establishment of medical supervision until symptoms completely regress. Angioedema with laryngeal edema can be fatal. Swelling of the tongue, epiglottis or pharynx may cause airway obstruction, so appropriate therapy (0.3-0.5 ml 1:1000 solution of epinephrine (adrenaline) p/k) and/or airway management should be initiated immediately. In cases where the swelling is localized only to the face and lips, the condition usually resolves without treatment, but antihistamines may be used.

The risk of angioedema is increased in patients who have a history of angioedema from ACE inhibitors.

Patients taking ACE inhibitors during a desensitization procedure to hymenopteran venom may very rarely develop life-threatening anaphylactoid reactions. This can be avoided by temporarily discontinuing ACE inhibitor treatment before each hymenoptera desensitization procedure.

Surgery/general anesthesia: When using general anesthesia agents with antihypertensive effects and when performing extensive surgical procedures, lisinopril inhibits angiotensin-II formation in response to compensatory renin release. In such arterial hypotension, BP is normalized by increasing circulating blood volume.

The surgeon/anesthesiologist should be informed about the use of an ACE inhibitor before surgical procedures (including dental surgery).

Anaphylactoid reactions have also been reported in patients on hemodialysis using high flow dialysis membranes (AN69) who are simultaneously taking ACE inhibitors. In such cases, another type of dialysis membrane or another hypotensive agent should be considered. When selecting a dose, it should be taken into account that in elderly patients both active ingredients are detected in the blood at higher concentrations, with no change in efficacy.

Cough has been noted with ACE inhibitors. The cough is dry and prolonged, which disappears after discontinuation of ACE inhibitor treatment. In the differential diagnosis of cough, cough caused by ACE inhibitor use must also be considered.

Contraindications

Side effects

The incidence of adverse reactions below was determined according to the following (World Health Organization classification): very common – at least 10%; common – at least 1%, but less than 10%; infrequent – at least 0.1%, but less than 1%; rare – at least 0.01%, but less than 0.1%; very rare – less than 0.01%, including individual reports.

Lisinopril

Cardiovascular system disorders: frequent – marked BP decrease, orthostatic hypotension; infrequent – acute myocardial infarction, tachycardia, palpitations; Raynaud’s syndrome; rare – bradycardia, tachycardia, aggravation of symptoms of the course of chronic heart failure, atrioventricular conduction disorder, chest pain.

CNS disorders: frequently – dizziness, headache; infrequently – mood swings, paresthesia, sleep disturbances, stroke; rarely – mental confusion, asthenic syndrome, convulsive twitching of limbs and lips, somnolence.

Hematopoietic system and lymphatic system: rarely – decrease of hemoglobin, hematocrit; very rarely – leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, erythropenia, hemolytic anemia, lymphadenopathy, autoimmune diseases.

Respiratory system: frequently – cough; infrequently – rhinitis; very rarely – sinusitis, bronchospasm, allergic alveolitis/eosinophilic pneumonia, dyspnea.

The digestive system: frequently – diarrhea, vomiting; infrequently – dyspepsia, changes in taste, abdominal pain; rarely – dry oral mucosa; very rarely – pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis, liver failure, interstitial edema, anorexia.

Skin disorders: infrequent – skin itching, rash; rarely – angioedema of the face, extremities, lips, tongue, throat, urticaria, alopecia, psoriasis; very rarely – excessive sweating, vasculitis, vesicular rash, photosensitization, toxic epidermal necrolysis (Lyell syndrome), erythema multiforme, Stevens-Johnson syndrome.

Urinary system disorders: common – renal dysfunction; infrequent – uremia, acute renal failure; very rarely – anuria, oliguria, proteinuria.

With the reproductive system: infrequent impotence, rarely – gynecomastia.

Metabolism: very rare – hypoglycemia.

Laboratory disorders: infrequent – increased blood urea concentration, hypercreatininemia, hyperkalemia, increased liver transaminase activity, rare – hyperbilirubinemia, hyponatremia, increased erythrocyte sedimentation rate, false positive results of antinuclear antibodies test.

