Egipres capsules 5mg + 10mg №30

Indications

- arterial hypertension (to patients who have been shown combination therapy with Amlodipine and Ramipril in doses appropriate to the drug Egipres^®).

Dosage and administration

Egipres^® prescribed inside for adults 1 capsule 1 time / day, at the same time, regardless of the meal.

Egipres dose^® selected after a previous titration of doses of individual components of the drug ramipril and amlodipine in patients with arterial hypertension. Egipres^® with fixed doses of active ingredients is not used for initial therapy. If patients need dose adjustment, then it should be carried out only by titrating doses of the active components in monotherapy. Only after that it is possible to use the drug Egipres^® with fixed doses of active ingredients in the combinations below

With therapeutic need dose of the drug Egipres^® can be changed on the basis of individual titration of doses of 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.

The maximum daily dose of the drug Egipres^® makes 10 mg of amlodipine + 10 mg of ramipril; exceeding the maximum dose is not recommended.Dosages of 10 mg of amlodipine + 5 mg of ramipril (for amlodipine) and 5 mg of amlodipine + 10 mg of ramipril (for ramipril) are the maximum daily doses.

Precautions should be prescribed to patients receiving diuretics, due to the risk of impaired water and electrolyte balance. In these patients, kidney function and potassium should be monitored.

Have elderly patients and patients with renal failure elimination of amlodipine and ramipril and its metabolites is slowed down. Therefore, in these patients it is necessary to regularly monitor the content of creatinine and potassium in the blood plasma. Egipres^® can be administered to patients with QA ≥ 60 mL / min. At QC <60 ml / min, as well as patients with arterial hypertension who are on hemodialysis, Egipres^® It is recommended to appoint only if they received ramipril in a dose of 2.5 mg or 5 mg as the optimal maintenance dose during the titration of the individual dose. No need to titrate individual dose of amlodipine in patients with impaired renal function. Egipres^® contraindicated in patients with QC <20 ml / min / 1.73 m² surface area of ​​the body. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Caution should be prescribed Egipres^®in patients with liver failure due to the lack of recommendations on the dosing of the drug in these patients. Egipres^® recommended only for patients receiving ramipril in a dose of 2.5 mg as the optimal maintenance dose during the titration of the individual dose.

Adverse effects

Determination of the frequency of adverse reactions according to the WHO classification: very often -> 1/10 (> 10%); often -> 1/100, but <1/10 (> 1%, but <10%); infrequently -> 1/1000, but <1/100 (> 0.1%, but <1%); rarely> 1/10 000, but <1/1000 (> 0.01%, but <0.1%); very rarely - <1/10 000 (<0.01%).

Amlodipine

Cardiovascular: often - peripheral edema (ankles and feet), palpitations; infrequently - excessive decrease in blood pressure, orthostatic hypotension, vasculitis; rarely, development or worsening of heart failure; very rarely - cardiac arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction, chest pain, migraine.

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

Nervous system: often - a sensation of heat and hot flushes to the skin of the face, fatigue, dizziness, headache, drowsiness; infrequently - malaise, fainting, increased sweating, asthenia, hypesthesia, paresthesia, peripheral neuropathy, tremor, insomnia, mood lability, unusual dreams, nervousness, depression, anxiety; seldom - spasms, apathy; very rarely - ataxia, amnesia, isolated cases of extrapyramidal syndrome.

Gastrointestinal: often - abdominal pain, nausea; infrequently - vomiting, changes in the mode of bowel movement (including constipation, flatulence), dyspepsia, diarrhea, anorexia, dryness of the oral mucosa, thirst; rarely - gingival hyperplasia, increased appetite; very rarely - gastritis, pancreatitis,hyperbilirubinemia, jaundice (usually cholestatic), increased activity of hepatic transaminases, hepatitis.

Hemic and lymphatic: very rarely - thrombocytopenic purpura, thrombocytopenia, leukopenia.

