Equapress, 5 mg+1.5 mg+20 mg capsules 28 pcs
€30.83 €25.69
Equapress is a fixed combination of the antihypertensive components amlodipine, indapamide and lisinopril, which have complementary mechanisms of action to control blood pressure (BP) and also have a synergistic cardioprotective effect.
The combination of amlodipine, indapamide and lisinopril prevents possible side effects of the individual components of the drug.
For example, by dilating the arterioles, slow calcium channel blockers (SCBs) can cause sodium and fluid retention in the body, which leads to activation of the renin-angiotensin-aldosterone system (RAAS).
The angiotensin-converting enzyme (ACE) inhibitor blocks this process and normalizes the body’s response to salt load.
The ACE inhibitors significantly reduce hypokalemia caused by diuretics.
Amlodipine
The dihydropyridine derivative is a “slow” calcium channel blocker that has antihypertensive and antianginal effects. It blocks “slow” calcium channels, decreases transmembrane transition of calcium ions into cells (more in vascular smooth muscle cells than in cardiomyocytes). 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 the peripheral arterioles, it reduces total peripheral vascular resistance, reduces the afterload on the heart, and reduces myocardial oxygen demand;
– expanding 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 spasm of coronary arteries (including those caused by smoking).Also caused by smoking.)
In patients with stable angina, a single daily dose increases exercise tolerance, delays the development of angina attacks and ST-segment depression by 1 mm, reduces the frequency of angina attacks and the 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 the vascular smooth muscles. In arterial hypertension a single dose provides clinically significant reduction of BP during 24 hours (in “lying” and “standing” positions).
Orthostatic hypotension when using amlodipine is quite rare.
Amlodipine does not decrease exercise tolerance and left ventricular ejection fraction.
It reduces the degree of left ventricular myocardial hypertrophy.
It does not influence myocardial contractility and conduction, does not cause reflex increase of heart rate, inhibits platelet aggregation, increases glomerular filtration rate, has weak natriuretic action.
In diabetic nephropathy it does not increase microalbuminuria. It does not have any adverse effect on metabolism and concentration of blood plasma lipids and can be used for therapy of patients with bronchial asthma, diabetes and gout.
The significant decrease of BP is observed after 6-10 hours, the duration of effect – 24 hours.
In patients with diseases of the cardiovascular system (including coronary atherosclerosis with lesions of one vessel and up to stenosis of 3 or more arteries, atherosclerosis of the carotid arteries) who had myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or in patients with angina pectoris, use of amlodipine prevents the development of carotid intima-media thickening and reduces mortality from myocardial infarction, stroke, PTCA, aortocoronary bypass;
Results in fewer hospitalizations for unstable angina and progression of chronic heart failure (CHF); reduces the frequency of interventions to restore coronary blood flow.
Does not increase risk of death or complications and lethal outcomes in patients with CHF (New York Heart Association (NYHA) functional class III-IV) during therapy with digoxin, diuretics and ACE inhibitors.
In patients with CHF (functional class III-IV according to NYHA classification) of non-ischemic etiology, the use of amlodipine may cause pulmonary edema.
Indapamide
Indapamide refers to sulfonamide derivatives with an indole ring and has pharmacological properties similar to thiazide diuretics, which inhibit sodium ion absorption in the cortical segment of the nephron loop.
The renal excretion of sodium and chlorine ions and, to a lesser extent, potassium and magnesium ions is increased, which is accompanied by increased diuresis and antihypertensive effect.
In clinical studies, a 24-hour antihypertensive effect has been demonstrated with indapamide in monotherapy in doses without a pronounced diuretic effect.
The antihypertensive activity of indapamide is associated with improvement of elastic properties of large arteries, reduction of arteriolar and total peripheral vascular resistance.
Indapamide reduces left ventricular hypertrophy.
The thiazide and thiazide-like diuretics reach a plateau of therapeutic effect at a certain dose, while the incidence of side effects continues to increase with further increases in the dose of the drug.
Hence, the dose of the drug should not be increased if the therapeutic effect has not been achieved at the recommended dose.
In short-, medium-, and long-term studies involving patients with arterial hypertension, it has been shown that indapamide:
– has no effect on lipid metabolism, including triglyceride, cholesterol, low and high density lipoprotein concentrations;
– has no effect on carbohydrate metabolism, including in patients with diabetes.
Lisinopril
Lisinopril is an ACE inhibitor and inhibits the transformation of angiotensin I into angiotensin II. Reducing the concentration of angiotensin II leads to a direct reduction of aldosterone secretion.
Lisinopril suppresses bradykinin degradation and increases prostaglandin synthesis. It reduces total peripheral vascular resistance, BP, preload and pulmonary capillary pressure. In patients with CHF it increases minute blood volume and increases myocardial resistance to stress.
Dilates arteries more than veins. Some effects are explained by its effect on the tissue renin-angiotensin system. Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy.
Lisinopril improves the blood supply to the ischemic myocardium.
In patients with CHF, ACE inhibitors increase life expectancy; in patients with a history of myocardial infarction in the absence of clinical manifestations of heart failure, lisinopril slows the progression of left ventricular dysfunction.
In patients with CHF, lisinopril begins to take effect within 1 hour after oral administration.
Maximal effect is reached within 6-7 hours; effect duration is 24 hours.
In patients with arterial hypertension the effect is seen during the first days after the start of treatment; the stabilization of the effect occurs within 1-2 months of treatment. There have been no registered cases of marked increase in BP after abrupt withdrawal of the drug.
Lisinopril provides both BP reduction and albuminuria reduction.
In patients with hyperglycemia the drug promotes restoration of function of damaged glomerular endothelium. In patients with diabetes, lisinopril has no effect on plasma glucose concentration; the drug does not lead to increased incidence of hypoglycemia.
