Egipres, 5mg+5mg capsules 30pcs

Composition

Capsules are solid gelatin, CONI-SNAP 3, self-closing, with a light burgundy base and lid; the contents of the capsules are a mixture of granules and powders of white or almost white color, without or almost odorless. 1 capsule of amlodipine bezylate 6.95 mg, which corresponds to the content of amlodipine 5 mg ramipril 5 mg

Excipients:

crospovidone-20 mg,

hypromellose-1.18 mg,

microcrystalline cellulose-114.82 mg,

glyceryl dibegenate-2.05 mg.

Solid gelatin capsule composition (CONI-SNAP 3), cap and base color code 51072:

diamond blue dye (E133), charming red dye (E129), titanium dioxide, gelatin.

Pharmacological action

Antihypertensive combination agent (ACE inhibitor+BMCC)

Indications

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

Use during pregnancy and lactation

Egipres is contraindicated because ramipril may have adverse effects on the fetus: impaired fetal kidney development, decreased fetal and neonatal blood pressure, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnion, limb contracture, cranial bone deformity, and lung hypoplasia. Before starting taking the drug in women of childbearing age, pregnancy should be excluded.

If a woman is planning pregnancy, then treatment with the drug should be discontinued. If pregnancy occurs during treatment with the drug, you should stop taking it as soon as possible and transfer the patient to other medications that will reduce the risk to the child.

If treatment with the drug is necessary during breastfeeding, it should be discontinued (there are no data on the elimination of amlodipine and ramipril in breast milk of women).

Fertility

Amlodipine.  Reversible biochemical changes in sperm heads were observed in some patients treated with BCC. Clinical data are insufficient to assess the potential effect of amlodipine on fertility.

Contraindications

Amlodipine

• increased sensitivity to amlodipine and other derivatives of dihydropyridine;
• severe hypotension (SBP less than 90 mm Hg. calendar), shock (including cardiogenic);
• obstructive process that impede the ejection of blood from the left ventricle (e. g., clinically significant aortic stenosis);
• hemodynamically unstable heart failure after myocardial infarction;
• pregnancy;
• breastfeeding;
• age to 18 years (safety and effectiveness are not determined).

Ramipril

• hypersensitivity to ramipril, other ACE inhibitors;
• a history of angioedema (hereditary or idiopathic and associated with previous therapy with ACE inhibitors);
• hemodynamically significant renal artery stenosis (bilateral or unilateral, in the case of a solitary kidney);
• hypotension (SBP less than 90 mm Hg. Hg), or condition with unstable hemodynamics;
• hemodynamically significant stenosis of the aortic or mitral valve disease or hypertrophic obstructive cardiomyopathy;
• primary aldosteronism;
• severe renal insufficiency (Cl creatinine 2);
• hemodialysis (clinical experience is insufficient);
• nephropathy, treatment of which is corticosteroids, NSAIDs, immunomodulators and/or other cytotoxic agents (clinical experience is insufficient);
• decompensated chronic heart failure (clinical experience is insufficient);
• hemodialysis or hemofiltration by the use of certain types of membranes with negatively charged surface, such as high-flow membrane of polyacrylnitrile (risk of hypersensitivity reactions);
• LDL apheresis using dextran sulfate (risk of hypersensitivity reactions);
• desensitizing therapy for hypersensitivity reactions to poisons insects — bees, wasps;
• acute phase of myocardial infarction in patients with diseases such as severe heart failure (IV functional class NYHA); life-threatening ventricular arrhythmias; heart lung;
• concomitant use of drugs containing aliskiren, in patients with impaired renal function (Cl creatinine less than 60 ml/min) and patients with diabetes mellitus;
• pregnancy;
• breastfeeding;
• age to 18 years (clinical experience is insufficient).

Amlodipine + ramipril

• hypersensitivity to excipients included in the drug;
• renal failure (creatinine clearance 2);
• pregnancy;
• breast-feeding period;
• age up to 18 years (experience of clinical use is insufficient).

