Egipres, 5 mg+5 mg capsules 30 pcs

Heart failure, Hypertension (high blood pressure)

Arterial hypertension (patients who are indicated for combination therapy with amlodipine and ramipril in doses as in combination).

Active ingredient

Composition

How to take, the dosage

Overly, 1 capsule once daily, at the same time, regardless of meals.

The dose of Egipres is adjusted after previously titrated doses of the individual components of the drug: ramipril and amlodipine in patients with AH. Egipres with fixed doses of the active components should not be used for initial therapy. If patients require dose adjustment, it should be performed only with titration of doses of active components in monotherapy. Only after that can Egipres with fixed doses of the active ingredients be used in the combinations listed below.

In case of therapeutic necessity the dose of Egipres may be changed on the basis of individual dose titration of individual components: 5 mg amlodipine + 5 mg ramipril or 5 mg amlodipine + 10 mg ramipril or 10 mg amlodipine + 5 mg ramipril or 10 mg amlodipine + 10 mg ramipril.

Egipres at a dose of 10 mg amlodipine + 10 mg ramipril is the maximum daily dose of the drug, which should not be exceeded. The doses of 10 mg amlodipine + 5 mg ramipril (for amlodipine) and 5 mg amlodipine + 10 mg ramipril (for ramipril) are the maximum daily doses.

Adult patients

In patients taking diuretics, the drug should be administered with caution due to the risk of electrolyte-water imbalance. Renal function and blood potassium levels should be monitored in these patients.

Patients of advanced age and patients with renal insufficiency. Excretion of amlodipine and ramipril and its metabolites is delayed in elderly patients and patients with renal failure. Therefore, plasma creatinine and potassium should be regularly monitored in such patients. Egipres may be administered to patients with a creatinine Cl equal to or greater than 60 ml/min. When creatinine Cl is less than 60 mL/min and in patients with AH on hemodialysis, Egipres is recommended only for patients receiving 5 mg of ramipril as an optimal maintenance dose during individual dose titration. There is no need for individual dose titration of amlodipine in patients with impaired renal function. Egipres is contraindicated in patients with creatinine Cl less than 20 ml/min/1.73 m2. Changes in amlodipine plasma concentrations do not correlate with the degree of renal impairment.

Patients with hepatic impairment. Caution should be exercised when prescribing Egipres in patients with hepatic impairment due to the lack of dosing recommendations for such patients. Egipres is recommended only for patients who received 2.5 mg of ramipril as the optimal maintenance dose during individual dose titration.

Children and adolescents

Egipres should not be administered to children and adolescents less than 18 years of age because of the lack of data on the efficacy and safety of ramipril and amlodipine in these patient groups, both as monotherapy and as combination therapy.

Interaction

Amlodipine

It can be expected that enzyme inhibitors of microsomal liver oxidation (erythromycin in the young, diltiazem in the elderly, ketoconazole, itraconazole, ritonavir) will increase the blood plasma concentration of amlodipine, increasing the risk of side effects, while enzyme inducers of microsomal liver oxidation will decrease. Concomitant use of amlodipine with cimetidine does not change the pharmacokinetics of amlodipine.

Concomitant administration of 240 ml of grapefruit juice and 10 mg of oral amlodipine is not accompanied by significant changes in amlodipine pharmacokinetics. Unlike other BCAAs, no clinically significant interaction of amlodipine (III generation BCAAs) has been found when co-administered with NSAIDs, especially indomethacin.

The antianginal and antihypertensive effects of BCA may be enhanced with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates, and their antihypertensive effects may be increased with alpha 1-adrenoblockers and neuroleptics. Although in studies of amlodipine a negative inotropic effect has not usually been observed, however, some BCAAs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause QT interval prolongation (e.g., amiodarone and quinidine).

In co-administration of BCAA with lithium preparations (no data available for amlodipine) there may be increased neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine has no effect in vitro on the degree of binding to plasma proteins of digoxin, phenytoin, warfarin and indomethacin.