Indications
Arterial hypertension (patients who require combination therapy).
Active ingredient
Amlodipine, Indapamide, Lisinopril
Composition
Active ingredients:
Amlodipine besylate – 6.934 mg (equivalent to amlodipine 5 mg),
indapamide – 1.5 mg,
lisinopril dihydrate – 21.776 mg (equivalent to lisinopril 20 mg).
Auxiliary substances:
Lactose monohydrate,
hypromellose,
calcium hydrophosphate dihydrate,
mannitol,
corn starch,
microcrystalline cellulose,
croscarmellose sodium,
talc,
p> magnesium stearate,
colloidal silicon dioxide,
Opadray II white (contains: polyvinyl alcohol, titanium dioxide, macrogol-3350, talc),
solid gelatin capsule (contains: iron oxide yellow dye, iron oxide red dye, water, gelatin).
How to take, the dosage
Instructions for Use
The drug Equapress is taken orally, regardless of meals.
Doses
The fixed-dose combination medication is not recommended for initial therapy.
Prevapress is indicated in adult patients who have achieved adequate BP control while taking lisinopril, amlodipine and indapamide, which the patient takes simultaneously in the same doses as the combination drug:
Amlodipine 5 mg, indapamide 1.5 mg, lisinopril 10 mg (Equapress 5 mg + 1.5 mg + 10 mg), amlodipine 10 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 10 mg + 1.5 mg + 20 mg), amlodipine 5 mg, indapamide 1.5 mg, lisinopril 20 mg (Equapress 5 mg + 1.5 mg + 20 mg).
The recommended dose is 1 capsule daily, preferably in the morning, at the same time each day. The maximum daily dose is 1 capsule.
If symptomatic arterial hypotension develops at the beginning of treatment with Equapress, the patient should lie on his back, suspend the drug and consult a physician. Transient arterial hypotension usually does not require withdrawal of the drug, but the need for dose reduction should be assessed.
If a dose adjustment is necessary, amlodipine, indapamide and lisinopril should be used separately.
Missing a dose
If you forget to take a capsule of Equapress, take the next dose at the usual time. Do not take two capsules at the same time to make up for a missed dose.
Patient special groups
Patients with renal impairment
With Equapress therapy, renal function and serum potassium and sodium should be monitored. If renal function is impaired, Equapress should be discontinued and replaced with an individually tailored single component therapy.
Patients with hepatic impairment
In patients with impaired hepatic function, amlodipine excretion may be delayed. There are no precise recommendations for these cases, so Equapress should be used with caution in these patients.
Children and adolescents (< 18 years)
The safety and effectiveness of Equapress in children and adolescents has not been established.
Elderly patients (>65 years)
This drug should be used with caution in elderly patients.
Plasma creatinine concentrations should be monitored according to age, body weight, and sex.
There have been no age-related changes in the efficacy and safety profile of amlodipine or lisinopril in clinical studies.
Interaction
Amlodipine
Contraindicated drug combinations
Dantrolene (intravenous administration)
There have been cases of fatal ventricular fibrillation and collapse in laboratory animals when using verapamil and intravenous administration of dantrolene. accompanied by hyperkalemia.
Due to risk of hyperkalemia concomitant use of Equapress containing amlodipine, slow calcium channel blocker, should be excluded in patients with malignant hyperthermia and during treatment of malignant hyperthermia.
Unrecommended drug combinations
Grapefruit juice
Taking amlodipine with grapefruit or grapefruit juice is not recommended because in some patients the bioavailability of amlodipine may increase, resulting in increased BP-lowering effects.
Combinations of drugs requiring particular caution when using
CYP3A4 isoenzyme inducers
There are no data on the effect of CYP3A4 isoenzyme inducers on amlodipine pharmacokinetics. Concomitant use of CYP3A4 isoenzyme inducers (e.g., rifampicin, St. John’s Wort preparations) and amlodipine may lead to decreased plasma concentration of amlodipine.
Caution should be exercised when using Equapress concomitantly with CYP3A4 isoenzyme inducers.
CYP3A4 isoenzyme inhibitors
. Simultaneous use of amlodipine and strong or moderate CYP3A4 inhibitors (protease inhibitors, e.g. ritonavir, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may cause significant increase in amlodipine concentration.
Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, it may be necessary to monitor the clinical condition and adjust the dose of the drug Equipress.
Drug combinations requiring caution when using
Simvastatin
Multiple administration of amlodipine at a dose of 10 mg in combination with simvastatin at a dose of 80 mg resulted in an increase in simvastatin exposure of 77% compared to simvastatin monotherapy. Thus, patients receiving amlodipine should take simvastatin in a daily dose not exceeding 20 mg.
Calcium preparations
May decrease the effect of DMARDs.
Lithium preparations
The co-administration of BMCC with lithium preparations (no data for amlodipine) may increase their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor or tinnitus).
Baclofen
Augmentation of the antihypertensive effect. BP and renal function should be monitored; if necessary, the dose of amlodipine should be adjusted.
Amifostine
Amifostine may increase the antihypertensive effect of amlodipine.
Glucocorticosteroids
Decreased antihypertensive effect (fluid and sodium ion retention as a result of corticosteroid action).
Tricyclic antidepressants neuroleptics, isoflurane
There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).
Tacrolimus
In concomitant use with amlodipine there is a risk of increased plasma concentrations of tacrolimus.
To avoid tacrolimus toxicity when used concomitantly with amlodipine, patients’ plasma tacrolimus concentrations should be monitored and the tacrolimus dose adjusted if necessary.
Tasonermin
Concomitant use of amlodipine may increase the systemic plasma exposure of tasonermin. In such cases, regular monitoring of tasonermine in blood and dose adjustment if necessary are required.