Metabolic disorders: very rarely - hyperglycemia.

Respiratory: infrequently - shortness of breath, rhinitis, nosebleeds; very rarely - cough.

Urogenital: infrequently - frequent urination, painful urination, nocturia, impotence; very rarely - dysuria, polyuria.

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

Special senses: infrequently - tinnitus, blurred vision, diplopia, disturbance of accommodation, xerophthalmia, conjunctivitis, pain in the eyes, taste perversion; very rarely - parosmia.

Dermatologic: infrequently - alopecia; rarely - dermatitis; very rarely - xerodermia, a violation of skin pigmentation.

Other: infrequently - gynecomastia, increase / decrease in body weight, chills; very rarely - "cold" sweat.

Ramipril

Cardiovascular: often - an excessive decrease in blood pressure, impaired orthostatic regulation of vascular tone (orthostatic hypotension), syncopal conditions; infrequently - “flushes” of blood to the skin of the face, myocardial ischemia, including the development of an attack of angina pectoris or myocardial infarction, tachycardia, arrhythmias (appearance or intensification), palpitations,peripheral edema; rarely - the occurrence or enhancement of circulatory disorders on the background of stenotic vascular lesions, vasculitis; frequency not known - Raynaud's syndrome.

Nervous system: often - headache, feeling of "lightness" in the head; infrequently - dizziness, agevziya (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), paresthesia (burning sensation); rarely - tremor, imbalance; frequency is unknown - cerebral ischemia, including ischemic stroke and transient cerebral circulation disturbance, impaired psychomotor reactions, parosmia (impaired perception of smells).

Special senses: infrequently - visual impairment, including blurred vision; rarely - conjunctivitis.

From the organ of hearing: rarely - hearing loss, ringing in the ears.

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

Respiratory: 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 - inflammatory reactions in the stomach and intestines, indigestion, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting; Infrequently - pancreatitis, incl.and fatal (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), increased activity of pancreatic enzymes in the blood plasma, intestinal angioedema, edema, gastritis, constipation, dry oral mucosa; rarely - glossitis; unknown frequency - aphthous stomatitis (inflammatory reaction of the oral mucosa).

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

Urogenital: infrequently - impaired renal function, including the development of acute renal failure, an increase in the excretion of urine, an increase in pre-existing proteinuria, an increase in the concentration of urea and creatinine in the blood.

From the reproductive system: infrequently - transient impotence due to erectile dysfunction, decreased libido; frequency unknown - gynecomastia.

Hemic and lymphatic: infrequently - eosinophilia; rarely, leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, a decrease in hemoglobin, thrombocytopenia; frequency is unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia.

Skin and Subcutaneous Tissues: often - skin rash, in particular, makulo-papular; infrequently - angioedema, incl. and fatal (laryngeal edema can cause airway obstruction, leading to death), pruritus, hyperhidrosis (sweating); rarely - exfoliative dermatitis, urticaria, onycholysis; very rarely - photosensitivity reactions; frequency is unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (desiccous) exanthema or enanthema, alopecia.

From the musculoskeletal system: often - muscle cramps, myalgia; infrequently - arthralgia.

Metabolism: often - an increase in the content of potassium in the blood; infrequently - anorexia, loss of appetite; frequency is unknown - decrease in sodium concentration in the blood, syndrome of inadequate secretion of ADH.

On the part of the immune system: frequency unknown - anaphylactic or anaphylactoid reactions (with inhibition of ACE increases the number of anaphylactic or anaphylactoid reactions to insect venoms), an increase in the titer of antinuclear antibodies.

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

Contraindications

Amlodipine

- hypersensitivity to amlodipine and other dihydropyridine derivatives;

- severe hypotension (systolic blood pressure less than 90 mm Hg), shock (including cardiogenic);

- an obstructive process that impedes the release of blood from the left ventricle (for example, clinically significant aortic stenosis);

- hemodynamically unstable heart failure after myocardial infarction;

- pregnancy;

- lactation period (breastfeeding);

- children's and teenage age till 18 years (safety and efficiency are not defined).