A single administration of aluminum/magnesium-containing antacids has no significant effect on the pharmacokinetics of amlodipine.

Single administration of 100 mg sildenafil in patients with essential hypertension has no effect on amlodipine pharmacokinetic parameters.

The repeated use of amlodipine 10 mg and atorvastatin 80 mg dose is not associated with significant changes in pharmacokinetic parameters of atorvastatin. When concomitant use of amlodipine with digoxin in healthy volunteers, serum digoxin content and renal clearance do not change. Amlodipine has no significant effect on the pharmacokinetics of ethanol when administered in a single and repeated dose of 10 mg.

Amlodipine has no effect on the change in PV caused by warfarin. Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Unrecommended combinations

. Concomitant use of dantrolene (IV), CYP3A4 cytochrome isoenzyme inducers (e.g., rifampicin, St. John’s wort) and CYP3A4 cytochrome isoenzyme inhibitors (protease inhibitors, azole antifungals, macrolides (such as erythromycin or clarithromycin), verapamil or diltiazem).

Ramipril

Contraindicated combinations

The use of certain high-flow membranes with a negatively charged surface (such as polyacrylonitrile membranes) when performing hemodialysis or hemofiltration; use of dextran sulfate in LDL apheresis – risk of severe anaphylactic reactions.

Unrecommended combinations

With potassium salts, potassium-saving diuretics (e.g., amiloride, triamterene, spironolactone) and other drugs, including with angiotensin II receptor antagonists (ARA II), trimethoprim, tacrolimus, cyclosporine – possible development of hyperkalemia (with simultaneous use, regular monitoring of serum potassium is required).

Combinations to be used with caution

With antihypertensive agents (especially diuretics) and other drugs that reduce BP (nitrates, tricyclic antidepressants, means for general and local anesthesia, ethanol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) – potentiation of antihypertensive effect. When combining with diuretics serum sodium content should be monitored.

With sleeping pills, narcotics and other analgesics – possible more pronounced BP reduction.

With vasopressor sympathomimetics (epinephrine, isoproterenol, dobutamine, dopamine) – reduction of the antihypertensive effect of ramipril, regular BP control is required.

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic GCS and other drugs that may affect hematological parameters – combined use increases the risk of leukopenia.

With lithium salts – increased serum lithium content and increased cardio- and neurotoxic effects of lithium.

With hypoglycemic agents for oral administration (sulfonylurea derivatives, biguanides), insulin – due to the decrease of insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs may increase, up to the development of hypoglycemia.

The concomitant use of the drugs containing aliskiren in patients with diabetes mellitus and renal insufficiency (creatinine Cl less than 60 ml/min), as well as with vildagliptin – due to the increased incidence of angioedema when used simultaneously with ACE inhibitors.

Combinations to be considered

With NSAIDs (indomethacin, acetylsalicylic acid) – the effect of ramipril may be impaired, the risk of increased renal function and increased serum potassium may increase.

With heparin – possible increase in serum potassium.

With sodium chloride – weakening of antihypertensive effect of ramipril and less effective treatment of CHF symptoms.

With ethanol – increase of vasodilation symptoms. Ramipril may increase the adverse effects of ethanol on the body.

With estrogens – weakening of the antihypertensive effect of ramipril (fluid retention).

Desensitizing therapy in hypersensitivity to insect venoms – ACE inhibitors, including ramipril, increase the likelihood of severe anaphylactic or anaphylactoid reactions to insect venoms.

Special Instructions

The information regarding ramipril and amlodipine applies to Egipres.

Amlodipine may be combined with thiazide diuretics, alpha- and beta-adrenoblockers, ACE inhibitors, sustained release nitrates, sublingual nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic agents in the treatment of AH.

In the treatment of angina pectoris, amlodipine may be administered in combination with other antianginal agents, including patients refractory to treatment with nitrates and/or beta-adrenoblockers in adequate doses.

Amlodipine has no adverse effects on metabolism and plasma lipids and may be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.