Other interactions with amlodipine
Amlodipine may be safely used with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers and ACE inhibitors for treatment of arterial hypertension.
In patients with stable angina pectoris simultaneous use of amlodipine with other antianginal drugs, such as long- and short-acting nitrates, beta-adrenoblockers is possible.
The antianginal and antihypertensive effects of DMARDs are likely to be enhanced with thiazide and loop diuretics, ACE inhibitors, beta-adrenoblockers and nitrates and their antihypertensive effects are likely to be enhanced when prescribed with alpha 1-adrenoblockers and neuroleptics.
Amlodipine does not cause negative inotropic effects. However, some BMCCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (e.g., amiodarone and quinidine).
Unlike other PBMC, no significant interaction of amlodipine (3rd generation PBMC) and NSAIDs, including indomethacin, was found.
It is safe to prescribe amlodipine with oral hypoglycemic drugs. A single sildenafil administration at a dose of 100 mg in patients with essential arterial hypertension had no effect on amlodipine pharmacokinetics.
Co-administration of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg resulted in insignificant changes in pharmacokinetic parameters of atorvastatin at equilibrium concentration state.
Ethanol (beverages containing alcohol): amlodipine has no significant effect on the pharmacokinetics of ethanol with single and multiple doses of 10 mg. Studies of interaction between cyclosporine and amlodipine in healthy volunteers and in special patient groups have not been conducted, except for patients after kidney transplantation.
Various studies of interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may either lead to no effect, or increase the minimum concentration of cyclosporine to varying degrees up to 40%. Cyclosporine concentrations should be monitored in patients after kidney transplantation.
When concomitant use of amlodipine and digoxin, renal clearance and serum concentrations of digoxin are not changed.
Concomitant use of warfarin with amlodipine does not change prothrombin time.
The pharmacokinetics of amlodipine is not changed when concomitant use with cimetidine.
Amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin and indomethacin to plasma proteins in vitro.
Aluminum and magnesium-containing antacids: single administration of these antacids together with amlodipine has no significant effect on the pharmacokinetics of amlodipine.
Indapamide
Controlled combinations of drugs
Lithium preparations
When indapamide and lithium preparations are used concomitantly, as well as when adhering to a salt-free diet, increased plasma lithium concentrations may occur due to decreased excretion, accompanied by signs of overdose.
If necessary, diuretics may be used in combination with lithium preparations, and plasma lithium concentration should be carefully monitored and the dose of the drug should be adjusted accordingly.
Combinations of drugs that require special caution during use
Drugs that can cause polymorphic ventricular tachycardia such as “pirouette”
– Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide).
– Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide).
– Certain neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, thiapride), butyrophenones (droperidol, haloperidol).
– Others: bepridil, cisapride, difemanil, erythromycin (intravenous), halofantrine, misolastin, pentamidine, sparfloxacin, moxifloxacin, astemizole, vincamine (intravenous).
Increased risk of ventricular arrhythmias, especially pirouette-type polymorphic ventricular tachycardia (hypokalemia is a risk factor).
In patients with hypokalemia, drugs that do not cause pirouette-type polymorphic ventricular tachycardia should be used.
Non-steroidal anti-inflammatory drugs (when used systemically), including selective COX-2 inhibitors, high doses of salicylic acid (≥3 g/day)
The antihypertensive effect of indapamide may decrease.
There is a risk of acute renal failure due to decreased glomerular filtration. Patients should compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
ACE inhibitors
The administration of ACE inhibitors to patients with initially decreased concentration of sodium ions in blood (especially patients with renal artery stenosis) is accompanied by the risk of sudden arterial hypotension and/or acute renal failure.
Patients with arterial hypertension and possibly decreased content of sodium ions in blood plasma due to taking diuretics should:
– 3 days before starting treatment with ACE inhibitor stop taking diuretic. Subsequently, if necessary, the intake of noncaliberative diuretic may be resumed;
– or therapy with ACE inhibitor may be started at low doses with subsequent gradual increase of the dose if necessary.
In chronic heart failure, treatment with ACE inhibitors should be started at the lowest dose with possible prior reduction in doses of diuretics. In all cases during the first weeks of taking ACE inhibitors in patients it is necessary to monitor renal function (creatinine content in plasma).
Other drugs that may cause hypokalemia: amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when used systemically), tetracosactide, intestinal motility stimulating laxatives
Additive effect increases risk of hypokalemia.
Potassium concentration in plasma should be monitored constantly, and corrected if necessary. Particular attention should be paid to patients concomitantly receiving cardiac glycosides.
The use of laxatives that do not stimulate intestinal motility is recommended.
Baclofen
Augmentation of the antihypertensive effect has been noted.
Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.
Cardiac glycosides
Hypokalemia increases the toxic effects of cardiac glycosides.
In concomitant use of indapamide and cardiac glycosides, plasma potassium and ECG parameters should be monitored and, if necessary, therapy should be adjusted.
Combinations of drugs requiring caution when using
Potassium-saving diuretics (amiloride, spironolactone, triamterene, eplerenone) Combination therapy with indapamide and potassium-saving diuretics is reasonable in some patients, but cannot exclude the possibility of hypokalemia or hyperkalemia (especially in diabetic patients or patients with renal impairment).
Potassium concentration in plasma and ECG parameters should be monitored and, if necessary, therapy should be adjusted.
Metformin
Functional renal insufficiency, which may occur with diuretics, especially loop diuretics, when metformin is concomitantly administered increases the risk of lactic acidosis.
Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.
Iodine-containing contrast agents
In dehydration caused by diuretics, the risk of acute renal failure increases, especially when using high doses of iodine-containing contrast agents.
Patients should compensate for fluid loss before using iodine-containing contrast agents.