Ramipril

- hypersensitivity to ramipril, other ACE inhibitors;

- angioedema in history (hereditary or idiopathic, as well as associated with previous therapy with ACE inhibitors);

- arterial hypotension (systolic blood pressure <90 mm Hg) or conditions with unstable hemodynamic parameters;

- hemodynamically significant stenosis of the aortic or mitral valve, or hypertrophic obstructive cardiomyopathy;

- acute stage of myocardial infarction in patients with diseases such as severe heart failure (IV functional class according to NYHA), life-threatening ventricular arrhythmias, and pulmonary heart;

- primary hyper aldosteronism;

- hemodynamically significant renal artery stenosis (bilateral or unilateral in the case of a single kidney);

- severe renal failure (CC <20 ml / min / 1.73 m²);

- hemodialysis (experience with clinical use is insufficient);

- nephropathy, the treatment of which is carried out by GCS, NSAIDs, immunomodulators and / or other cytotoxic agents (clinical experience is insufficient);

- hemodialysis or hemofiltration using some membranes with a negatively charged surface, such as high-flow polyacrylonitrile membranes (risk of hypersensitivity reactions);

- decompensated chronic heart failure (experience with clinical use is insufficient);

- LDL apheresis using dextran sulfate (risk of hypersensitivity reactions);

- desensitization therapy in case of hypersensitivity reactions to the poisons of insects - bees, wasps;

- simultaneous use of drugs containing aliskiren in patients with impaired renal function (CC less than 60 ml / min) and patients with diabetes mellitus;

- pregnancy;

- lactation period (breastfeeding);

- children's and teenage age up to 18 years (experience of clinical use is insufficient);

Amlodipine + ramipril

- hypersensitivity to the drug;

- renal failure (CC <20 ml / min / 1.73 m²);

- pregnancy;

- breastfeeding period;

- children's and teenage age up to 18 years (experience of clinical use is insufficient).

Carefully use the combination amlodipine + ramipril in the following diseases and conditions:

- atherosclerotic lesions of the coronary and cerebral arteries (the danger of an excessive decrease in blood pressure);

- increased activity of the RAAS, in which, when ACE is inhibited, there is a risk of a sharp decrease in blood pressure with a deterioration in renal function;

- severe, especially malignant arterial hypertension;

- chronic heart failure, especially severe or about which other medicines are taken with antihypertensive effect;

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

- prior diuretic intake;

- violations of water and electrolyte balance, reduction of bcc (including while taking diuretics, salt-free diet, diarrhea, vomiting, excessive sweating);

- simultaneous use with drugs containing aliskiren (with double blockade of RAAS increases the risk of a sharp decrease in blood pressure, hyperkalemia and deterioration of renal function);

- dysfunction of the liver (lack of experience with the application): both strengthening and weakening of the effects of ramipril is possible; in patients with cirrhosis of the liver with ascites and edema, significant activation of the RAAS is possible;

- impaired renal function (CC> 20 ml / min);

- condition after kidney transplantation;

- Systemic diseases of the connective tissue, incl. systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the pattern of peripheral blood (including Allopurinol, procainamide) - bone marrow hematopoiesis can be inhibited, neutropenia or agranulocytosis can develop;

- diabetes mellitus - the risk of hyperkalemia;

- old age - the risk of increased antihypertensive action;

- hyperkalemia;

- hyponatremia;

- chronic heart failure of the non-ischemic etiology of the III-IV functional class according to the NYHA classification;

- aortic stenosis;

- SSSU;

- mitral stenosis;

- arterial hypotension;

- the only functioning kidney;

- Renovascular hypertension;

- simultaneous use of dantrolen, estramustine, potassium-saving diuretics and potassium preparations, potassium-containing food salt substitutes, lithium preparations;

- surgery / general anesthesia;

- conducting hemodialysis using high-flow membranes (for example, AN69^®).