Amlodipine may also be used in cases where the patient is prone to vasospasm/vasoconstriction.

Patients of low body weight, short stature, and patients with significant hepatic impairment may require a lower dosage.

Weights should be monitored and a dentist should be seen during treatment (to prevent soreness, bleeding, and gum hyperplasia).

Ramipril

Hyponatremia and hypovolemia should be corrected before starting ramipril treatment. Patients who have previously taken diuretics should discontinue them or at least decrease their dose 2-3 days prior to starting ramipril (in this case the patients with CHF should be monitored regularly due to possibility of decompensation with increase in RBC).

After the first dose of the drug, as well as when increasing the dose and/or dose of diuretics (especially loop diuretics), the patient should be monitored regularly for at least 8 hours to take appropriate measures in case of excessive BP decrease.

If ramipril is used for the first time or at a high dose in patients with increased RAAS activity, their BP should be monitored regularly, especially at the beginning of treatment, since these patients have an increased risk of excessive BP reduction. In malignant AH and CH, especially in acute MI, treatment with ramipril should be started only in hospital.

In patients with CHF, administration of the drug may lead to the development of marked BP decrease, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure.

Cautions should be taken with elderly patients as they may be especially sensitive to ACE inhibitors; renal function tests should be monitored during the initial phase of therapy.

In patients in whom decreased BP may pose some risk (e.g., patients with atherosclerotic narrowing of coronary or cerebral arteries), treatment should be initiated under close medical supervision.

Cautions should be taken during physical activity and/or hot weather because of the risk of increased sweating and dehydration with the development of arterial hypotension due to decreased RBC and lower sodium levels in the blood.

Alcohol consumption is not recommended during treatment.

Transient arterial hypotension is not a contraindication to continue treatment after BP stabilization. If severe arterial hypotension occurs again, the dose should be reduced or the drug should be discontinued. There have been cases of angioedema of the face, limbs, lips, tongue, pharynx or larynx in patients treated with ACE inhibitors. If swelling of the face (lips, eyelids) or tongue, or impaired swallowing or breathing occurs, the patient should immediately stop taking the drug. Angioedema localized in the region of the tongue, pharynx or larynx (possible symptoms: impaired swallowing or breathing) may be life-threatening and requires urgent measures to control it: p/c injection of 0.3-0.5 mg or intravenous drip injection of 0.1 mg of epinephrine (under control of BP, HR and ECG) followed by administration of GCS (intravenous, intramural or oral); also recommended is intravenous administration of antihistamines (H1- and H2-histamine receptor antagonists), and if C1-esterase enzyme inactivators are insufficient, the need for C1-esterase enzyme inhibitors in addition to epinephrine may be considered. The patient should be hospitalized and monitored until symptoms have resolved, but not less than 24 h.

Patients receiving ACE inhibitors have had cases of intestinal angioedema manifested by abdominal pain with or without nausea and vomiting; in some cases facial angioedema has also been observed simultaneously. If patients present with these symptoms after treatment with ACE inhibitors, the possibility of intestinal angioedema should be considered in the differential diagnosis.

Treatment with desensitization to insect venom (bees, wasps) and simultaneous administration of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (e.g., BP decrease, dyspnea, vomiting, allergic skin reactions), which may sometimes be life-threatening. During treatment with ACE inhibitors hypersensitivity reactions to insect venom (e.g. bees, wasps) develop more quickly and are more severe. If desensitization to insect venom is necessary, the ACE inhibitor should be temporarily replaced by the appropriate drug of another class.