Use caution for the combination of amlodipine + ramipril:  atherosclerotic lesions of the coronary and cerebral arteries (risk of excessive lowering of blood pressure);

increased activity of the RAAS, in which the inhibition of the enzyme there is a risk of a sharp decline in blood pressure with kidney function impairment;

severe, especially malignant hypertension;

CHF, particularly serious or for which other drugs are taken with antihypertensive effect;

unilateral hemodynamically significant renal artery stenosis (in the presence of both kidneys);

prior to the use of diuretics; violations of water-electrolyte balance, a decrease in BCC (including in patients receiving diuretics, salt-free diet, diarrhoea, vomiting, profuse sweating);

concurrent use with drugs containing aliskiren (if dual blockade of RAAS increases the risk of a sharp decline in blood pressure, hyperkalemia and deterioration of renal function);

the liver (lack of experience of application: might as strengthening and weakening effects of ramipril; in the presence in patients of liver cirrhosis with ascites and edema may be a significant activation of the RAAS);

the impairment of renal function (Cl creatinine of more than 20 ml/min); condition after kidney transplantation;

systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the peripheral blood (including allopurinol, procainamide) — possible inhibition of bone marrow hematopoiesis, the development of neutropenia or agranulocytosis;

diabetes mellitus (risk of hyperkalemia);

older age (risk of increased antihypertensive action);

hyperkalemia;

hyponatremia;

non-ischemic etiology of CHF III–IV functional class NYHA classification;

aortic stenosis;

the syndrome of weakness of the sinus node;

mitral stenosis;

arterial hypotension;

the only functioning kidney;

renovascular hypertension;

the simultaneous use of dantrolene, estramustine, potassium-sparing diuretics and potassium supplements, potassium-containing substitutes salt, lithium preparations;

surgery/General anesthesia;

the hemodialysis with the use of high-flow membranes (e. g. AN69).

Side effects

The undesirable effects listed below are given according to the following gradations of their 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

From the CCC side: often-peripheral edema (ankles and feet), palpitation sensation; infrequently-excessive decrease in blood pressure, orthostatic hypotension, vasculitis; rarely – development or aggravation of HF; very rarely – cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), MI, chest pain, migraine.

Musculoskeletal and connective tissue disorders: infrequently-arthralgia, muscle cramps, myalgia, back pain, osteoarthritis; rarely-myasthenia gravis.

From the central nervous system and peripheral nervous system: often is the feeling of warmth and flushing to the skin, fatigue, dizziness, headache, drowsiness; rarely, malaise, syncope, excessive sweating, asthenia, hypoesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, anxiety; rarely — convulsions, apathy; very rarely — ataxia, amnesia, occasional cases of extrapyramidal syndrome.

From the digestive system: often — abdominal pain, nausea, vomiting; infrequently — vomiting, change the mode of defecation (including constipation, flatulence), indigestion, diarrhea, anorexia, dryness of the mucous membrane of the mouth, thirst; rare — gingival hyperplasia, increased appetite; very rarely — gastritis, pancreatitis, hyperbilirubinemia, jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis.

From the blood side:  very rarely — thrombocytopenic purpura, thrombocytopenia, leukopenia.

Metabolic disorders:  very rarely — hyperglycemia.

Respiratory system disorders: infrequently-shortness of breath, rhinitis; very rarely — cough.

From the side of the kidneys and urinary tract:  infrequently-frequent urination, painful urination, nocturia, impotence; very rarely-dysuria, polyuria.

Allergic reactions: infrequently – skin pruritus, rash; very rarely-angioedema, erythema multiforme, urticaria.

Other services: infrequently-alopecia, tinnitus, gynecomastia, weight gain/loss, visual impairment, diplopia, accommodation disorders, xerophthalmia, conjunctivitis, eye pain, taste distortion, chills, nosebleeds; rarely-dermatitis; very rarely-parosmia, xeroderma, cold sweat, skin pigmentation disorder.