Tricyclic antidepressants, antipsychotics (neuroleptics)
The drugs of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).
Calcium salts
Concomitant use increases the risk of hypercalcemia due to reduced renal excretion of calcium ions.
Cyclosporine, tacrolimus
Possible increase in plasma creatinine without change in circulating cyclosporine concentration, even with normal circulating blood volume and plasma sodium content.
Glucocorticosteroid drugs, tetracosactide (when used systemically)
Decrease antihypertensive effect (fluid and sodium ion retention caused by corticosteroids).
Lisinopril
Contraindicated drug combinations
Aliskiren
Concomitant use of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and/or moderate to severe renal function impairment (GFR less than 60 ml/min/1.73 m2 body surface area) is contraindicated.
The administration of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy.
Unrecommended drug combinations
Angiotensin II receptor antagonists (ARA II)
. In patients with established atherosclerotic disease, chronic heart failure, or diabetes mellitus with target organ damage, concurrent therapy with an ACE inhibitor and ARA II has been reported in the literature to be associated with higher rates of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to use of the RAAS-acting drug alone.
Double blockade (e.g., when ACE inhibitor is combined with ARA II) should be limited to individual cases with close monitoring of renal function, potassium and BP.
Potassium preparations, potassium-saving diuretics (spironolactone, triamterene, amiloride. eplerenone) or potassium-containing salt substitutes
Possible hyperkalemia (possibly fatal), especially with impaired renal function (additional effects associated with hyperkalemia).
The ACE inhibitors should not be used concomitantly with substances that increase plasma potassium levels, except in cases of hypokalemia.
The combination of lisinopril and the above agents is not recommended. Nevertheless, if concomitant use is indicated, they should be used with caution and serum potassium levels should be monitored regularly.
Lithium preparations
Simultaneous use of lithium preparations and ACE inhibitors may cause reversible increase in serum lithium concentration and associated toxic effects.
The concomitant use of lisinopril and lithium preparations is not recommended. Serum lithium concentrations should be monitored regularly if such therapy is necessary.
Combinations of drugs that require special caution when using
Insulin and oral hypoglycemic agents
Isulin and oral hypoglycemic agents Epidemiologic studies have shown that coadministration of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) can increase their hypoglycemic effects to the point of hypoglycemia.
This effect is most likely to be observed during the first weeks of concomitant therapy, as well as in patients with impaired renal function. Baclofen
Enhances the antihypertensive effect of ACE inhibitors. BP should be carefully monitored and, if necessary, the dose of hypotensive drugs should be adjusted.
Diuretics
In patients taking diuretics, especially fluid- and/or salt-removing diuretics, a significant decrease in BP may be observed at the beginning of ACE inhibitor therapy.
The risk of antihypertensive effects can be reduced by withdrawing the diuretic, replenishing fluid or salt loss before starting therapy with ACE inhibitors.
In patients with arterial hypertension with prior diuretic therapy that may have resulted in excess fluid and/or salt excretion, diuretics should be discontinued prior to initiation of Equapress.
Renal function (creatinine concentration) should be monitored during the first weeks of use of Equapress.
Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥3 g/day. Concomitant use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose with anti-inflammatory effect, cyclooxygenase-2 inhibitors (COX-2) and non-selective NSAIDs) may lead to a decrease in the antihypertensive effect of ACE inhibitors.
Concomitant use of ACE inhibitors and NSAIDs may lead to worsening of renal function, including the development of acute renal failure and increased serum potassium, especially in patients with reduced renal function.
Caution should be exercised when prescribing this combination, especially in elderly patients. Patients should compensate for fluid loss and carefully monitor renal function both at the beginning of treatment and during treatment.
Estramustine, mTOR inhibitors (sirolimus, everolimus, temsirolimus), neutral endopeptidase inhibitors (omapatrilat, ilepatril, daglutril, sacubitril) Simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of angioedema.
DPP-4 inhibitors (glyptins)
Linagliptin, saxagliptin, sitagliptin, vildagliptin – when combined with ACE inhibitors, there is an increased risk of angioedema due to inhibition of dipeptidyl peptidase-4 (DPP-4 ) activity by glyptin.
Racecadotril (enkephalinase inhibitor used for the treatment of acute diarrhea)
The risk of angioedema may increase when used concomitantly with ACE inhibitors.
Combinations of drugs requiring caution when using
Other antihypertensive agents (e.g., beta-adreno-blockers, slow calcium channel blockers, diuretics) and vasodilators
An increase in the antihypertensive effect of the drug is possible. Caution should be exercised when concomitant administration with nitroglycerin, other nitrates, or other vasodilators because additional BP reduction is possible.
Antacids and cholestyramine
The concomitant use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.
Tricyclic antidepressants, neuroleptics, general anesthetics, barbiturates, phenothiazine, ethanol
The effect of lisinopril may be enhanced when taken together.
Sympathomimetics
Sympathomimetics may decrease the antihypertensive effect of ACE inhibitors.
Myorelaxants
The concomitant use of muscle relaxants with ACE inhibitors may result in a marked decrease in blood pressure.
Gold preparations
In the use of ACE inhibitors, including lisinopril, by patients receiving intravenous gold preparations (sodium aurothiomalate), rare cases of nitrite reactions (symptomcomplex including facial hyperemia, nausea, vomiting and arterial hypotension) have been described.
Co-trimoxazole (sulfamethoxazole and trimethoprim)
An increased risk of hyperkalemia.
Selective serotonin reuptake inhibitors (SSRIs: escitalopram, paroxetine, fluoxetine, sertraline)
The simultaneous use with SSRIs may result in significant hyponatremia.
Allopurinol, procainamide, cytostatics (5-fluorouracil, vincristine, docetaxel)
Leukopenia may occur.