Life-threatening, rapidly developing anaphylactoid reactions, sometimes up to and including shock, have been described with ACE inhibitors during hemodialysis or plasmafiltration using certain high-flow membranes (such as polyacrylonitrile membranes) (see also membrane manufacturer instructions). The combined use of ramipril and these types of membranes (e.g. for emergency hemodialysis or hemofiltration) should be avoided. In this case, the use of other membranes or exclusion of ACE inhibitor administration is preferable. Similar reactions have been observed in LDL apheresis with dextran sulfate. Therefore, this method should not be used in patients receiving an ACE inhibitor. In patients with liver dysfunction, the response to treatment with ramipril may be either enhanced or impaired. Besides, in patients with severe liver cirrhosis with edemas and/or ascites, significant activation of RAAS is possible, therefore special caution should be exercised when treating these patients.

Before a surgical procedure (including dental), the surgeon/anesthesiologist should be warned about the use of an ACE inhibitor.

The use of an ACE inhibitor in patients undergoing extensive surgery and/or general anesthesia may result in a marked decrease in BP if general anesthesia agents with hypotensive effects are used. This is due to blocking of angiotensin II formation against the background of compensatory increase of renin activity. In such case, the volume of circulating fluid should be increased. It is recommended to stop taking ACE inhibitor 24 h before surgery. Based on the results of epidemiological studies, it is assumed that simultaneous administration of ACE inhibitors and insulin, as well as hypoglycemic agents for oral administration may lead to the development of hypoglycemia. The highest risk of development is observed during the first weeks of combined therapy, as well as in patients with impaired renal function.

In patients with diabetes mellitus, regular monitoring of glycemia is required, especially during the first month of therapy with ACE inhibitors.

The close monitoring of neonates who have been intrauterine exposed to ACE inhibitors is recommended for the detection of arterial hypotension, oliguria, and hyperkalemia.

In oliguria, BP and renal perfusion should be maintained by administration of appropriate fluids and vasoconstrictors.

These infants are at risk of oliguria and neurologic disorders, possibly due to decreased renal and cerebral blood flow due to the decrease in BP caused by ACE inhibitors.

Dry cough may occur during therapy with ACE inhibitors. Cough persists for a long time while taking this group of drugs and disappears after their withdrawal. If a patient has a dry cough, we should keep in mind the possible iatrogenic nature of this symptom.

Patients of the Negro race are more likely than those of other races to develop angioedema while taking ACE inhibitors. Ramipril, like other ACE inhibitors, may have less pronounced antihypertensive effects in black race patients compared to other races. It is possible that this difference is due to the fact that non-Hispanic patients with AH are more likely to have low renin activity.

The monitoring of laboratory parameters before and during treatment with ramipril (up to once a month for the first 3-6 months of treatment) includes:

– monitoring of renal function (determination of serum creatinine). During treatment with ACE inhibitors in the first weeks of treatment and thereafter, it is recommended to monitor renal function. Especially close monitoring is required for patients with CH, impaired renal function, after renal transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in presence of two kidneys (in such patients even a slight increase of serum creatinine level may be an indicator of reduced renal function).

– control of electrolytes. Regular monitoring of serum potassium is recommended. Particularly close monitoring of serum potassium is required in patients with impaired renal function, significant electrolyte-water balance disorders, CHF.

Hematological parameters control (hemoglobin, leukocyte, erythrocyte, platelet count, leukocytic formula). It is recommended to monitor general blood counts to detect possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with renal dysfunction, as well as in patients with connective tissue diseases or in patients concomitantly receiving other drugs which may alter peripheral blood count.

Contraindications

Amlodipine

Side effects

The adverse effects listed below are given according to the following gradations of their frequency of occurrence according to the WHO classification: very often – more than 1/10 (more than 10%); often – more than 1/100, but less than 1/10 (more than 1%, but less than 10%); infrequently – more than 1/1000, but less than 1/100 (more than 0.1%, but less than 1%); rarely – more than 1/10000, but less than 1/1000 (more than 0.01%, but less than 0.1%); very rarely – less than 1/10000 (less than 0.01%).

Amlodipine

CPR side: often – peripheral edema (ankles and feet), palpitations; infrequent – excessive BP decrease, orthostatic hypotension, vasculitis; rare – development or aggravation of CH; very rare – heart rhythm disorders (including bradycardia, ventricular tachycardia and atrial fibrillation), MI, chest pain, migraine.