Ramipril

From the side of the heart: infrequently — myocardial ischemia, including the development of an angina attack or MI, tachycardia, arrhythmias (appearance or increase), palpitation, peripheral edema.

From the side of blood vessels: often-excessive decrease in blood pressure, violation of orthostatic regulation of vascular tone (orthostatic hypotension), syncopal states; infrequently-flushes of blood to the skin of the face; rarely-occurrence or increase of circulatory disorders against the background of stenosing vascular lesions, vasculitis; frequency unknown-Raynaud’s syndrome.

From the central nervous system: often — headache, a feeling of lightness in the head; infrequently — dizziness, ageusia (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), paresthesia (burning sensation); rarely tremor, impaired balance; frequency unknown — cerebral ischemia, including ischemic stroke and transient ischemic stroke, impaired psychomotor reactions, parosmia (violation of the perception of odors).

From the side of the visual organ: infrequently-visual disturbances, including blurred vision; rarely-conjunctivitis.

From the side of the hearing organ: rarely — hearing disorders, ringing in the ears.

From the side of the psyche: infrequently — depressed mood, anxiety, nervousness, motor restlessness, sleep disorders, including drowsiness; rarely-confusion; frequency unknown-impaired concentration of attention.

Respiratory system disorders: often — dry cough (worse at night and lying down), bronchitis, sinusitis, shortness of breath; infrequently — bronchospasm, including worsening of the course of bronchial asthma, nasal congestion.

From the digestive system: often the inflammatory response in the stomach and intestines, indigestion, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; rarely — pancreatitis, including fatal (cases of pancreatitis with a fatal outcome when receiving ACE inhibitors have been observed very rarely), increased activity of pancreatic enzymes in blood plasma, intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the mucous membrane of the mouth; rarely — glossitis; frequency unknown — aphthous stomatitis (inflammatory reaction of the mucous membrane of the oral cavity).

From the side of the hepatobiliary system: infrequently-increased activity of liver enzymes and the content of conjugated bilirubin in blood plasma; rarely-cholestatic jaundice, hepatocellular lesions; frequency unknown-acute liver failure, cholestatic or cytolytic hepatitis (fatal outcome was extremely rare).

From the side of the kidneys and urinary tract: infrequently-impaired renal function, including the development of acute renal failure, increased urinary excretion, increased pre-existing proteinuria, increased urea and creatinine concentrations in the blood.

From the side of the reproductive system and mammary glands: infrequently — transient impotence due to erectile dysfunction, decreased libido; frequency unknown-gynecomastia.

Blood and lymphatic system disorders: infrequently — eosinophilia; rarely-leukopenia, including neutropenia and agranulocytosis, a decrease in the number of red blood cells in the peripheral blood, a decrease in hemoglobin, thrombocytopenia; frequency unknown — inhibition of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

From the skin and mucous membranes: often — skin rash, in particular maculopapular; rarely, angioneurotic edema, including fatal (edema of the larynx can cause obstruction of the Airways, leading to death), pruritus, hyperhidrosis (excessive sweating); rarely exfoliative dermatitis, urticaria, onycholysis; very rarely — photosensitivity reactions; frequency unknown — toxic epidermal necrolysis, and Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of psoriasis, dermatitis psoriasiform, lichenoid, or pemphigidae (Isaevicha) rash or enanthema, alopecia.

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

From the side of metabolism, nutrition and laboratory parameters: often-increased blood potassium; infrequently — anorexia, decreased appetite; frequency unknown-decreased blood sodium concentration, syndrome of inadequate ADH secretion.

From the immune system: the frequency is unknown — anaphylactic or anaphylactoid reactions (when ACE inhibition increases the number of anaphylactic or anaphylactoid reactions to insect poisons), an increase in the titer of antinuclear antibodies.

General violations: often-chest pain, feeling tired; infrequently-fever; rarely-asthenia (weakness).