Tissue plasminogen activators (alteplase, reteplase, tenecteplase)
Increased risk of angioedema when combined with ACE inhibitors.
Special Instructions
If you are hospitalized, tell your physician that you are taking Equapress.
When using Equapress, please note the special instructions regarding the individual components of the drug.
Amlodipine-related
Tooth hygiene must be maintained and monitored by a dentist (to prevent soreness, bleeding, and gum hyperplasia).
In elderly patients, the T1/2 may increase and the clearance of amlodipine may decrease. No change in doses is required, but closer monitoring of patients in this category is necessary.
The efficacy and safety of amlodipine in hypertensive crisis have not been established.
In in vitro studies it has been shown that amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin or indomethacin to human plasma proteins.
While there is no withdrawal syndrome in BMKK, it is advisable to discontinue amlodipine treatment by gradually reducing the dose of the drug.
An increased incidence of pulmonary edema has been observed with amlodipine in patients with CHF class III and IV according to NYHA nonischemic genesis, despite the absence of signs of worsening heart failure.
The effect on fertility
In some patients receiving calcium channel blockers, reversible biochemical changes in the sperm head have been found, which may be clinically significant in in vitro fertilization (IVF).
There are, however, currently insufficient clinical data regarding the potential effect of amlodipine on fertility. In a preclinical study, adverse effects on fertility were found in males.
Indapamide-related
Hepatic impairment
Patients with hepatic impairment may develop hepatic encephalopathy when prescribing thiazide and thiazide-like diuretics, especially in the presence of electrolyte imbalance. In this case it is necessary to stop using diuretics.
Photosensitization
Photosensitization cases have been reported with thiazide and thiazide-like diuretics. If photosensitization occurs, withdrawal of these drugs is indicated. If it is necessary to continue treatment, protection of the skin from sunlight or artificial UV radiation is recommended.
Phyto-electrolyte balance
Phyto-electrolyte balance
Phyto-electrolyte balance should be determined and regularly monitored before starting treatment. All diuretics can cause hyponatremia, which can have very serious consequences.
Permanent monitoring of plasma sodium is necessary, since at first sodium reduction may have no clinical manifestations. Sodium should be especially carefully monitored in patients with cirrhosis and in the elderly.
All diuretics can cause hyponatremia, sometimes leading to extremely serious consequences. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension.
The concomitant reduction of chlorine ions may lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect is negligible.
Plasma potassium content
Per therapy with thiazide and thiazide-like diuretics may cause significant decrease of plasma potassium content and development of hypokalemia.
The risk of hypokalemia (< 3.4 mmol/l) should be prevented in the following groups of patients: elderly, frail patients and/or those receiving combined drug therapy, patients with liver cirrhosis, peripheral edema and ascites, coronary heart disease, heart failure.
In these patients, hypokalemia increases the toxic effects of cardiac glycosides and increases the risk of arrhythmias. In addition, patients with a prolonged QT interval are at high risk, regardless of whether this prolongation is caused by congenital causes or by medications.
Hypokalemia, like bradycardia, contributes to severe arrhythmias, especially cardiac arrhythmias that can be fatal. The first measurement of plasma potassium should be made within the first week of starting treatment. If hypokalemia is detected, appropriate therapy is indicated.
Thiazide and thiazide-like diuretics decrease urinary calcium excretion, which leads to a slight temporary increase in plasma calcium content. Hypercalcemia with clinical manifestations may be the result of previously undiagnosed hyperparathyroidism.
Diuretics should be discontinued until parathyroid function is investigated.
Plasma glucose
Control of glucose concentration in patients with diabetes mellitus is indicated, especially in the presence of hypokalemia.
Uracilic acid
In gout sufferers, an increase in the frequency of gout attacks or exacerbation of gout is possible.
Diuretics and renal function
Thiazide and thiazide-like diuretics are most effective in patients with normal or slightly reduced renal function (adult plasma creatinine < 25 mg/l or 220 μmol/l). Plasma creatinine concentrations in elderly patients are evaluated according to age, body weight and sex.
In the beginning of treatment, patients may have decreased glomerular filtration rate due to hypovolemia, which may be associated with water and sodium loss due to diuretics.
The increase in plasma concentrations of uric acid and creatinine may be associated with this. When renal function is preserved, such transient functional renal failure usually goes without complications.
However, in the presence of renal insufficiency, the general condition of patients may worsen.
Athletes
Indapamide may give a positive doping control result in athletes.
Lisinopril-related
Symptomatic arterial hypotension
The most common reason for a pronounced decrease in BP is hypovolemia caused by diuretics, decreased salt in food, dialysis, diarrhea, or vomiting. In patients with CHF, regardless of whether it is associated with renal failure, arterial hypotension may develop.
It has been found that in patients with severe heart failure this condition occurs more frequently due to administration of high doses of diuretics, hyponatremia or impaired renal function.
In these patients careful medical monitoring is required (doses of lisinopril and diuretics should be carefully selected). The same instructions apply to patients with coronary heart disease and cerebrovascular insufficiency, in whom a sharp decrease of BP may lead to myocardial infarction or stroke.
If the patient’s blood pressure decreases significantly, it is recommended that the patient be placed in a supine position; if necessary, 0.9% sodium chloride solution should be administered intravenously.
A transient hypotensive reaction is not a contraindication for taking the next dose of lisinopril.
In patients with CHF but with normal or reduced BP, use of lisinopril may lead to a decrease in BP; this is not usually a reason to discontinue the drug.
If arterial hypotension progresses to symptomatic hypotension, reduction of the drug dose or discontinuation of treatment with the drug is necessary. In patients at risk of symptomatic arterial hypotension (with low-salt or no-salt diet), regardless of the presence of hyponatremia, as well as in patients receiving high-dose diuretics, it is necessary to compensate hypovolemia or sodium deficiency before the start of treatment.