Musculoskeletal and connective tissue disorders: infrequent – arthralgia, muscle cramps, myalgia, back pain, arthrosis; rarely – myasthenia.

CNS and peripheral nervous system disorders: often – sensation of fever and rushes of blood to the skin of the face, increased fatigue, dizziness, headache, drowsiness; infrequent – malaise, fainting, excessive sweating, asthenia, hypoesthesia, paresthesias, peripheral neuropathy, tremor, insomnia, mood swings, unusual dreams, nervousness, depression, anxiety; rare – seizures, apathy; very rare – ataxia, amnesia; some cases of extrapyramidal syndrome have been registered.

Digestive system disorders: often – abdominal pain, nausea; infrequent – vomiting, changes in defecation mode (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dry oral mucosa, thirst; rarely – gingival hyperplasia, increased appetite; very rarely – gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased liver transaminase activity, hepatitis.

Blood disorders:very rarely – thrombocytopenic purpura, thrombocytopenia, leukopenia.

Metabolic disorders:very rarely – hyperglycemia.

In the respiratory system: infrequent – shortness of breath, rhinitis; very rare – cough.

Kidney and urinary tract disorders: infrequent – rapid urination, painful urination, nicturia, impotence; very rare – dysuria, polyuria.

Allergic reactions: infrequent – skin itching, rash; very rare – angioedema, erythema multiforme, urticaria.

Others: infrequent – alopecia, tinnitus, gynecomastia, weight gain/decrease, visual disturbance, diplopia, accommodation disturbance, xerophthalmia, conjunctivitis, eye pain, perverse taste, chills, nosebleed; rare – dermatitis; very rare – parosmia, xeroderma, cold sweats, skin pigmentation disturbance.

Ramipril

Cardiac side: infrequent – myocardial ischemia, including the development of an attack of angina or MI, tachycardia, arrhythmias (occurrence or increase), palpitations, peripheral edema.

Vascular side: often – excessive decrease in BP, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncopal states; infrequently – flushes of blood to the skin of the face; rarely – occurrence or worsening of circulatory disorders against stenotic vascular lesions, vasculitis; frequency unknown – Raynaud’s syndrome.

CNS side: often – headache, sensation of lightness in the head; infrequent – dizziness, agueusia (loss of taste sensitivity), dysgeusia (disruption of taste sensitivity), paresthesia (burning sensation); rarely – tremor, balance disorder; frequency unknown – cerebral ischemia, including ischemic stroke and transient cerebral circulation disorder, psychomotor reactions, parosmia (disruption of smell perception).

Visual organ: infrequent – visual disturbances, including blurred vision; rarely – conjunctivitis.

Hearing organ: rarely – hearing disorders, tinnitus.

Psychiatric disorders: infrequent – depressed mood, anxiety, nervousness, motor restlessness, sleep disturbances, including drowsiness; rare – confusion; frequency unknown – impaired concentration.

The respiratory system:often – dry cough (increased at night and when lying down), bronchitis, sinusitis, shortness of breath; infrequently – bronchospasm, including aggravation of the course of bronchial asthma, nasal congestion.

The digestive system:often – inflammatory reactions in the stomach and intestines, digestive disorders, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting; infrequently – pancreatitis, including. lethal (cases of pancreatitis with lethal outcome while taking ACE inhibitors were extremely rarely observed), increased pancreatic enzyme activity in blood plasma, intestinal angioneurotic edema, abdominal pain, gastritis, constipation, dry oral mucosa; rarely – glossitis; frequency unknown – aphthous stomatitis (inflammatory reaction of the oral mucosa).

Hepatobiliary system disorders: infrequent – increased activity of liver enzymes and content of conjugated bilirubin in blood plasma; rare – cholestatic jaundice, hepatocellular lesions; frequency unknown – acute liver failure, cholestatic or citolytic hepatitis (fatal outcome has been observed very rarely).