Interaction

Amlodipine

It can be expected that inhibitors of microsomal liver oxidation enzymes (erythromycin in the young, diltiazem in the elderly, ketoconazole, itraconazole, ritonavir) will increase the concentration of amlodipine in blood plasma, increasing the risk of side effects, and inducers of microsomal liver oxidation enzymes will decrease. When amlodipine is co-administered with cimetidine, the pharmacokinetics of amlodipine do not change.

Simultaneous single use of 240 ml of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. Unlike other BCAAs, there was no clinically significant interaction of amlodipine (generation III BCAAs) when co-administered with NSAIDs, especially Indometacin.

It is possible to enhance the antianginal and antihypertensive effects of BCC when combined with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-blockers and nitrates, as well as increase their antihypertensive effect when combined with alpha-1-blockers, neuroleptics. Although no negative inotropic effect has usually been observed in the study of amlodipine, however, some BCCs may increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (for example, amiodarone and quinidine).

When BCC is co-administered with lithium preparations (no data available for amlodipine), their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Amlodipine does not affect in vitro the degree of binding to plasma proteins of digoxin, phenytoin, warfarin and Indometacin.

A single dose of aluminum / magnesium-containing antacids does not significantly affect the pharmacokinetics of amlodipine.

A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetics of amlodipine.

Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin. When amlodipine was co-administered with digoxin in healthy volunteers, the serum digoxin content and its renal clearance did not change. With a single and repeated use at a dose of 10 mg, amlodipine does not significantly affect the pharmacokinetics of ethanol.

Amlodipine does not affect the change in PV caused by warfarin. Amlodipine does not cause significant changes in the pharmacokinetics of cyclosporine.

Not recommended combinations

Concomitant use of dantrolene (iv use), inducers of cytochrome CYP3A4 isoenzymes (for example rifampicin, St. John’s wort preparations) and inhibitors of cytochrome CYP3A4 isoenzymes (protease inhibitors, azole antifungal drugs, macrolides (for example erythromycin or clarithromycin), verapamil or diltiazem).

Ramipril

Contraindicated combinations

Application of some high-flow membranes with a negatively charged surface (e. g. polyacrylonitrile membranes) during hemodialysis or hemofiltration; the use of dextran sulfate in LDL apheresis — the risk of severe anaphylactic reactions.

Not recommended combinations

With potassium salts, potassium-sparing diuretics (for example, amiloride, triamterene, spironolactone) and other drugs, including angiotensin II receptor antagonists (ARA II), trimethoprim, tacrolimus, cyclosporine – hyperkalemia may develop (with simultaneous use, regular monitoring of serum potassium content is required).

Combinations that should be used with caution

With antihypertensive agents (especially diuretics) and other drugs that reduce blood pressure (nitrates, tricyclic antidepressants, general and local anesthesia, ethanol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin) — potentiation of the antihypertensive effect. When combined with diuretics, serum sodium levels should be monitored.

With sleeping pills, narcotic drugs, and other painkillers, a more pronounced decrease in blood pressure is possible.

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

With allopurinol, procainamide, cytostatics, immunosuppressants, systemic corticosteroids and other agents that may affect hematological parameters-combined use increases the risk of leukopenia.

With lithium salts-an increase in the content of lithium in the serum and an increase in the cardio – and neurotoxic effects of lithium.

With hypoglycemic agents for oral use (sulfonylureas, biguanides), insulin-due to a decrease in insulin resistance under the influence of ramipril, it is possible to increase the hypoglycemic effect of these drugs, up to the development of hypoglycemia.

Concomitant use of drugs containing aliskiren in patients with diabetes mellitus and renal insufficiency (creatinine clearance less than 60 ml / min), as well as with vildagliptin-due to an increase in the frequency of angioedema when used simultaneously with ACE inhibitors.

Combinations to take into account

With NSAIDs (Indometacin, acetylsalicylic acid) – it is possible to weaken the effect of ramipril, increase the risk of impaired renal function and increase the content of potassium in the blood serum.

With heparin — it is possible to increase the content of potassium in the blood serum.