The BP should be monitored when taking the first dose of lisinopril.
Acute myocardial infarction
Standard treatment (thrombolytics, acetylsalicylic acid, beta-adrenoblockers) is recommended. Lisinopril may be used concomitantly with intravenous nitroglycerin or transdermal nitroglycerin.
In patients with acute myocardial infarction and risk of further deterioration of hemodynamics, worsening of symptoms after prescribing vasodilators, therapy with lisinopril should not be started.
These are patients with systolic BP ≤100 mm Hg and patients with cardiogenic shock. In patients with systolic BP < 120 mm Hg during the first three days after myocardial infarction, dose reduction is indicated.
In patients with systolic BP ≤100 mm Hg, the maintenance dose should be reduced to 5 mg (or temporarily to 2.5 mg). In patients with persistent arterial hypotension (systolic BP < 90 mm Hg for 1 hour or more), discontinuation of lisinopril is indicated.
Renal dysfunction
In patients with CHF, a significant decrease in BP with ACE inhibitors may lead to increased renal dysfunction. Cases of acute renal failure have been reported.
In patients with bilateral renal artery stenosis or renal artery stenosis of the only kidney, elevated serum urea and creatinine concentrations have been noted with ACE inhibitors; usually these abnormalities were transient and ceased after therapy withdrawal. They were more common in patients with renal insufficiency.
In patients with acute myocardial infarction and severe renal dysfunction (serum creatinine concentration >177 μmol/l and/or proteinuria >500 mg/day) lisinopril should not be prescribed.
If renal function abnormalities develop during treatment (serum creatinine concentration >265 μmol/l or doubling of baseline), discontinuation of lisinopril is indicated.
Hypersensitivity, angioedema
In rare cases, the development of angioedema of the face, limbs, lips, tongue, epiglottis and/or larynx has been noted during use of ACE inhibitors, including lisinopril.
In such cases, immediate discontinuation of lisinopril is required; monitoring of patients until complete resolution of symptoms is indicated. Usually angioedema of the face and lips is temporary and does not require treatment; however, antihistamines may be prescribed.
Angioedema of the larynx can lead to death. Swelling of the tongue, epiglottis or larynx may lead to secondary airway obstruction. In this case, 0.3-0.5 ml of 1:1000 adrenaline solution should be administered immediately subcutaneously, and the airway should be secured.
In rare cases, against the background of ACE inhibitor therapy, angioedema of the intestine has developed. Patients have reported abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases without preceding angioedema of the face and with normal C1-esterase levels.
The diagnosis was established by abdominal computed tomography, ultrasonography, or surgery. Symptoms disappeared after discontinuation of ACE inhibitors.
Therefore, in patients with abdominal pain receiving ACE inhibitors, the possibility of angioedema of the bowel must be considered in the differential diagnosis.
In patients with a history of angioedema not associated with ACE inhibitor use, the risk is higher with ACE inhibitors.
Anaphylactic reactions required with Hymenoptera desensitization
In very rare cases, patients taking ACE inhibitors may develop life-threatening anaphylactic reactions during Hymenoptera desensitization, so ACE inhibitors must be temporarily withdrawn before desensitization.
Patients on hemodialysis
Anaphylactic reactions have also occurred in patients undergoing hemodialysis with high permeability dialysis membranes (e.g., AN69) who simultaneously received ACE inhibitors. Other dialysis membranes or other hypotensive medications are indicated in these patients.
Cough
Therapy with ACE inhibitors may cause cough, which should be considered in the differential diagnosis. Prolonged dry cough usually stops after discontinuation of ACE inhibitors.
Surgical interventions/general anesthesia
The use of hypotensive drugs during major surgery or during general anesthesia may result in inhibition of angiotensin II formation due to compensatory renin secretion.
The significant decrease in BP associated with this effect can be prevented by increasing circulating blood volume.
Patients taking ACE inhibitors should inform their surgeon/anesthesiologist prior to surgical procedures (including dental procedures).
Serum potassium
Cases of hyperkalemia have been reported.
Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, therapy with potassium-saving diuretics (spironolactone, triamterene and amiloride), use of potassium preparations and potassium-based salt substitutes, especially in patients with impaired renal function.
When combined use of lisinopril and these drugs is necessary, regular monitoring of serum potassium concentrations is indicated.
Double RAS blockade
The simultaneous use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of arterial hypotension, hyperkalemia, and renal function impairment (including acute renal failure).
Hence, combined administration of ACE inhibitors, angiotensin II receptor blockers or aliskiren for dual RAAS blockade is not recommended.
If there is an absolute indication for dual RAAS blockade, it should be performed under close professional supervision with frequent monitoring of renal function, electrolytes and BP.
The concomitant use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal insufficiency (FFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients;
The concomitant use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Neutropenia/agranulocytosis/thrombocytopenia/anemia
Neutropenia/agranulocytosis, thrombocytopenia and anemia may occur with ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare.
Particular caution should be exercised when prescribing Equipress in patients with systemic connective tissue disease, while taking immunosuppressants, allopurinol or procainamide or in combination of these risk factors, especially in patients with impaired renal function.
Some patients have had severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing Equapress in such patients, it is recommended that the plasma leukocyte count be monitored periodically.
Patients should tell their physician about any signs of infectious disease (e.g., sore throat, fever).
Midral stenosis/ aortic stenosis/hypertrophic cardiomyopathy
The ACE inhibitors should be prescribed with caution in patients with mitral stenosis and in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy).
Hepatic failure
Cholestatic jaundice occurs very rarely with ACE inhibitors. If this syndrome progresses, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of this syndrome is unclear. If jaundice or significant increase in “hepatic” enzymes activity occurs with ACE inhibitors, Equapress should be discontinued and the patient should be closely monitored.