Kidney and urinary tract disorders: infrequent – renal dysfunction, including development of acute renal failure, increased urine excretion, increased pre-existing proteinuria, increased blood urea and creatinine concentrations.

Reproductive system and mammary gland disorders: infrequently, transient impotence due to erectile dysfunction, decreased libido; frequency unknown, gynecomastia.

Blood and lymphatic system disorders: infrequent – eosinophilia; rare – leukopenia, including neutropenia and agranulocytosis, decreased number of red blood cells in peripheral blood, decreased hemoglobin, thrombocytopenia; frequency unknown – suppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Skin and mucous membranes: often – skin rash, particularly maculopapular; infrequently – angioedema, including. and with fatal outcome (laryngeal edema can cause airway obstruction, leading to death), skin itching, hyperhidrosis (increased sweating), rarely – exfoliative dermatitis, urticaria, onycholysis; very rare – photosensitization reactions; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (licheniform) exanthema or enanthema, alopecia.

Musculoskeletal and connective tissue disorders:often – muscle cramps, myalgia; infrequently – arthralgia.

Metabolism, nutrition and laboratory parameters:often – increased blood potassium; infrequently – anorexia, decreased appetite; frequency unknown – decreased blood sodium concentration, inadequate ADH secretion syndrome.

On the immune system: incidence unknown – anaphylactic or anaphylactoid reactions (ACE inhibition increases anaphylactic or anaphylactoid reactions to insect venoms), increased titer of antinuclear antibodies.

General disorders:often – chest pain, feeling of fatigue; infrequently – increased body temperature; rarely – asthenia (weakness).

Overdose

There is no information about overdose of Egipres.

Amlodipine

Symptoms: pronounced BP decrease with possible development of reflex tachycardia and excessive peripheral vasodilation (there is a possibility of pronounced and persistent arterial hypotension, including development of shock and death).

The treatment: administration of activated charcoal (especially during the first 2 hours after overdose), gastric lavage, elevation of the limbs, active support of cardiac function, monitoring of cardiac and lung function parameters, control of blood circulation and diuresis. To restore vascular tone and BP, if there are no contraindications, the use of vasoconstrictors may be useful. IV administration of calcium gluconate is used. Amlodipine is largely bound to serum proteins, therefore hemodialysis is ineffective.

Ramipril

Symptoms: excessive peripheral vasodilation with development of marked BP decrease, shock; bradycardia or reflex tachycardia, water-electrolyte disorders, acute renal failure, stupor.

The treatment: gastric lavage, prescription of adsorbents, sodium sulfate (if possible during the first 30 minutes). If BP is significantly decreased, the patient should be laid down, legs elevated, active support of cardiac function; administration of alpha1-adrenergic agonists (norepinephrine, dopamine) and angiotensinamide may be added to the therapy for the replenishment of the blood circulation and restoration of electrolyte balance. If bradycardia is refractory to drug treatment, a temporary artificial pacemaker may be required. In case of overdose, serum creatinine and electrolytes should be monitored. Ramiprilat is poorly excreted from the blood by hemodialysis.

Pregnancy use

The drug Egipres is contraindicated because ramipril may have adverse effects on the fetus: impaired fetal renal development, decreased fetal and neonatal BP, impaired renal function, hyperkalemia, skull bone hypoplasia, oligohydramnios, limb contracture, skull bone deformation, lung hypoplasia. Pregnancy should be excluded before starting the drug in women of childbearing age.

If a woman plans to become pregnant, treatment with the drug should be discontinued. If a woman becomes pregnant during treatment with the drug, the drug should be discontinued as soon as possible and the patient should be switched to another drug with the lowest risk to the baby.

If treatment with the drug is necessary during breastfeeding, it should be discontinued (data on excretion of amlodipine and ramipril with the breast milk of women are not available).

Fertility

Amlodipine Reversible biochemical changes in sperm heads have been observed in some patients receiving BKC. Clinical data are insufficient to assess the potential effect of amlodipine on fertility.