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

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

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

Desensitizing therapy for hypersensitivity to insect poisons-ACE inhibitors, including ramipril, increase the likelihood of developing severe anaphylactic or anaphylactoid reactions to insect poisons.

How to take, course of use and dosage

Inside,1 capsule 1 time a day, at the same time, regardless of food intake.

The dose of Egipres is selected after previously titrated doses of individual components of the drug: ramipril and amlodipine in patients with hypertension. Egipres with fixed doses of active ingredients cannot be used for initial therapy. If patients need dose adjustment, then it should be carried out only by titrating the doses of active components in monotherapy. Only after that it is possible to use the drug Aegipres with fixed doses of active ingredients in the following combinations.

If necessary, the dose of Egipres can be changed based on individual titration of the individual components: 5 mg of amlodipine + 5 mg of ramipril or 5 mg of amlodipine + 10 mg of ramipril or 10 mg of amlodipine + 5 mg of ramipril or 10 mg of amlodipine + 10 mg of ramipril.

Egipres at a dose of 10 mg of amlodipine + 10 mg of ramipril is the maximum daily dose of the drug, which is not recommended to be exceeded. Dosages of 10 mg of amlodipine + 5 mg of ramipril (according to amlodipine) and 5 mg of amlodipine + 10 mg of ramipril (according to ramipril) are the maximum daily doses.

Adult patients

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

Elderly patients and patients with renal insufficiency. The elimination of amlodipine and ramipril and its metabolites in elderly patients and patients with renal insufficiency is slowed. Therefore, in such patients, it is necessary to regularly monitor the content of creatinine and potassium in the blood plasma. Egipres can be prescribed to patients with a creatinine clearance equal to or greater than 60 ml / min. When creatinine clearance is less than 60 ml/min, as well as in patients with hypertension on hemodialysis, Aegipres is recommended only for patients who received 5 mg of ramipril, as the optimal maintenance dose during titration of the individual dose. There is no need to titrate the individual dose of amlodipine in patients with impaired renal function. Egipres is contraindicated in patients with a creatinine clearance of less than 20 ml / min/1.73 m2. Changes in the concentration of amlodipine in blood plasma do not correlate with the severity of renal failure.

Patients with hepatic insufficiency. Caution should be exercised when prescribing Aegipres to patients with hepatic insufficiency due to the lack of recommendations on the dosage of the drug in such patients. Aegipres is recommended only for patients who received 2.5 mg of ramipril as the optimal maintenance dose during the individual dose titration process.

Children and teenagers

Egipres should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the efficacy and safety of ramipril and amlodipine in these groups of patients, both as monotherapy and as combination therapy.

Overdose

There is no information about overdose of Egipres.

Amlodipine

Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (there is a possibility of severe and persistent arterial hypotension, including shock and death).

Treatment: use of activated charcoal (especially in the first 2 hours after an overdose), gastric lavage, elevation of the limbs, active maintenance of CVS functions, monitoring of heart and lung performance, control of BCC and diuresis. To restore vascular tone and blood pressure, if there are no contraindications, the use of vasoconstrictor drugs may be useful. Use intravenous use of calcium gluconate. Amlodipine is largely bound to serum proteins, so hemodialysis is ineffective.

Ramipril

Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia or reflex tachycardia, water and electrolyte disorders, acute renal failure, stupor.

Treatment: gastric lavage, use of adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a marked decrease in blood pressure, the patient should be laid down, legs raised, and CVS functions actively supported; the use of alpha-1-adrenergic agonists (norepinephrine, dopamine) and angiotensinamide can also be added to therapy to replenish BCC and restore electrolyte balance. If bradycardia is refractory to medical treatment, it may be necessary to install a temporary artificial pacemaker. In case of overdose, it is necessary to monitor the content of creatinine and electrolytes in the blood serum. Ramiprilate is poorly excreted from the blood by hemodialysis.

Special instructions

Information related to ramipril and amlodipine is applicable to Aegipres.