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy because ramipril can have an adverse effect on the fetus: impaired development of the kidneys of the fetus, lowering blood pressure of the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the extremities, deformation of the bones of the skull, hypoplasia of the lungs. Before starting the drug in women of childbearing age, pregnancy should be excluded.

If a woman is planning a pregnancy, treatment with the drug should be discontinued. If pregnancy occurs during drug treatment, it should be discontinued as soon as possible and the patient transferred to other drugs, the use of which will have the lowest risk for the child.

If necessary, the use of the drug during lactation breastfeeding should be discontinued.It is not known whether amlodipine and ramipril are excreted in human breast milk.

In some patients receiving Calcium channel blockers, reversible biochemical changes were observed in the heads of spermatozoa. Clinical data are insufficient to assess the potential effect of amlodipine on fertility.

Application for violations of kidney function

Contraindications: hemodynamically significant renal artery stenosis (bilateral or unilateral in the case of a single kidney); severe renal failure (CC <20 ml / min / 1.73 m²); hemodialysis (experience with clinical use is insufficient); nephropathy, the treatment of which is carried out by GCS, NSAIDs, immunomodulators and / or other cytotoxic agents (clinical experience is insufficient).

special instructions

Specific instructions for ramipril and amlodipine apply to Hypres^®.

Special instructions for taking amlodipine

In the treatment of arterial hypertension, amlodipine can be combined with the administration of thiazide diuretics, alpha- and beta-blockers, ACE inhibitors, long-acting nitrates, sublingual Nitroglycerin, NSAIDs, antibiotics and hypoglycemic means for oral administration.

In the treatment of angina, amlodipine can be prescribed in combination with other antianginal agents, including in patients 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 asthma, diabetes and gout. Amlodipine can also be used in cases where the patient is prone to vasospasm / vasoconstriction.

Patients with low body mass, short stature and patients with severe liver dysfunction may require a lower dose.

During treatment, body weight control and monitoring by a dentist is necessary (to prevent soreness, bleeding, and gingival hyperplasia).

Special instructions for taking ramipril

Before starting treatment with ramipril, it is necessary to eliminate hyponatremia and hypovolemia. Patients who have previously taken diuretics need to cancel them, or at least reduce their dose 2-3 days before starting ramipril (in this case, the condition of patients with chronic heart failure should be regularly monitored due to the possibility of their decompensation with increase in bcc).

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

If ramipril is used for the first time or in a high dose in patients with increased RAAS activity, then they should regularly monitor their blood pressure, especially at the beginning of treatment, because these patients have an increased risk of excessive blood pressure reduction.In case of malignant hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with ramipril should be started only in the hospital setting. In patients with chronic heart failure, 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 by the development of acute renal failure.

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

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

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

Alcohol is not recommended during treatment.

Transient hypotension is not a contraindication to continue treatment after stabilization of blood pressure. In the case of recurrence of severe hypotension, reduce the dose or discontinue the drug.In patients treated with ACE inhibitors, there have been cases of angioedema of the face, limbs, lips, tongue, pharynx, or larynx. In the event of swelling in the face (lips, eyelids) or tongue, or a violation of swallowing or breathing, the patient should immediately stop taking the drug. Angioedema, localized in the area of ​​the tongue, pharynx, or larynx (possible symptoms: impaired swallowing or breathing), can be life-threatening and requires urgent measures to relieve it: s / c administration 0.3-0.5 mg or IV drip 0.1 mg Epinephrine (under the control of blood pressure, heart rate and ECG), followed by the use of corticosteroids (IV, IV, or orally); It is also recommended in / in the introduction of antihistamines (histamine H antagonists₁- and H₂-receptors), and in case of insufficiency of inactivators of the enzyme C₁β-esterase, you can consider the need to introduce in addition to epinephrine inhibitors of the enzyme C₁esterase. The patient should be hospitalized and should be monitored until the symptoms are relieved, but not less than 24 hours.