Musculoskeletal system: rarely – arthralgia/arthritis, myalgia.

Amlodipine

CNS side: frequent – headache (especially at the beginning of treatment), dizziness, increased fatigue, sniffling; infrequent – general malaise, hypoesthesia, 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.

Digestive system disorders: frequent – nausea, abdominal pain; infrequent – vomiting, change of defecation mode (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry oral mucosa, thirst; rare – gum hyperplasia, increased appetite; very rare – pancreatitis, gastritis, jaundice (usually cholestatic), hyperbilirubinemia, increased activity of “liver” transaminases, hepatitis.

Cardiovascular system disorders: frequent – peripheral edema (ankles and feet), palpitations, “rushes” of blood to the skin of the face; infrequent – excessive reduction of BP, orthostatic hypotension, vasculitis; rare – development or aggravation of the course of chronic heart failure; Very rare – syncope, dyspnea, cardiac rhythm disorders (including bradycardia, ventricular tachycardia, and atrial fibrillation), myocardial infarction, chest pain, pulmonary edema, migraine.

Hematopoietic and lymphatic system disorders: very rarely – thrombocytopenic purpura, leukopenia, thrombocytopenia.

The urinary system: infrequent – pollakiuria, painful urge to urinate, nycturia; very rare – dysuria, polyuria.

Reproductive system and mammary glands: infrequent – gynecomastia, impotence.

Respiratory system disorders: infrequent dyspnea, rhinitis; very rare – cough.

Musculoskeletal system: infrequent muscle cramps, myalgia, arthralgia, back pain, arthrosis; rarely – myasthenia.

The skin: infrequent alopecia: rare – dermatitis; very rare – alopecia, xeroderma, cold clammy sweat, impaired skin pigmentation.

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

Sensory system disorders: infrequent – tinnitus, visual disturbances, diplopia, accommodation disorders, xerophthalmia, conjunctivitis, eye pain; very rare – parosmia.

Metabolism disorders: very rarely – hyperglycemia.

Others: infrequent – weight loss, weight gain, perversion of taste, nasal bleeding, chills.

Overdose

Lisinopril

Symptoms: marked BP decrease, dry mouth, water-electrolyte imbalance, renal failure, rapid breathing, tachycardia, palpitations, bradycardia, dizziness, anxiety, increased irritability, cough, drowsiness, urinary retention, constipation.

Treatment: there is no specific antidote. Gastric lavage, enterosorbents and laxatives. IV administration of 0.9% sodium chloride solution is indicated. In the case of treatment-resistant bradycardia, it is necessary to use an artificial pacemaker. Necessary control of BP, water-electrolyte balance indicators. Hemodialysis is effective.

Amlodipine
Symptoms: significant BP decrease with possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including development of shock and death).

The treatment: gastric lavage, usage of activated charcoal (especially in the first 2 hours after overdose), maintenance of cardiovascular system function, elevated position of the lower extremities, monitoring of heart and lung function parameters, control of circulating blood volume (CBV) and diuresis.

In order to restore vascular tone we use vasoconstrictors (if there are no contraindications for their use); to eliminate the consequences of calcium channel blockade we inject calcium gluconate by IV. Hemodialysis is not effective.

Pregnancy use

The use of the drug Equacard is not recommended during pregnancy.

If pregnancy is diagnosed, the use of Equacard should be stopped as soon as possible.

The use of ACE inhibitors in the second and third trimester of pregnancy has adverse effects on the fetus (marked BP decrease, renal failure, hyperkalemia, skull bone hypoplasia, fetal death are possible). There are no data on the negative effects of the drug on the fetus if used during the first trimester. Newborns and infants who have been intrauterine exposed to ACE inhibitors are recommended to be closely monitored for timely detection of marked BP decrease, oliguria, hyperkalemia.

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

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

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

Yet other DMARDs, dihydropyridine derivatives, are known to be excreted in breast milk.

The use of Equacard® during breastfeeding is not recommended.

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

Similarities