Amlodipine

In the treatment of hypertension, amlodipine may be combined with thiazide diuretics, alpha-and beta-blockers, ACE inhibitors, prolonged-acting nitrates, sublingual nitroglycerin, NSAIDs, antibiotics, and oral hypoglycemic agents.

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

Amlodipine does not have any adverse effects on the metabolism and plasma lipids and can be used in the treatment of patients with bronchial asthma, diabetes mellitus and gout.

Amlodipine can also be used in cases where the patient is predisposed to vasospasm/vasoconstriction.

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

During treatment, it is necessary to monitor body weight and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

Ramipril

Before starting treatment with ramipril, hyponatremia and hypovolemia should be eliminated. Patients who have previously taken diuretics should cancel them or at least reduce their dose 2-3 days before starting ramipril (in this case, the condition of patients with CHF should be regularly monitored due to the possibility of decompensation with an increase in BCC).

After taking the first dose of the drug, as well as when increasing its dose and / or the dose of diuretics (especially loop diuretics), it is necessary to ensure regular medical monitoring of the patient for at least 8 hours in order to take timely appropriate measures in case of an excessive decrease in blood pressure.

If ramipril is used for the first time or at a high dose in patients with increased RAAS activity, then their blood pressure should be regularly monitored, especially at the beginning of treatment, since these patients have an increased risk of excessive blood pressure reduction. In patients with malignant hypertension and HF, especially in the acute stage of MI, treatment with ramipril should be initiated only in a hospital setting.

In patients with CHF, taking the drug can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia, and rarely-the development of acute renal failure.

Caution should be exercised in the treatment of elderly patients, as they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment, it is recommended to monitor the indicators of renal function.

In patients for whom a decrease in blood pressure may pose a certain risk (for example, patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision.

Caution should be exercised during exercise and / or hot weather because of the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in BCC and a decrease in blood sodium.

During treatment, it is not recommended to drink alcohol.

Transient arterial hypotension is not a contraindication for continuing treatment after BP stabilization. In case of repeated occurrence of severe hypotension, the dose should be reduced or the drug should be discontinued. Angioedema of the face, extremities, lips, tongue, pharynx, or larynx has been reported in patients treated with ACE inhibitors. If there is swelling in the face (lips, eyelids) or tongue, or if swallowing or breathing is impaired, the patient should immediately stop taking the drug. Angioedema localized in the tongue, pharynx or larynx (possible symptoms: swallowing or breathing disorders) can be life–threatening and requires urgent measures to stop it: subcutaneous use of 0.3 – 0.5 mg or intravenous drip use of 0.1 mg of epinephrine (under the control of blood pressure, heart rate and ECG), followed by the use of corticosteroids (iv, iv or inside); intravenous use of antihistamines (H1-and H2-histamine antagonists) is also recommended. C1-esterase inhibitors may be considered in addition to epinephrine, and in the case of insufficient C1-esterase inactivators. The patient should be hospitalized and monitored until symptoms are completely relieved, but not less than 24 hours.

In patients treated with ACE inhibitors, cases of intestinal angioedema were observed, which was manifested by abdominal pain with or without nausea and vomiting; in some cases, angioedema of the face was also observed simultaneously. If a patient develops the above symptoms during treatment with ACE inhibitors, the possibility of developing intestinal angioedema should also be considered during the differential diagnosis.

Treatment aimed at desensitization to insect venom (bees, wasps) and simultaneous use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (for example, a decrease in blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening. Against the background of treatment with ACE inhibitors, hypersensitivity reactions to insect venom (for example, bees, wasps) develop faster and are more severe. If desensitization to insect venom is necessary, the ACE inhibitor should be temporarily replaced with a corresponding drug of a different class.