In patients treated with ACE inhibitors, there were cases of intestinal angioedema, which was manifested by abdominal pains with nausea and vomiting or without them; in some cases, angioedema of the face was also observed simultaneously. When a patient with the above described symptoms appears in patients with ACE inhibitors, when a differential diagnosis is made, the possibility of developing intestinal angioedema in them should also be considered.

Treatment aimed at desensitization to the poison of insects (bees, wasps), and the simultaneous use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (for example, reduction of blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening. During treatment with ACE inhibitors, hypersensitivity reactions to insect venom (for example, bees, wasps) develop faster and are more difficult. If it is necessary to conduct desensitization to the poison of insects, then the ACE inhibitor should be temporarily replaced by the appropriate drug of another 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 instructions of membrane manufacturers). It is necessary to avoid the joint 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 using dextran sulfate. Therefore, this method should not be used in patients receiving an ACE inhibitor.

In patients with impaired liver function, the reaction to treatment with ramipril can be either enhanced or weakened.In addition, in patients with severe liver cirrhosis with edema and / or ascites, significant activation of the RAAS is possible, therefore, special care should be taken in treating these patients.

Before surgery (including dental) it is necessary to warn the surgeon / anesthesiologist about the use of an ACE inhibitor. The use of an ACE inhibitor in patients undergoing extensive surgery and / or general anesthesia can lead to a pronounced decrease in blood pressure if agents are used for general anesthesia with hypotensive action. This is due to the blocking of the formation of angiotensin II against the background of a compensatory increase in renin activity. In this case, you should increase the BCC. It is recommended to stop taking an ACE inhibitor 24 hours before surgery.

Based on the results of epidemiological studies, it is assumed that the simultaneous intake of ACE inhibitors and insulin, as well as hypoglycemic agents for oral administration 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. Patients with diabetes require regular glycemic control, especially during the first month of treatment with ACE inhibitors.

It is recommended to carefully monitor newborns who have been exposed to prenatal ACE inhibitors to detect arterial hypotension, oliguria and hyperkalemia.

In oliguria, it is necessary to maintain blood pressure and renal perfusion by injecting appropriate fluids and vasoconstrictor agents. These newborns are at risk of developing oliguria and neurological disorders, possibly due to a decrease in renal and cerebral blood flow due to a decrease in blood pressure caused by ACE inhibitors.

During therapy with ACE inhibitors, a dry cough may occur. Coughing persists while taking this group of drugs and disappears after they are canceled. When a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom.

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

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

- control of kidney function (determination of serum creatinine). In the treatment of ACE inhibitors in the first weeks of treatment and subsequently recommended to monitor renal function. Especially careful monitoring is required for patients with heart failure, impaired renal function,after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in these patients, even a slight increase in serum creatinine may be an indicator of reduced renal function);

- control of electrolyte content. Regular monitoring of serum potassium is recommended. Particularly careful monitoring of serum potassium is required for patients with impaired renal function, significant impairment of water and electrolyte balance, chronic heart failure;

- control of hematological parameters (hemoglobin content, white blood cell count, red blood cell count, platelet count, leukocyte formula). It is recommended to monitor the indicators of the complete blood count 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 diseases of the connective tissue or in patients receiving at the same time other drugs that can change the pattern of peripheral blood. Control of the number of leukocytes is necessary for early detection of leukopenia, which is especially important in patients with an increased risk of its development, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000 / μl), treatment with ramipril is required.If symptoms arise due to leukopenia (for example, fever, swollen lymph nodes, tonsillitis), urgent monitoring of the peripheral blood pattern is necessary. In the case of signs of bleeding (the smallest petechiae, red-brown lesions on the skin and