Ethnic differences
Patients of the Negro race are more likely than those of other races to develop angioedema while taking ACE inhibitors. ACE inhibitors may have less pronounced antihypertensive effects in non-Hispanic patients compared to other races.
It is possible that this difference is due to the fact that patients with arterial hypertension of the non-Hispanic race are more likely to have low renin activity.
Lactose
The drug contains lactose monohydrate, so it should not be taken in patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
There are no data on the effect of Equapress on driving and operating machinery.
In view of the possibility of BP decrease and the risk of dizziness, somnolence and similar side effects, patients should be careful when performing potentially dangerous activities requiring special attention and quick reactions (driving, working with moving mechanisms, work of dispatcher and operator, etc.).
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Contraindications
– Hypersensitivity to amlodipine or other dihydropyridine derivatives.
– Hypersensitivity to lisinopril or other ACE inhibitors.
– Hypersensitivity to indapamide or other sulfonamide derivatives.
– Hypersensitivity to excipients of the drug.
– Severe arterial hypotension (systolic BP below 90 mm Hg).
– Past angioedema, including that associated with the use of ACE inhibitors.
– Hereditary or idiopathic angioedema.
– Severe renal insufficiency (creatinine clearance < 30 ml/min).
– Hepatic encephalopathy or severe liver function disorders.
– Hypokalemia.
– Hemodynamically significant left ventricular outflow tract obstruction (e.g., severe aortic stenosis, hypertrophic obstructive cardiomyopathy), hemodynamically significant mitral stenosis.
– Hemodynamically unstable heart failure after myocardial infarction.
– Shock (including cardiogenic).
– Unstable angina (except for Prinzmetal angina).
– Concomitant use of Equapress and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area).
– Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.
– Pregnancy and breastfeeding.
– Age less than 18 years (efficacy and safety not established).
– Hereditary lactose intolerance, galactosemia, glucose-galactose malabsorption syndrome.
Side effects
The most common adverse reactions reported with treatment with amlodipine, indapamide, and lisinopril as monotherapy were: Dizziness, headache, somnolence, visual disturbances, tinnitus, palpitations, blood “rushes” to the facial skin, decreased BP (and effects associated with hypotension), cough, shortness of breath Gastrointestinal disorders (abdominal pain, constipation, diarrhea, nausea, dyspepsia, vomiting), maculopapular rash, muscle cramps, swollen ankles, asthenia, edema and fatigue.
The following adverse drug reactions (ADRs) have been reported during the separate use of amlodipine 1, indapamide 2 and lisinopril 3.
The frequency was determined as follows:
Very frequently, 1/10 of prescriptions (≥10%).
Frequent – 1/100 appointments (≥1% and < 10%).
Infrequent – 1/1000 appointments (≥0.1% and < 1%).
Rarely, 1/10000 appointments (≥0.01% and < 0.1%).
Very rarely, less than 1/10000 appointments (< 0.01%).
The frequency is unknown (frequency cannot be estimated from available data).
Within each frequency group, adverse reactions are presented in decreasing order of importance.
Disorders of the blood and lymphatic system
decrease in hemoglobin3(rare), decrease in hematocrit3(rare), suppression of medullary hematopoiesis3(very rare), leukopenia1,2,3(very rare), thrombocytopenia1,2,3(very rare), Agranulocytosis2,3(very rare), aplastic anemia2(very rare), hemolytic anemia2,3(very rare), neutropenia3(very rare), anemia3(very rare), lymphadenopathy3(very rare).
Immune system disorders
Allergic reactions1(very rare), autoimmune disorders3(very rare).
Endocrine system disorders
Inadequate secretion of antidiuretic hormone syndrome3(rare).
Metabolic and nutritional disorders
Hyperglycemia1(very rare), hypoglycemia3(very rare), hypercalcemia2(very rare), decrease in potassium and development of hypokalemia2(frequency unknown), especially significant in at-risk patients (see “Precautions. “Particular indications”); hyponatremia2(frequency unknown) (see “Particular indications”).
Mental disorders
Mood lability1,3(infrequent), sleep disturbances3(infrequent), hallucinations3(infrequent), insomnia1(infrequent), anxiety1(infrequent), depression1(infrequent),3(frequency unknown), confusion1,3(rare).
Nervous system disorders
Dizziness1,3(often),headache1,3(often),2(rarely),somnolence1(often),increased fatigability2(rarely),vertigo2(rarely),3(infrequently),paresthesia2(rarely),1,3(infrequently),dysgeusia1,3(infrequently),fainting 1(infrequently),23(frequency unknown),tremor1(infrequent), hypoesthesia1(infrequent), parosmia (olfactory disturbance)3(rare), muscle hypertonicity1(very rare), peripheral neuropathy1(very rare), extrapyramidal disorders1(frequency unknown).
Visual disturbances
Visual disturbances (including diplopia) 1(often),2(frequency unknown), myopia2(frequency unknown), blurred vision2(frequency unknown).
Hearing and balance disorders
Tinnitus1(infrequent).
Cardiac disorders
palpitations1(often), 3(infrequent), myocardial infarction3(infrequent), 1(very rare), tachycardia3(infrequent), ventricular tachycardia 1(infrequent), arrhythmia1(infrequent), 2(very rare), polymorphic pirouette-type ventricular tachycardia (potentially fatal)2(frequency unknown), bradycardia1(infrequent), atrial fibrillation1(infrequent).
Vascular disorders
Orthostatic hypotension and related symptoms3(often), facial blood flushes1(often), acute cerebral circulation disorder3(infrequent) (due to marked BP reduction in high-risk patient groups), Raynaud’s syndrome3(infrequent), vasculitis1(very rare), hypotension1(infrequent), marked BP reduction2(very rare).