When using ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions have been described, sometimes up to the development of shock during hemodialysis or plasma filtration using certain high-flow membranes (for example, polyacrylonitrile membranes) (see also the instructions of membrane manufacturers). It is necessary to avoid the combined use of ramipril and such membranes (for example, for urgent hemodialysis or hemofiltration). In this case, it is preferable to use other membranes or exclude the use of an ACE inhibitor. Similar reactions were observed in LDL apheresis with dextran sulfate. Therefore, this method should not be used in patients receiving an ACE inhibitor. In patients with impaired liver function, the response to treatment with ramipril may be either enhanced or weakened. In addition, in patients with severe cirrhosis of the liver with edema and / or ascites, significant activation of the RAAS is possible, so special care should be taken when treating these patients.

Before surgery (including dental surgery), 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 lead to a marked decrease in blood pressure if general anesthesia agents with a hypotensive effect are used. This is due to blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. In this case, the volume of circulating fluid should be increased. It is recommended to stop taking an ACE inhibitor 24 hours before surgery. Based on the results of epidemiological studies, it is assumed that simultaneous use of ACE inhibitors and insulin, as well as hypoglycemic agents for oral use, may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function.

In patients with diabetes mellitus, regular glycemic control is required, especially during the first month of ACE inhibitor therapy.

Careful monitoring of newborns who have been exposed to intrauterine ACE inhibitors is recommended to detect hypotension, oliguria, and hyperkalemia.

With oliguria, it is necessary to maintain blood pressure and renal perfusion by introducing appropriate fluids and vasoconstrictors.

These newborns are at risk of developing oliguria and neurological disorders, possibly due to reduced renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

During ACE inhibitor therapy, a dry cough may occur. Cough persists for a long time against the background of taking drugs of this group and disappears after their cancellation. If a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom.

Patients of the black race are more likely than those of other races to develop angioedema while taking ACE inhibitors. Ramipril, like other ACE inhibitors, may have a less pronounced antihypertensive effect in black patients compared to representatives of other races. Perhaps this difference is due to the fact that black patients with hypertension often have low renin activity.

Monitoring of laboratory parameters before and during treatment with ramipril (up to 1 time per month in the first 3-6 months of treatment) includes:

– monitoring of renal function (determination of serum creatinine). During treatment with ACE inhibitors, monitoring of renal function is recommended during the first weeks of treatment and thereafter. Especially careful monitoring is required in patients with HF, impaired renal function, after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis with two kidneys (in such patients, even a slight increase in serum creatinine levels can be an indicator of decreased renal function).

– monitoring of the electrolyte content. Regular monitoring of serum potassium is recommended. Especially careful monitoring of the potassium content in the blood serum is required in patients with impaired renal function, significant violations of the water-electrolyte balance, CHF.

– control of hematological parameters (hemoglobin content, the number of white blood cells, red blood cells, platelets, leukocyte formula). It is recommended to monitor the indicators of a general blood test to detect possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients receiving other drugs that can change the peripheral blood picture at the same time.

Monitoring the number of white blood cells is necessary for early detection of leukopenia, which is especially important in patients with an increased risk of developing it, as well as at the first signs of infection. If neutropenia is detected (neutrophil count is less than 2000/µl), discontinuation of ramipril treatment is required. If symptoms due to leukopenia appear (for example, fever, enlarged lymph nodes, tonsillitis), urgent monitoring of the peripheral blood picture is necessary. In case of signs of bleeding (small petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to monitor the number of platelets in the peripheral blood.

– determination of the activity of liver enzymes, bilirubin concentration in the blood. If jaundice or a significant increase in the activity of liver enzymes occurs, ramipril treatment should be discontinued and the patient should be monitored by a doctor.

Influence on the ability to drive vehicles and manage mechanisms. During treatment with the drug, it is recommended to refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions (dizziness is possible, especially at the beginning of treatment, and in patients taking diuretic drugs, a decrease in concentration of attention) After the first dose, as well as after a significant increase in the dose of the drug, it is not recommended to drive vehicles and work with technical equipment for several hours.

Storage conditions

At a temperature not exceeding 25 C.

Active ingredient

Amlodipine, Ramipril

Conditions of release from pharmacies

By prescription

Dosage form

capsules

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Hypertension