Respiratory system, chest and mediastinum disorders
dyspnea1 (frequent), cough1(infrequent), 3(frequent), rhinitis1,3(infrequent), bronchospasm3(very rare), allergic alveolitis3(very rare), eosinophilic pneumonia3(very rare), sinusitis3(very rare).
Gastrointestinal disorders
Abdominal pain1(often), 3(infrequent), nausea1(often),2(rare), 3( infrequent), dyspepsia1(often),3(infrequent), change in defecation rate1(often), diarrhea1,3(frequent), constipation1(often),2(rare), vomiting1,2(infrequent),3(frequent), dry mouth1(infrequent),2,3(rare), pancreatitis1,2,3(very rare), gastritis1(very rare), interstitial angioedema3(very rare), gum hyperplasia1(very rare).
Liver and biliary tract disorders
Hepatitis1(very rare),2(frequency unknown), hepatitis (including hepatic-cellular or cholestatic)3(very rare), jaundice1,3(very rare), liver failure3(very rare), possible development of hepatic encephalopathy in cases of liver failure2(frequency unknown), liver function disorder2(very rare), increased activity of “liver” enzymes*1(very rare).
(*-predominantly due to cholestasis)
Skin and subcutaneous tissue disorders
alopecia1(infrequent), 3(infrequent), hypersensitivity reactions2(frequent), maculopapular rash2(frequent), exanthema1(infrequent), purpura1,2(infrequent), skin depigmentation1(infrequent), hyperhidrosis1(infrequent),3(very rare) pruritus1,3(infrequent), rash1,3(infrequent), urticaria1(infrequent),2(very rare),3(rare), Psoriasis3(rare), erythema multiforme1,3(very rare), angioedema1,2(very rare),3(rare), exfoliative dermatitis1 (very rare), toxic epidermal necrolysis2,3(very rare), Stevens-Johnson syndrome1,2,3(very rare), Quincke’s edema1(very rare), photosensitivity1(very rare), 2(frequency unknown), vesicular vulgaris3(very rare), benign skin lymphadenosis*3(very rare), exacerbation of pre-existing acute systemic lupus erythematosus2(frequency unknown), hypersensitivity/angioneurotic edema of face, hands and feet, lips, tongue, vocal cleft and/or larynx3(rare).
(* – A symptom complex has been reported that may include one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibody (ANA) reaction, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, skin rash, photosensitivity or other skin changes).
Muscular and connective tissue disorders
Muscular cramps1(often), swollen ankles1(often), arthralgia1(infrequent), myalgia1(infrequent), back pain1(infrequent).
Kidney and urinary tract disorders
Renal dysfunction3(often), urinary distress1(infrequent), nycturia1(infrequent), rapid urination1(infrequent), acute renal failure1(rare), renal failure2(very rare), uremia3(rare), oliguria3(very rare), anuria3(very rare).
Genital and mammary disorders
Gynecomastia1(infrequent), 3(rare), impotence1,3(infrequent).
General disorders and disorders at the site of administration
Edema1(very often), increased fatigue1(often),3(infrequent), asthenia1(often),3(infrequent), chest pain1(infrequent), pain1(infrequent), malaise1(infrequent).
Impact on laboratory and instrumental findings:
Elevated creatinine and urea concentrations3(infrequent), hyperkalemia3(infrequent), hyperbilirubinemia3(rare), increased “liver” enzyme activity2(frequency unknown), 3(infrequent), hyponatremia3(rare), prolonged QT interval on ECG2(frequency unknown) (see “Interaction with other medicinal products and Special Indications), increased uric acid concentration2(frequency unknown) (see Special Indications), increased blood glucose concentration2(frequency unknown) (see Special Indications), decreased or increased body weight1(infrequent).
If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
Amlodipine overdose
Symptoms: significant BP decrease with possible development of reflex tachycardia and excessive peripheral vasodilation (there is a risk of significant and persistent hypotension, with development of shock and death).
Treatment: gastric lavage, administration of activated charcoal (especially during the first 2 hours after overdose), keeping the patient in horizontal position with elevated lower extremities, active support of cardiovascular system function, control of cardiac and pulmonary function parameters, control of circulating blood volume and diuresis.
In the absence of contraindications for restoration of vascular tone and BP it may be reasonable to prescribe vasoconstrictors. Intravenous injections of calcium gluconate may help to stop the effects of calcium channel blockade. Since amlodipine is largely bound to serum proteins, hemodialysis is ineffective in the treatment of amlodipine overdose.
Indapamide overdose
Toxic effects of indapamide in overdose have not been noted even in very high doses (up to 40 mg, i.e. 27 times the therapeutic dose).
The signs of acute poisoning with indapamide are primarily associated with disruption of water-electrolyte balance (hyponatremia, hypokalemia). Clinical symptoms of overdose may include nausea, vomiting, decreased blood pressure, seizures, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia).
Emergency measures include flushing the drug out of the body, gastric lavage, and/or administration of activated charcoal with restoration of the water-electrolyte balance.
Lisinopril overdose
Symptoms: significant decrease in BP, dry mouth, drowsiness, delayed urination, constipation, anxiety, increased irritability.
Treatment: symptomatic therapy, intravenous administration of 0.9% sodium chloride solution and, if possible, vasopressors, BP control, control of water-electrolyte balance. Hemodialysis may be performed.
Weight | 0.037 kg |
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Shelf life | 2 years. Do not use after the expiration date printed on the package. |
Conditions of storage | At a temperature not exceeding 25 ° C. Store out of the reach of children. |
Manufacturer | Gedeon Richter, Hungary |
Medication form | slow-release capsules |
Brand | Gedeon Richter |
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